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Reis LG, Teeple K, Dinn M, Schoonmaker J, Scinto SB, Ferreira CR, Casey T. Exposure to circadian disrupting environment and high-fat diet during pregnancy and lactation alter reproductive competence and lipid profiles of liver, mammary, plasma and milk of ICR mice. PLoS One 2025; 20:e0320538. [PMID: 40163509 PMCID: PMC11957368 DOI: 10.1371/journal.pone.0320538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 02/21/2025] [Indexed: 04/02/2025] Open
Abstract
This study's objective was to determine the effects of pre-pregnancy obesity induced by a high-fat diet and exposure to circadian-disrupting light-dark phase shifts on birth littler size, pup survival to 24h and growth to lactation day 12, and their relationship to maternal feeding patterns, fecal corticosterone levels, milk composition, and lipid profiles of liver, plasma, mammary gland, and milk. A 2 by 2 factorial designed experiment of female ICR mice assigned to control (CON; 10% fat) or high-fat (HF; 60% fat) and either a 12-hour light-dark (LD) cycle or a chronic jet lag model of 6-hour phase-shifts (PS) in light-dark cycle every 3 days throughout pregnancy and lactation, resulted in 4 treatment groups: CON-LD, CON-PS, HF-LD and HF-PS. HF diet increased maternal pre-pregnancy body weight and elevated milk lactose. Whereas PS reduced milk lactose within the CON diet group, and increased maternal feed intake and fecal corticosterone levels. PS exposure also affected the time of day of birth. Neither PS nor HF affected birth litter size or pup survival. Only diet impacted final litter weight, with HF greater than CON. Among the 1204 lipids detected by multiple reaction monitoring (MRM)-profiling, diet altered 67.1% in milk, 58.1% in mammary gland, 27.2% in the liver, and 10.9% in plasma, with HF increasing the carbon length of diacylglycerols in the liver and milk, and carbon length of triacylglycerols in plasma, mammary gland and milk. Although exposure to PS had no overall impact on maternal lipid profiles, interactions (P < 0.05) were found between PS and diets in the phosphatidylcholine and phosphatidylethanolanine class of lipids. Findings support that high fat diet and exposure to circadian disrupting environments impact maternal feeding behavior and stress responses as well as lipid profiles, which may relate to their negative association with maternal health and offspring development.
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Affiliation(s)
- Leriana Garcia Reis
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Kelsey Teeple
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Michayla Dinn
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Jenna Schoonmaker
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Sara Brook Scinto
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | | | - Theresa Casey
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America
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Miller SJ, Hill K, Darby I, Nusrat F, Friedman JE, Rudolph MC, Zimmerman KA. The impact of maternal obesity on polycystic kidney disease progression in a mouse model. Am J Physiol Renal Physiol 2025; 328:F316-F327. [PMID: 39908005 DOI: 10.1152/ajprenal.00227.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/08/2024] [Accepted: 01/27/2025] [Indexed: 02/06/2025] Open
Abstract
Due to the growing obesity epidemic in the United States, it is now estimated that approximately one third of all children are born to obese moms. These data, coupled with data indicating that obesity is associated with accelerated cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD), led us to hypothesize that maternal obesity may influence the rate of disease progression in offspring. To test this hypothesis, we induced maternal obesity by high-fat diet (HFD) feeding in the orthologous Pkd1RC/RC mouse model of ADPKD and followed polycystic kidney disease (PKD) progression in offspring for up to 1 year. Surprisingly, and in contrast to our initial hypothesis, exposure to maternal obesity during pregnancy and lactation did not significantly impact PKD severity in offspring at 3 mo or 1 yr of age. In contrast, reexposure to HFD for ∼3 m beginning at 12 wk of age worsened PKD severity in female, but not male, offspring born to obese dams as measured by cystic index, cyst number, and cyst area. Despite worsened cystic parameters, fibrosis and blood urea nitrogen were not altered in these animals. Collectively, these findings indicate that maternal obesity may accelerate PKD severity in female offspring exposed to an obesogenic diet.NEW & NOTEWORTHY Due to the growing obesity pandemic, almost one third of all children are born to mothers with obesity; however, the impact of maternal obesity on polycystic kidney disease (PKD) is unknown. In this manuscript, we found that maternal obesity did not worsen PKD severity in Pkd1RC/RC mice at 3 mo or 1 yr of age when weaned onto normal chow diet. However, rechallenging pups born to obese mothers worsened PKD severity in female but not male mice.
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Affiliation(s)
- Sarah J Miller
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Kaitlyn Hill
- Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Isabella Darby
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Fariha Nusrat
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Jacob E Friedman
- Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Michael C Rudolph
- Department of Biochemistry and Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
| | - Kurt A Zimmerman
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
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Dos Santos AAA, Torrezan R, Rodrigues WDNDS, Ribeiro MVG, Ferreira ARO, Peres MNC, Saavedra LPJ, Raposo SR, Almeida DL, Malta A, Mathias PCDF. High-fat diet during lactation, as opposed to during adolescence or gestation, programs cardiometabolic and autonomic dysfunctions in adult offspring. Brain Res 2025; 1849:149354. [PMID: 39603318 DOI: 10.1016/j.brainres.2024.149354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/06/2024] [Accepted: 11/24/2024] [Indexed: 11/29/2024]
Abstract
The Developmental Origins of Health and Disease (DOHaD) concept has been established for three decades. Many studies have shown that, besides pregnancy, other plastic phases (mainly preconception, lactation, and infancy-adolescence) are also sensitive to environmental changes, including nutritional conditions, that can program health or disease later in life. This study compared the susceptibility of the gestation, lactation and adolescence to a high-fat diet (HFD) intervention to program rats into autonomic nervous system imbalance and cardiometabolic dysfunction in adulthood. Four groups of rats were studied: offspring from mothers exposed to a HFD (35% fat) or a standard chow diet (4.5% fat) during gestation (GEST and CONT groups, respectively), offspring from mothers exposed to the HFD during lactation (LAC), and adolescent rats exposed to the HFD (ADOL). Mothers treated during pregnancy exhibited a higher body mass, but nursing mothers presented the highest food energy intake and higher adiposity. Compared to the other groups, the LAC rats showed increased body mass gain, food energy intake, body fat, glucose intolerance and blood pressure. LAC group also showed increased parasympathetic activity. In contrast, LAC sympathetic nerve activity decreased compared with the other groups. The ADOL group exhibited mostly similar responses but of a smaller magnitude. This suggests that the lactation phase is the most sensitive to HFD programming for cardiometabolic dysfunction in adulthood and that early overnutrition may affect neural connections by altering the autonomic nervous system balance.
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Affiliation(s)
- Annie Araújo Alves Dos Santos
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Rosana Torrezan
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | | | - Maiara Vanusa Guedes Ribeiro
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Anna Rebeka Oliveira Ferreira
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Maria Natália Chimirri Peres
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Lucas Paulo Jacinto Saavedra
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Scarlett Rodrigues Raposo
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Douglas Lopes Almeida
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
| | - Ananda Malta
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil.
| | - Paulo Cezar de Freitas Mathias
- Laboratory of Experimental DOHaD, Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá, Maringá 87090-020, Brazil
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Cochrane ALK, Murphy MP, Ozanne SE, Giussani DA. Pregnancy in obese women and mechanisms of increased cardiovascular risk in offspring. Eur Heart J 2024; 45:5127-5145. [PMID: 39508438 DOI: 10.1093/eurheartj/ehae671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/12/2024] [Accepted: 09/19/2024] [Indexed: 11/15/2024] Open
Abstract
Pregnancy complicated by maternal obesity contributes to an increased cardiovascular risk in offspring, which is increasingly concerning as the rates of obesity and cardiovascular disease are higher than ever before and still growing. There has been much research in humans and preclinical animal models to understand the impact of maternal obesity on offspring health. This review summarizes what is known about the offspring cardiovascular phenotype, describing a mechanistic role for oxidative stress, metabolic inflexibility, and mitochondrial dysfunction in mediating these impairments. It also discusses the impact of secondary postnatal insults, which may reveal latent cardiovascular deficits that originated in utero. Finally, current interventional efforts and gaps of knowledge to limit the developmental origins of cardiovascular dysfunction in offspring of obese pregnancy are highlighted.
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Affiliation(s)
- Anna L K Cochrane
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK
| | - Michael P Murphy
- Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK
- MRC Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
| | - Susan E Ozanne
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
- Loke Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Cambridge Strategic Research Initiative in Reproduction, University of Cambridge, Cambridge, UK
- British Heart Foundation, Cambridge Cardiovascular Centre for Research Excellence, University of Cambridge, Cambridge, UK
| | - Dino A Giussani
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
- Loke Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Cambridge Strategic Research Initiative in Reproduction, University of Cambridge, Cambridge, UK
- British Heart Foundation, Cambridge Cardiovascular Centre for Research Excellence, University of Cambridge, Cambridge, UK
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Zhang L, Zhang S, Zou W, Hu Y, Gao Y, Zhang J, Zheng J. Maternal high-fat diet regulates offspring hepatic ABCG5 expression and cholesterol metabolism via the gut microbiota and its derived butyrate. Clin Sci (Lond) 2024; 138:1039-1054. [PMID: 39136693 DOI: 10.1042/cs20240997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 08/24/2024]
Abstract
Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.
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Affiliation(s)
- Ling Zhang
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
| | - Shixuan Zhang
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
| | - Wenyu Zou
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
| | - Yongyan Hu
- Laboratory Animal Facility, Peking University First Hospital, Beijing 100034, China
| | - Ying Gao
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
| | - Junqing Zhang
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
| | - Jia Zheng
- Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
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Skowronski AA, Leibel RL, LeDuc CA. Neurodevelopmental Programming of Adiposity: Contributions to Obesity Risk. Endocr Rev 2024; 45:253-280. [PMID: 37971140 PMCID: PMC10911958 DOI: 10.1210/endrev/bnad031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/29/2023] [Accepted: 10/19/2023] [Indexed: 11/19/2023]
Abstract
This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS-including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity. The in utero and early postnatal periods represent critically sensitive developmental windows during which the hormonal and metabolic milieu affects the maturation of the hypothalamus. Maternal hyperglycemia is associated with increased transfer of glucose to the fetus driving fetal hyperinsulinemia. Elevated fetal insulin causes increased adiposity and consequently higher fetal circulating leptin concentration. Mechanistic studies in animal models indicate important roles of leptin and insulin in central and peripheral programming of adiposity, and suggest that optimal concentrations of these hormones are critical during early life. Additionally, the environmental milieu during development may be conveyed to progeny through epigenetic marks and these can potentially be vertically transmitted to subsequent generations. Thus, nutritional and metabolic/endocrine signals during perinatal development can have lifelong (and possibly multigenerational) impacts on offspring body weight regulation.
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Affiliation(s)
- Alicja A Skowronski
- Division of Molecular Genetics, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA
- Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Rudolph L Leibel
- Division of Molecular Genetics, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA
- Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Charles A LeDuc
- Division of Molecular Genetics, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA
- Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY 10032, USA
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7
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Meulders B, Marei WFA, Xhonneux I, Loier L, Smits A, Leroy JLMR. Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality. Int J Mol Sci 2024; 25:2236. [PMID: 38396912 PMCID: PMC10888670 DOI: 10.3390/ijms25042236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/07/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
Obese individuals often suffer from metabolic health disorders and reduced oocyte quality. Preconception diet interventions in obese outbred mice restore metabolic health and oocyte quality and mitochondrial ultrastructure. Also, studies in inbred mice have shown that maternal obesity induces metabolic alterations and reduces oocyte quality in offspring (F1). Until now, the effect of maternal high-fat diet on F1 metabolic health and oocyte quality and the potential beneficial effects of preconception dietary interventions have not been studied together in outbred mice. Therefore, we fed female mice a high-fat/high-sugar (HF/HS) diet for 7 weeks and switched them to a control (CONT) or caloric-restriction (CR) diet or maintained them on the HF/HS diet for 4 weeks before mating, resulting in three treatment groups: diet normalization (DN), CR, and HF/HS. In the fourth group, mice were fed CONT diet for 11 weeks (CONT). HF/HS mice were fed an HF/HS diet from conception until weaning, while all other groups were then fed a CONT diet. After weaning, offspring were kept on chow diet and sacrificed at 11 weeks. We observed significantly elevated serum insulin concentrations in female HF/HS offspring and a slightly increased percentage of mitochondrial ultrastructural abnormalities, mitochondrial size, and mitochondrial mean gray intensity in HF/HS F1 oocytes. Also, global DNA methylation was increased and cellular stress-related proteins were downregulated in HF/HS F1 oocytes. Mostly, these alterations were prevented in the DN group, while, in CR, this was only the case for a few parameters. In conclusion, this research has demonstrated for the first time that a maternal high-fat diet in outbred mice has a moderate impact on female F1 metabolic health and oocyte quality and that preconception DN is a better strategy to alleviate this compared to CR.
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Affiliation(s)
- Ben Meulders
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
| | - Waleed F. A. Marei
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
- Faculty of Veterinary Medicine, Department of Theriogenology, Cairo University, Giza 12211, Egypt
| | - Inne Xhonneux
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
| | - Lien Loier
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
| | - Anouk Smits
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
| | - Jo L. M. R. Leroy
- Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium; (B.M.); (W.F.A.M.); (I.X.); (L.L.); (A.S.)
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Kweon JY, Mun H, Choi MR, Kim HS, Ahn YJ. Maternal obesity induced metabolic disorders in offspring and myeloid reprogramming by epigenetic regulation. Front Endocrinol (Lausanne) 2024; 14:1256075. [PMID: 38292775 PMCID: PMC10824939 DOI: 10.3389/fendo.2023.1256075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/27/2023] [Indexed: 02/01/2024] Open
Abstract
Maternal obesity and gestational diabetes are associated with childhood obesity and increased cardiovascular risk. In this review, we will discuss and summarize extensive clinical and experimental studies that metabolically imbalanced environment exposure in early life plays a critical role in influencing later susceptibility to chronic inflammatory diseases and metabolic syndrome. The effect of maternal obesity and metabolic disorders, including gestational diabetes cause Large-for-gestational-age (LGA) children to link future development of adverse health issues such as obesity, atherosclerosis, hypertension, and non-alcoholic fatty liver disease by immune reprogramming to adverse micro-environment. This review also addresses intrauterine environment-driven myeloid reprogramming by epigenetic regulations and the epigenetic markers as an underlying mechanism. This will facilitate future investigations regarding maternal-to-fetal immune regulation and the epigenetic mechanisms of obesity and cardiovascular diseases.
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Affiliation(s)
- Joo Young Kweon
- Medical Science and Engineering, Graduate School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Hyeonji Mun
- Medical Science and Engineering, Graduate School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Myeong Ryeol Choi
- Medical Science and Engineering, Graduate School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Hong Seok Kim
- Department of Molecular Medicine, College of Medicine, Inha University, Incheon, Republic of Korea
| | - Yong Joo Ahn
- Medical Science and Engineering, Graduate School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang, Republic of Korea
- Department IT Convergence, Pohang University of Science and Technology, Pohang, Republic of Korea
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9
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Chen Z, Xia LP, Shen L, Xu D, Guo Y, Wang H. Glucocorticoids and intrauterine programming of nonalcoholic fatty liver disease. Metabolism 2024; 150:155713. [PMID: 37914025 DOI: 10.1016/j.metabol.2023.155713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 10/17/2023] [Accepted: 10/20/2023] [Indexed: 11/03/2023]
Abstract
Accumulating epidemiological and experimental evidence indicates that nonalcoholic fatty liver disease (NAFLD) has an intrauterine origin. Fetuses exposed to adverse prenatal environments (e.g., maternal malnutrition and xenobiotic exposure) are more susceptible to developing NAFLD after birth. Glucocorticoids are crucial triggers of the developmental programming of fetal-origin diseases. Adverse intrauterine environments often lead to fetal overexposure to maternally derived glucocorticoids, which can program fetal hepatic lipid metabolism through epigenetic modifications. Adverse intrauterine environments program the offspring's glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis, which contributes to postnatal catch-up growth and disturbs glucose and lipid metabolism. These glucocorticoid-driven programming alterations increase susceptibility to NAFLD in the offspring. Notably, after delivery, offspring often face an environment distinct from their in utero life. The mismatch between the intrauterine and postnatal environments can serve as a postnatal hit that further disturbs the programmed endocrine axes, accelerating the onset of NAFLD. In this review, we summarize the current epidemiological and experimental evidence demonstrating that NAFLD has an intrauterine origin and discuss the underlying intrauterine programming mechanisms, focusing on the role of overexposure to maternally derived glucocorticoids. We also briefly discuss potential early life interventions that may be beneficial against fetal-originated NAFLD.
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Affiliation(s)
- Ze Chen
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Li-Ping Xia
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China
| | - Lang Shen
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China
| | - Dan Xu
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China; Department of Pharmacy, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Yu Guo
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China
| | - Hui Wang
- Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
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10
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Zhang L, Zou W, Hu Y, Wu H, Gao Y, Zhang J, Zheng J. Maternal high-calorie diet feeding programs hepatic cholesterol metabolism and Abca1 promoter methylation in the early life of offspring. J Nutr Biochem 2023; 122:109449. [PMID: 37748622 DOI: 10.1016/j.jnutbio.2023.109449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 07/19/2023] [Accepted: 09/20/2023] [Indexed: 09/27/2023]
Abstract
Maternal high-calorie diet feeding can dramatically increase the susceptibility of metabolic diseases in offspring. However, whether maternal high-calorie diet feeding can program hepatic cholesterol metabolism in the early life of offspring is less understood, and the epigenetic mechanisms underlying this intergenerational effect, especially during the early life of offspring, are unknown. Female C57BL/6J mice were randomly assigned to a high-calorie diet or control diet before and during gestation, and lactation. Lipid metabolism was evaluated in male offspring at weaning. Gene expressions and quantitative methylation levels of key genes associated with hepatic cholesterol metabolism were further evaluated in offspring at weaning age. We found that maternal high-calorie diet feeding resulted in higher body weight, hypercholesterolemia, elevated total cholesterol in liver homogenates, and fat deposits in the liver in offspring at weaning. For key genes that regulate cholesterol metabolism in liver, we showed lower Hmgcr and Ldlr, and higher Abca1 mRNA and protein expressions in offspring from dams fed with high-calorie diet at weaning age. We further found that maternal high-calorie diet feeding significantly decreased Abca1 methylation level in offspring, with lower methylation levels of both CpG 11 and CpG 22 sites. Interestingly, we found that Abca1 methylation level was negatively associated with hepatic Abca1 mRNA expression in offspring from dams fed with high-calorie diet and controls. However, the expressions of key genes associated with hepatic cholesterol metabolism were not significant between fetuses of dams fed with high-calorie diet and control diet. In conclusion, our results indicate that maternal high-calorie diet feeding results in aberrant lipid metabolism, including hypercholesterolemia and fat deposits in the liver of offspring as early as weaning age. Furthermore, maternal high-calorie feeding can program hepatic cholesterol metabolism and Abca1 methylation in the early life of offspring.
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Affiliation(s)
- Ling Zhang
- Department of Endocrinology, Peking University First Hospital, Beijing, China
| | - Wenyu Zou
- Department of Endocrinology, Peking University First Hospital, Beijing, China
| | - Yongyan Hu
- Laboratory Animal Facility, Peking University First Hospital, Beijing, China
| | - Honghua Wu
- Department of Endocrinology, Peking University First Hospital, Beijing, China
| | - Ying Gao
- Department of Endocrinology, Peking University First Hospital, Beijing, China
| | - Junqing Zhang
- Department of Endocrinology, Peking University First Hospital, Beijing, China.
| | - Jia Zheng
- Department of Endocrinology, Peking University First Hospital, Beijing, China.
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11
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Xu Y, Yang D, Wang L, Król E, Mazidi M, Li L, Huang Y, Niu C, Liu X, Lam SM, Shui G, Douglas A, Speakman JR. Maternal High Fat Diet in Lactation Impacts Hypothalamic Neurogenesis and Neurotrophic Development, Leading to Later Life Susceptibility to Obesity in Male but Not Female Mice. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2305472. [PMID: 37867217 PMCID: PMC10724448 DOI: 10.1002/advs.202305472] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Indexed: 10/24/2023]
Abstract
Early life nutrition can reprogram development and exert long-term consequences on body weight regulation. In mice, maternal high-fat diet (HFD) during lactation predisposed male but not female offspring to diet-induced obesity when adult. Molecular and cellular changes in the hypothalamus at important time points are examined in the early postnatal life in relation to maternal diet and demonstrated sex-differential hypothalamic reprogramming. Maternal HFD in lactation decreased the neurotropic development of neurons formed at the embryo stage (e12.5) and impaired early postnatal neurogenesis in the hypothalamic regions of both males and females. Males show a larger increased ratio of Neuropeptide Y (NPY) to Pro-opiomelanocortin (POMC) neurons in early postnatal neurogenesis, in response to maternal HFD, setting an obese tone for male offspring. These data provide insights into the mechanisms by which hypothalamic reprograming by early life overnutrition contributes to the sex-dependent susceptibility to obesity in adult life in mice.
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Affiliation(s)
- Yanchao Xu
- Shenzhen key laboratory for metabolic healthCenter for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055P. R. China
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Dengbao Yang
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Lu Wang
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
- Institute of Biological and Environmental SciencesUniversity of AberdeenAberdeenScotlandAB24 2TZUK
- University of Chinese Academy of SciencesShijingshanBeijing100049P. R. China
- School of PharmacyKey Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantai264005P. R. China
| | - Elżbieta Król
- Institute of Biological and Environmental SciencesUniversity of AberdeenAberdeenScotlandAB24 2TZUK
| | - Mohsen Mazidi
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
- University of Chinese Academy of SciencesShijingshanBeijing100049P. R. China
| | - Li Li
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
- University of Chinese Academy of SciencesShijingshanBeijing100049P. R. China
| | - Yi Huang
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Chaoqun Niu
- Shenzhen key laboratory for metabolic healthCenter for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055P. R. China
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Xue Liu
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Sin Man Lam
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Guanghou Shui
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
| | - Alex Douglas
- Institute of Biological and Environmental SciencesUniversity of AberdeenAberdeenScotlandAB24 2TZUK
| | - John R. Speakman
- Shenzhen key laboratory for metabolic healthCenter for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055P. R. China
- State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101P. R. China
- Institute of Biological and Environmental SciencesUniversity of AberdeenAberdeenScotlandAB24 2TZUK
- China medical universityShenyang110000P. R. China
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12
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Wayland JL, Doll JR, Lawson MJ, Stankiewicz TE, Oates JR, Sawada K, Damen MSMA, Alarcon PC, Haslam DB, Trout AT, DeFranco EA, Klepper CM, Woo JG, Moreno-Fernandez ME, Mouzaki M, Divanovic S. Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases. Nutrients 2023; 15:4958. [PMID: 38068816 PMCID: PMC10708424 DOI: 10.3390/nu15234958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 11/19/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.
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Affiliation(s)
- Jennifer L. Wayland
- Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Jessica R. Doll
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Matthew J. Lawson
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Traci E. Stankiewicz
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Jarren R. Oates
- Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Keisuke Sawada
- Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Michelle S. M. A. Damen
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Pablo C. Alarcon
- Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - David B. Haslam
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
| | - Andrew T. Trout
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
| | - Emily A. DeFranco
- Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
| | - Corie M. Klepper
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Jessica G. Woo
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Maria E. Moreno-Fernandez
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Marialena Mouzaki
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Senad Divanovic
- Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
- Center for Inflammation and Tolerance, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
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13
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Galvan-Martinez DH, Bosquez-Mendoza VM, Ruiz-Noa Y, Ibarra-Reynoso LDR, Barbosa-Sabanero G, Lazo-de-la-Vega-Monroy ML. Nutritional, pharmacological, and environmental programming of NAFLD in early life. Am J Physiol Gastrointest Liver Physiol 2023; 324:G99-G114. [PMID: 36472341 DOI: 10.1152/ajpgi.00168.2022] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.
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Affiliation(s)
| | | | - Yeniley Ruiz-Noa
- Health Sciences Division, Medical Sciences Department, University of Guanajuato, Campus Leon, Mexico
| | | | - Gloria Barbosa-Sabanero
- Health Sciences Division, Medical Sciences Department, University of Guanajuato, Campus Leon, Mexico
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14
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High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life. Br J Nutr 2022:1-10. [PMID: 36412162 DOI: 10.1017/s0007114522003737] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.
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15
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Programming by maternal obesity: a pathway to poor cardiometabolic health in the offspring. Proc Nutr Soc 2022; 81:227-242. [DOI: 10.1017/s0029665122001914] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There is an ever increasing prevalence of maternal obesity worldwide such that in many populations over half of women enter pregnancy either overweight or obese. This review aims to summarise the impact of maternal obesity on offspring cardiometabolic outcomes. Maternal obesity is associated with increased risk of adverse maternal and pregnancy outcomes. However, beyond this exposure to maternal obesity during development also increases the risk of her offspring developing long-term adverse cardiometabolic outcomes throughout their adult life. Both human studies and those in experimental animal models have shown that maternal obesity can programme increased risk of offspring developing obesity and adipose tissue dysfunction; type 2 diabetes with peripheral insulin resistance and β-cell dysfunction; CVD with impaired cardiac structure and function and hypertension via impaired vascular and kidney function. As female offspring themselves are therefore likely to enter pregnancy with poor cardiometabolic health this can lead to an inter-generational cycle perpetuating the transmission of poor cardiometabolic health across generations. Maternal exercise interventions have the potential to mitigate some of the adverse effects of maternal obesity on offspring health, although further studies into long-term outcomes and how these translate to a clinical context are still required.
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16
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Ghnaimawi S, Zhang S, Baum JI, Huang Y. The Effects of Maternal Intake of EPA and DHA Enriched Diet During Pregnancy and Lactation on Offspring's Muscle Development and Energy Homeostasis. Front Physiol 2022; 13:881624. [PMID: 35733999 PMCID: PMC9207413 DOI: 10.3389/fphys.2022.881624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/04/2022] [Indexed: 11/13/2022] Open
Abstract
EPA and DHA are n-3 long-chain polyunsaturated fatty acids with a diversity of health benefits on offspring. The objective of this study was to test the in vivo effect of maternal ingestion of EPA and DHA on fetal and offspring muscle development and energy balance. Two groups of female C57BL/6 mice were fed EPA and DHA enriched diet (FA) and diet devoid of EPA and DHA (CON) respectively throughout the entire period of gestation and lactation. Embryos at E13 and offspring at age of D1 and D21 were selected for sample collection and processing. No change in birth number and body weight were observed between groups at D1 and D21. Transient increase in the expression levels of myogenesis regulating genes was detected at D1 (p < 0.05) in FA group. Most of the expression of muscle protein synthesis regulating genes were comparable (p > 0.05) between FA and CON groups at D1 and D21. The significant increase in MHC4, and IGF-1 was not linked to increased muscle mass. A persistent increase in ISR expression (p < 0.05) but not in GLUT-4 (p > 0.05) was detected in offspring. Up-regulation of adipogenesis regulating genes was accompanied by increasing intramuscular fat accumulation in the offspring of FA group. Considerable increase in transcripts of genes regulating lipid catabolism and thermogenesis in liver (p < 0.05) was noticed in FA group at D21; whereas, only the levels of carnitine palmitoyl transferase 1A (Cpt1α) and Enoyl-CoA Hydratase And 3-Hydroxyacyl CoA Dehydrogenase (Ehhadh) increased at D1. Similarly, genes regulating lipolysis were highly expressed at D21 in FA group. EPA and DHA treatment promoted BAT development and activity by increasing the expression of BAT signature genes (p < 0.05). Also, maternal intake of EPA and DHA enriched diet enhanced browning of sWAT. Taken together, maternal ingestion of EPA/DHA may be suggested as a therapeutic option to improve body composition and counteract childhood obesity- related metabolic disorders and confer lifelong positive metabolic impact on offspring.
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Affiliation(s)
- Saeed Ghnaimawi
- Medical Laboratory Techniques Department, Kut University College, Alkut, Iraq
| | - Shilei Zhang
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Jamie I. Baum
- Department of Food Science, Division of Agriculture, University of Arkansas, Fayetteville, AR, United States
| | - Yan Huang
- Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR, United States
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17
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Han Y, Zhang M, Duan J, Li L, Du J, Cheng H, Zhang S, Zhai Y, An X, Li Q, Zhang X, Li Z, Tang B. Maternal Prepregnancy 5-Hydroxytryptamine Exposure Affects the Early Development of the Fetus. Front Physiol 2022; 13:761357. [PMID: 35370795 PMCID: PMC8969228 DOI: 10.3389/fphys.2022.761357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 01/31/2022] [Indexed: 11/29/2022] Open
Abstract
In recent decades, the increasing incidence of depression has contributed to an increase in the use of serotonergic drugs, such as antidepressants, which predisposes humans to serotonin syndrome. Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. It has been well documented that the development of offspring can be affected by maternal exposure to environmental challenges, such as stress, diseases, or an unhealthy diet during pregnancy. Serotonin, also called 5-hydroxytryptamine (5-HT), is widely expressed in the female reproductive system and plays an important role in the development of follicles and embryos. However, whether the suffering of the mother from serotonin syndrome before pregnancy affects fetal development is still uncertain. In the present study, to explore the effect of maternal prepregnancy 5-HT exposure on the fetus, intraperitoneal injection of 5-HT was used to change maternal prepregnancy 5-HT levels. It was found that maternal prepregnancy 5-HT exposure significantly reduced the body weight and liver weight and the levels of estrogen and progesterone in female mice. Although there was no significant difference in the cleavage rate and blastocyst rate between the 5-HT and control groups, maternal prepregnancy 5-HT exposure increased the percentage of embryo resorption, decreased placental weight, and led to placental inflammation at E13.5. Notably, 5-HT exposure caused weight loss in the offspring at 2 weeks. These results suggested that maternal prepregnancy 5-HT exposure could affect the development of the offspring, which was partly caused by reduced hormonal secretion and placental inflammation.
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Affiliation(s)
- Yu Han
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Meng Zhang
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Jiahui Duan
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Leyi Li
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Jinge Du
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Hui Cheng
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Sheng Zhang
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Yanhui Zhai
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Xinglan An
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Qi Li
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Xueming Zhang
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Ziyi Li
- Academy of Translational Medicine, First Hospital, Jilin University, Changchun, China
| | - Bo Tang
- College of Veterinary Medicine, Jilin University, Changchun, China
- *Correspondence: Bo Tang,
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18
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Ueno M, Liu S, Kiyoi T, Mogi M, Sugiyama T. Long-term impact of maternal dietary intervention on metabolic homeostasis in male offspring in mice. J Nutr Biochem 2022; 104:108971. [DOI: 10.1016/j.jnutbio.2022.108971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 10/10/2021] [Accepted: 01/21/2022] [Indexed: 12/12/2022]
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Kaneko K, Ito Y, Ebara T, Kato S, Matsuki T, Tamada H, Sato H, Saitoh S, Sugiura-Ogasawara M, Yamazaki S, Ohya Y, Kishi R, Yaegashi N, Hashimoto K, Mori C, Ito S, Yamagata Z, Inadera H, Nakayama T, Iso H, Shima M, Kurozawa Y, Suganuma N, Kusuhara K, Katoh T, Kamijima M. Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study. J Clin Endocrinol Metab 2022; 107:e118-e129. [PMID: 34416000 PMCID: PMC8684489 DOI: 10.1210/clinem/dgab618] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Indexed: 12/18/2022]
Abstract
CONTEXT Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS The mean gestational age at blood sampling was 22.7 ± 4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.
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Affiliation(s)
- Kayo Kaneko
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Yuki Ito
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
- Correspondence: Yuki Ito, PhD, Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
| | - Takeshi Ebara
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Sayaka Kato
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Taro Matsuki
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Hazuki Tamada
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Hirotaka Sato
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Shinji Saitoh
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Mayumi Sugiura-Ogasawara
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
| | - Shin Yamazaki
- National Institute for Environmental Studies, Tsukuba 305-8506, Japan
| | - Yukihiro Ohya
- National Center for Child Health and Development, Tokyo 157-0074, Japan
| | - Reiko Kishi
- Hokkaido University, Sapporo 060-0812, Japan
| | | | | | | | - Shuichi Ito
- Yokohama City University, Yokohama 236-0004, Japan
| | | | | | | | | | | | | | | | - Koichi Kusuhara
- University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
| | | | - Michihiro Kamijima
- Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
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20
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Anwer H, Morris MJ, Noble DWA, Nakagawa S, Lagisz M. Transgenerational effects of obesogenic diets in rodents: A meta-analysis. Obes Rev 2022; 23:e13342. [PMID: 34595817 DOI: 10.1111/obr.13342] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 08/11/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022]
Abstract
Obesity is a major health condition that affects millions worldwide. There is an increased interest in understanding the adverse outcomes associated with obesogenic diets. A multitude of studies have investigated the transgenerational impacts of maternal and parental obesogenic diets on subsequent generations of offspring, but results have largely been mixed. We conducted a systematic review and meta-analysis on rodent studies to elucidate how obesogenic diets impact the mean and variance of grand-offspring traits. Our study focused on transgenerational effects (i.e., F2 and F3 generations) in one-off and multigenerational exposure studies. From 33 included articles, we obtained 407 effect sizes representing pairwise comparisons of control and treatment grand-offspring groups pertaining to measures of body weight, adiposity, glucose, insulin, leptin, and triglycerides. We found evidence that male and female grand-offspring descended from grandparents exposed to an obesogenic diet displayed phenotypes consistent with metabolic syndrome, especially in cases where the obesogenic diet was continued across generations. Further, we found stronger evidence for the effects of grand-maternal than grand-paternal exposure on grand-offspring traits. A high-fat diet in one-off exposure studies did not seem to impact phenotypic variation, whereas in multigenerational exposure studies it reduced variation in several traits.
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Affiliation(s)
- Hamza Anwer
- Evolution and Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Margaret J Morris
- School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Daniel W A Noble
- Evolution and Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, Australia
- Division of Ecology and Evolution, Research School of Biology, The Australian National University, Canberra, Australian Capital Territory, Australia
| | - Shinichi Nakagawa
- Evolution and Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Malgorzata Lagisz
- Evolution and Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, Australia
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21
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Aguilera N, Salas-Pérez F, Ortíz M, Álvarez D, Echiburú B, Maliqueo M. Rodent models in placental research. Implications for fetal origins of adult disease. Anim Reprod 2022; 19:e20210134. [PMID: 35493783 PMCID: PMC9037606 DOI: 10.1590/1984-3143-ar2021-0134] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 03/21/2022] [Indexed: 11/22/2022] Open
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22
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Chen Q, Chen H, Wang M, Qiu L, Xi F, Jiang Y, Lv M, Huang HF, Luo Q. The association between alteration of maternal lipid levels and birthweight at term: A within-family comparison. Front Endocrinol (Lausanne) 2022; 13:989663. [PMID: 36246889 PMCID: PMC9562839 DOI: 10.3389/fendo.2022.989663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/16/2022] [Indexed: 11/29/2022] Open
Abstract
CONTEXT Maternal lipid levels affect birthweight and the long-term health of the offsprings. However, this association could be influenced by genetic and other common factors. OBJECTIVE This work aimed to explore the relationship between maternal lipid levels and birthweight of two pregnancies in the same mother. METHODS In this population-based cohort study, 705 women and their 1 410 offsprings were included. From an initial sample of women with more than one singleton birth in the database, we made the following exclusions: missing data for pre-pregnancy BMI, pregnancy weight gain, birthweight and lipid values; maternal age less than 19 or older than 44 years old; gestational age < 37 weeks or > 41weeks, gestational diabetes mellitus/diabetic. In the second and third trimesters, serum samples were collected for the determination of fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Then we assessed the association between maternal lipids and birthweight. RESULTS Infants of women whose 2nd-trimester TC increased by 10th-20th percentile (-0.92~-0.56 mmol/L) from 1st to 2nd pregnancy were 239.69 (62.32~417.06) g lighter at birth than were infants of women those of 40th-50th percentile (-0.20~-0.03 mmol/L). Parity, gestational age, neonatal gender, maternal pre-pregnancy body mass index, maternal weight gain, and 3rd-trimester TC and HDL-C were all associated with higher birth weight. Every unit increase in TC in the third trimester increases birthweight by 53.13 (14.32 ~91.94) g. CONCLUSION Maternal TC level is associated with birthweight independent of shared genes. TC may be used to guide diet and predict birthweight combined with ultrasound and other indicators.
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Affiliation(s)
- Qinqing Chen
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Huiqi Chen
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Minmin Wang
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Liping Qiu
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fangfang Xi
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ying Jiang
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Min Lv
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - He-Feng Huang
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Qiong Luo, ; He-Feng Huang,
| | - Qiong Luo
- Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Qiong Luo, ; He-Feng Huang,
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23
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Grzęda E, Matuszewska J, Ziarniak K, Gertig-Kolasa A, Krzyśko- Pieczka I, Skowrońska B, Sliwowska JH. Animal Foetal Models of Obesity and Diabetes - From Laboratory to Clinical Settings. Front Endocrinol (Lausanne) 2022; 13:785674. [PMID: 35197931 PMCID: PMC8858803 DOI: 10.3389/fendo.2022.785674] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 01/11/2022] [Indexed: 12/26/2022] Open
Abstract
The prenatal period, during which a fully formed newborn capable of surviving outside its mother's body is built from a single cell, is critical for human development. It is also the time when the foetus is particularly vulnerable to environmental factors, which may modulate the course of its development. Both epidemiological and animal studies have shown that foetal programming of physiological systems may alter the growth and function of organs and lead to pathology in adulthood. Nutrition is a particularly important environmental factor for the pregnant mother as it affects the condition of offspring. Numerous studies have shown that an unbalanced maternal metabolic status (under- or overnutrition) may cause long-lasting physiological and behavioural alterations, resulting in metabolic disorders, such as obesity and type 2 diabetes (T2DM). Various diets are used in laboratory settings in order to induce maternal obesity and metabolic disorders, and to alter the offspring development. The most popular models are: high-fat, high-sugar, high-fat-high-sugar, and cafeteria diets. Maternal undernutrition models are also used, which results in metabolic problems in offspring. Similarly to animal data, human studies have shown the influence of mothers' diets on the development of children. There is a strong link between the maternal diet and the birth weight, metabolic state, changes in the cardiovascular and central nervous system of the offspring. The mechanisms linking impaired foetal development and adult diseases remain under discussion. Epigenetic mechanisms are believed to play a major role in prenatal programming. Additionally, sexually dimorphic effects on offspring are observed. Therefore, further research on both sexes is necessary.
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Affiliation(s)
- Emilia Grzęda
- Laboratory of Neurobiology, Faculty of Veterinary Medicine and Animal Science, Poznań University of Life Sciences, Poznań, Poland
| | - Julia Matuszewska
- Laboratory of Neurobiology, Faculty of Veterinary Medicine and Animal Science, Poznań University of Life Sciences, Poznań, Poland
| | - Kamil Ziarniak
- Laboratory of Neurobiology, Faculty of Veterinary Medicine and Animal Science, Poznań University of Life Sciences, Poznań, Poland
- Molecular and Cell Biology Unit, Poznań University of Medical Sciences, Poznań, Poland
| | - Anna Gertig-Kolasa
- Department of Paediatric Diabetes and Obesity, Poznań University of Medical Sciences, Poznań, Poland
| | - Izabela Krzyśko- Pieczka
- Department of Paediatric Diabetes and Obesity, Poznań University of Medical Sciences, Poznań, Poland
| | - Bogda Skowrońska
- Department of Paediatric Diabetes and Obesity, Poznań University of Medical Sciences, Poznań, Poland
| | - Joanna H. Sliwowska
- Laboratory of Neurobiology, Faculty of Veterinary Medicine and Animal Science, Poznań University of Life Sciences, Poznań, Poland
- *Correspondence: Joanna H. Sliwowska,
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Oxidative Stress Profile of Mothers and Their Offspring after Maternal Consumption of High-Fat Diet in Rodents: A Systematic Review and Meta-Analysis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9073859. [PMID: 34868458 PMCID: PMC8636978 DOI: 10.1155/2021/9073859] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 09/27/2021] [Accepted: 10/26/2021] [Indexed: 01/03/2023]
Abstract
Maternal exposure to the high-fat diet (HFD) during gestation or lactation can be harmful to both a mother and offspring. The aim of this systematic review was to identify and evaluate the studies with animal models (rodents) that were exposed to the high-fat diet during pregnancy and/or lactation period to investigate oxidative stress and lipid and liver enzyme profile of mothers and their offspring. The electronic search was performed in the PUBMED (Public/Publisher MEDLINE), EMBASE (Ovid), and Web of Science databases. Data from 77 studies were included for qualitative analysis, and of these, 13 studies were included for meta-analysis by using a random effects model. The pooled analysis revealed higher malondialdehyde levels in offspring of high-fat diet groups. Furthermore, the pooled analysis showed increased reactive oxygen species and lower superoxide dismutase and catalase in offspring of mothers exposed to high-fat diet during pregnancy and/or lactation. Despite significant heterogeneity, the systematic review shows oxidative stress in offspring induced by maternal HFD.
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25
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Huang Y, Osorio Mendoza J, Li M, Jin Z, Li B, Wu Y, Togo J, Speakman JR. Impact of graded maternal dietary fat content on offspring susceptibility to high-fat diet in mice. Obesity (Silver Spring) 2021; 29:2055-2067. [PMID: 34813173 DOI: 10.1002/oby.23270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/19/2021] [Accepted: 07/15/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Maternal high-fat diet (HFD) increases offspring obesity, yet the impacts of different levels of maternal dietary fat have seldom been addressed. In mice, the impact of graded maternal dietary fat on offspring adiposity and offspring's later susceptibility to HFD were assessed. METHODS Lactating mice were fed diets with graded fat content from 8.3% to 66.6%. One male and one female pup from each litter were weaned onto a low-fat diet for 15 weeks. HFD (41.7%) was then introduced to half of the offspring for 12 weeks. RESULTS Offspring body weight and adiposity were positively related to maternal dietary fat content and were higher when mothers were exposed to HFD. The maternal diet effect was nonlinear and sex dependent. A maternal dietary fat of 41.7% and above exaggerated the offspring body weight gain in males but was not significant in females. Maternal 8.3% fat and 25% fat diets led to the highest daily energy expenditure and respiratory exchange ratio in offspring. Offspring fed a low-fat diet had higher daily energy expenditure and respiratory exchange ratio than those fed an HFD. CONCLUSIONS Increasing maternal dietary fat during lactation, and HFD in later life, had significant and interacting impacts on offspring obesity. Maternal diet had a bigger impact on male offspring. The effects of maternal dietary fat content were nonlinear.
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Affiliation(s)
- Yi Huang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | | | - Min Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Zengguang Jin
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- School of Basic Medical Science, Dali University, Dali, Yunnan, China
| | - Baoguo Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Yingga Wu
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jacques Togo
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - John R Speakman
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- School of Biological Sciences, University of Aberdeen, Aberdeen, UK
- Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- CAS Center for Excellence in Animal Evolution and Genetics, Kunming, Yunnan, China
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26
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Francis EC, Dabelea D, Shankar K, Perng W. Maternal diet quality during pregnancy is associated with biomarkers of metabolic risk among male offspring. Diabetologia 2021; 64:2478-2490. [PMID: 34370046 PMCID: PMC8499858 DOI: 10.1007/s00125-021-05533-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/25/2021] [Indexed: 12/30/2022]
Abstract
AIMS/HYPOTHESIS Limited data exist on the association between maternal diet quality during pregnancy and metabolic traits in offspring during early childhood, which is a sensitive period for risk of obesity-related disorders later in life. We aimed to examine the association of maternal diet quality, as indicated by the Healthy Eating Index-2010 (HEI), in pregnancy with offspring metabolic biomarkers and body composition at age 4-7 years. METHODS We used data from 761 mother-offspring pairs from the Healthy Start study to examine sex-specific associations of HEI >57 vs ≤57 with offspring fasting glucose, leptin, cholesterol, HDL, LDL, percentage fat mass, BMI z score and log-transformed insulin, 1/insulin, HOMA-IR, adiponectin, triacylglycerols, triacylglycerols:HDL, fat mass, and sum of skinfolds. Multivariable linear regression models accounted for maternal race/ethnicity, age, education, smoking habits during pregnancy and physical activity, and child's age. RESULTS During pregnancy, mean (SD) HEI score was 55.0 (13.3), and 43.0% had an HEI score >57. Among boys, there was an inverse association of maternal HEI with offspring glucose, insulin, HOMA-IR and adiponectin. For instance, maternal HEI >57 was associated with lower fasting glucose (-0.11; 95% CI -0.20, -0.02 mmol/l), and lower concentrations of: insulin by 15.3% (95% CI -24.6, -5.0), HOMA-IR by 16.3% (95% CI -25.7, -5.6) and adiponectin by 9.3% (95% CI -16.1, -2.0). Among girls, there was an inverse association of maternal HEI with insulin and a positive association with LDL. However, following covariate adjustment, all estimates among girls were attenuated to the null. CONCLUSIONS/INTERPRETATION Greater compliance with the USA Dietary Guidelines via the HEI may improve the maternal-fetal milieu and decrease susceptibility for poor metabolic health among offspring, particularly boys. Future studies are warranted to confirm these associations and determine the underlying mechanisms.
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Affiliation(s)
- Ellen C Francis
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
- Department of Pediatrics, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Kartik Shankar
- Department of Pediatrics, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Wei Perng
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
- Department of Nutritional Sciences, University of Michigan SPH, Ann Arbor, MI, USA
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27
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Li Y, Pollock CA, Saad S. Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition. Genes (Basel) 2021; 12:genes12111653. [PMID: 34828259 PMCID: PMC8624316 DOI: 10.3390/genes12111653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/02/2021] [Accepted: 10/17/2021] [Indexed: 12/13/2022] Open
Abstract
Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring's predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.
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Affiliation(s)
- Yan Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;
| | - Carol A. Pollock
- Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia;
| | - Sonia Saad
- Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia;
- Correspondence:
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Mohammad S, Bhattacharjee J, Vasanthan T, Harris CS, Bainbridge SA, Adamo KB. Metabolomics to understand placental biology: Where are we now? Tissue Cell 2021; 73:101663. [PMID: 34653888 DOI: 10.1016/j.tice.2021.101663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/30/2021] [Accepted: 10/04/2021] [Indexed: 12/16/2022]
Abstract
Metabolomics, the application of analytical chemistry methodologies to survey the chemical composition of a biological system, is used to globally profile and compare metabolites in one or more groups of samples. Given that metabolites are the terminal end-products of cellular metabolic processes, or 'phenotype' of a cell, tissue, or organism, metabolomics is valuable to the study of the maternal-fetal interface as it has the potential to reveal nuanced complexities of a biological system as well as differences over time or between individuals. The placenta acts as the primary site of maternal-fetal exchange, the success of which is paramount to growth and development of offspring during pregnancy and beyond. Although the study of metabolomics has proven moderately useful for the screening, diagnosis, and understanding of the pathophysiology of pregnancy complications, the placental metabolome in the context of a healthy pregnancy remains poorly characterized and understood. Herein, we discuss the technical aspects of metabolomics and review the current literature describing the placental metabolome in human and animal models, in the context of health and disease. Finally, we highlight areas for future opportunities in the emerging field of placental metabolomics.
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Affiliation(s)
- S Mohammad
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - J Bhattacharjee
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - T Vasanthan
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - C S Harris
- Department of Biology & Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada
| | - S A Bainbridge
- Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, ON, Canada
| | - K B Adamo
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada.
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Cao C, Sun S, Li J, Song C, Meng Q, Shi B, Shan A. Lycopene modulates lipid metabolism in rats and their offspring under a high-fat diet. Food Funct 2021; 12:8960-8975. [PMID: 34378595 DOI: 10.1039/d1fo01039e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The purpose of this study was to investigate the effects of lycopene supplementation on lipid metabolism in rats and their offspring. The experiment was conducted on 60 female rats divided into four groups: normal diet, normal diet with 200 mg kg-1 lycopene, high-fat diet, and high-fat diet with 200 mg kg-1 lycopene. The plasma levels of TG, LDL-C, AST and ALT in female rats fed a high-fat diet were significantly increased (P < 0.05). Lycopene supplementation reduced the plasma TG, LEP and AST levels (P < 0.05). In addition, the activity of ACC and mRNA expression of SREBP1c, FAS, PPARγ, CPT1, HMGCR, ACC, PLIN1 and FATP1 in the liver were also increased after feeding a high-fat diet (P < 0.05), whereas the expression of HSL was decreased (P < 0.05). Lycopene increased the activity of HSL and the expression of ATGL in the liver (P < 0.05), and the activity of ACC and mRNA expression of HMGCR and ACC were decreased (P < 0.05). For the offspring, maternal feeding of a high-fat diet reduced the plasma HDL-C levels (P < 0.05), but lycopene supplementation reduced the plasma TC levels (P < 0.05). Maternal high-fat diet also decreased the activity of HSL and the expression of CD36, PLIN1 and FATP1 in the liver while increasing the expression of PPARγ (P < 0.05). Maternal lycopene supplementation decreased the activities of ACC and FAS in the liver and decreased the expression of PPARγ, ACC and PLIN1 (P < 0.05). Maternal feeding of a high-fat diet increased the level of oxidative stress in the liver, the level of blood lipids in plasma and the rate of lipid production in the liver of rats and their offspring. Maternal lycopene supplementation can reduce the level of oxidative stress in rats and their offspring, reduce the level of blood lipids in plasma, and also reduce the rate of lipid production in the liver of rats and offspring.
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Affiliation(s)
- Chunyu Cao
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Shishuai Sun
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Jibo Li
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Chunsheng Song
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Qingwei Meng
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Baoming Shi
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| | - Anshan Shan
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
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Frayre J, Frayre P, Wong I, Mithani A, Bishop S, Mani C, Ponce-Rubio K, Virk R, Morris MJ, Na ES. Perinatal exposure to high fat diet alters expression of MeCP2 in the hypothalamus. Behav Brain Res 2021; 415:113518. [PMID: 34391798 DOI: 10.1016/j.bbr.2021.113518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 07/30/2021] [Accepted: 08/06/2021] [Indexed: 11/27/2022]
Abstract
Obesity is a complex disease that is the result of a number of different factors including genetic, environmental, and endocrine abnormalities. Given that monogenic forms of obesity are rare, it is important to identify other mechanisms that contribute to its etiology. Methyl-Cp-G binding protein 2 (MeCP2) is a neuroepigenetic factor that binds to methylated regions of DNA to influence transcription. Past studies demonstrate that disruption in MeCP2 function produces obesity in mice. Using a diet-induced obesity mouse model, we show that perinatal exposure to high fat diet significantly decreases MeCP2 protein expression in the hypothalamus of female mice, effects not seen when high fat diet is given to mice during adulthood. Moreover, these effects are seen specifically in a subregion of the hypothalamus known as the arcuate nucleus with females having decreased MeCP2 expression in rostral areas and males having decreased MeCP2 expression in intermediate regions of the arcuate nucleus. Interestingly, mice gain more weight when exposed to high fat diet during adulthood relative to mice exposed to high fat diet perinatally, suggesting that perhaps high fat diet exposure during adulthood may be affecting mechanisms independent of MeCP2 function. Collectively, our data demonstrate that there are developmentally sensitive periods in which MeCP2 expression is influenced by high fat diet exposure and this occurs in a sexually dimorphic manner.
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Affiliation(s)
- Jessica Frayre
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Priscila Frayre
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Ida Wong
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Anusha Mithani
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Stephanie Bishop
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Chelsy Mani
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Karen Ponce-Rubio
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Ruvaid Virk
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Michael J Morris
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
| | - Elisa S Na
- Department of Psychology & Philosophy, Texas Woman's University, 304 Administration Dr., Denton, TX, USA.
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Kislal S, Jin W, Maesner C, Edlow AG. Mismatch between obesogenic intrauterine environment and low-fat postnatal diet may confer offspring metabolic advantage. Obes Sci Pract 2021; 7:450-461. [PMID: 34401203 PMCID: PMC8346367 DOI: 10.1002/osp4.501] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 01/25/2021] [Accepted: 02/19/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Mismatch between a depleted intrauterine environment and a substrate-rich postnatal environment confers an increased risk of offspring obesity and metabolic syndrome. Maternal diet-induced obesity (MATOB) is associated with the same outcomes. These experiments tested the hypothesis that a mismatch between a nutrient-rich intrauterine environment and a low-fat postnatal environment would ameliorate offspring metabolic morbidity. METHODS C57BL6/J female mice were fed either a 60% high-fat diet (HFD) or a 10% fat control diet (CD) for 14-week pre-breeding and during pregnancy/lactation. Offspring were weaned to CD. Weight was evaluated weekly; body composition was determined using EchoMRI. Serum fasting lipids and glucose and insulin tolerance tests were performed. Metabolic rate, locomotor, and sleep behavior were evaluated with indirect calorimetry. RESULTS MATOB-exposed/CD-weaned offspring of both sexes had improved glucose tolerance and insulin sensitivity compared to controls. Males had improved fasting lipids. Females had significantly increased weight and body fat percentage in adulthood compared to sex-matched controls. Females also had significantly increased sleep duration and reduced locomotor activity compared to males. CONCLUSIONS Reduced-fat dietary switch following intrauterine and lactational exposure to MATOB was associated with improved glucose handling and lipid profiles in adult offspring, more pronounced in males. A mismatch between a high-fat prenatal and low-fat postnatal environment may confer a metabolic advantage. The amelioration of deleterious metabolic programming by strict offspring adherence to a low-fat diet may have translational potential.
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Affiliation(s)
- Sezen Kislal
- Vincent Center for Reproductive BiologyMassachusetts General HospitalBostonMassachusettsUSA
| | - William Jin
- Vincent Center for Reproductive BiologyMassachusetts General HospitalBostonMassachusettsUSA
| | - Claire Maesner
- Vincent Center for Reproductive BiologyMassachusetts General HospitalBostonMassachusettsUSA
| | - Andrea G. Edlow
- Vincent Center for Reproductive BiologyMassachusetts General HospitalBostonMassachusettsUSA
- Department of Obstetrics and GynecologyMassachusetts General HospitalBostonMassachusettsUSA
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Shrestha A, Prowak M, Berlandi-Short VM, Garay J, Ramalingam L. Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring. Front Cardiovasc Med 2021; 8:696812. [PMID: 34368253 PMCID: PMC8333710 DOI: 10.3389/fcvm.2021.696812] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 06/07/2021] [Indexed: 12/13/2022] Open
Abstract
Maternal obesity has many implications for offspring health that persist throughout their lifespan that include obesity and cardiovascular complications. Several different factors contribute to obesity and they encompass interplay between genetics and environment. In the prenatal period, untreated obesity establishes a foundation for a myriad of symptoms and negative delivery experiences, including gestational hypertensive disorders, gestational diabetes, macrosomia, and labor complications. However, data across human and animal studies show promise that nutritional interventions and physical activity may rescue much of the adverse effects of obesity on offspring metabolic health. Further, these maternal interventions improve the health of the offspring by reducing weight gain, cardiovascular disorders, and improving glucose tolerance. Mechanisms from animal studies have also been proposed to elucidate the signaling pathways that regulate inflammation, lipid metabolism, and oxidative capacity of the tissue, ultimately providing potential specific courses of treatment. This review aims to pinpoint the risks of maternal obesity and provide plausible intervention strategies. We delve into recent research involving both animal and human studies with maternal interventions. With the increasing concerning of obesity rates witnessed in the United States, it is imperative to acknowledge the long-term effects posed on future generations and specifically modify maternal nutrition and care to mitigate these adverse outcomes.
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Affiliation(s)
- Akriti Shrestha
- Department of Nutrition and Food Studies, Syracuse University, Syracuse, NY, United States
| | - Madison Prowak
- Department of Nutrition and Food Studies, Syracuse University, Syracuse, NY, United States
| | | | - Jessica Garay
- Department of Nutrition and Food Studies, Syracuse University, Syracuse, NY, United States
| | - Latha Ramalingam
- Department of Nutrition and Food Studies, Syracuse University, Syracuse, NY, United States
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Sekkarie A, Welsh JA, Northstone K, Stein AD, Ramakrishnan U, Vos MB. Associations of maternal diet and nutritional status with offspring hepatic steatosis in the Avon longitudinal study of parents and children. BMC Nutr 2021; 7:28. [PMID: 34233762 PMCID: PMC8265091 DOI: 10.1186/s40795-021-00433-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/22/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Priming for cardiometabolic diseases, including non-alcoholic fatty liver disease (NAFLD), is hypothesized to begin in utero. The primary objective of this study is to determine whether there is an association between maternal nutritional status and offspring NAFLD. METHODS Data come from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK. The analytic sample included 3353 participants who had maternal information on pre-pregnancy BMI, gestational weight gain, diabetes, and free sugar intake as percent of total energy and were assessed for mild-severe hepatic steatosis at 24 years by transient elastography (controlled attenuation parameter score ≥ 248 dB/m). Multiple logistic regression was used to evaluate the association between maternal factors and offspring hepatic steatosis at 24 years. RESULTS In confounder-adjusted models the independent associations for each maternal factor with mild to severe vs low hepatic steatosis at 24 years were: pre-pregnancy overweight (OR: 1.84, 95%CL: 1.43-2.38) or obesity (OR: 2.73, 95%CL: 1.84-4.03), more than recommended gestational weight gain (OR: 1.30, 95%CL: 1.04-1.64), diabetes (OR: 1.39, 95%CI: 0.87, 2.21), and high free sugar intake during pregnancy (OR: 1.04, 95% CI: 0.82, 1.33). These associations were largely mediated by BMI at 24 years, but not by birthweight or breastfeeding. CONCLUSIONS Our results suggest that maternal nutritional status is associated with the development of NAFLD in their adult offspring, although the relationship is largely mediated by offspring BMI in adulthood.
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Affiliation(s)
- Ahlia Sekkarie
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, 1518 Clifton Rd NE, Atlanta, GA, 30322, USA.
| | - Jean A Welsh
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, 1518 Clifton Rd NE, Atlanta, GA, 30322, USA
- Department of Pediatrics, Emory School of Medicine, Atlanta, GA, 30322, USA
| | - Kate Northstone
- Population Health Science, Bristol Medical School, Bristol, BS8 2BN, UK
| | - Aryeh D Stein
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, 1518 Clifton Rd NE, Atlanta, GA, 30322, USA
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA
| | - Usha Ramakrishnan
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA
| | - Miriam B Vos
- Department of Pediatrics, Emory School of Medicine, Atlanta, GA, 30322, USA
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Zimmerman B, Kundu P, Rooney WD, Raber J. The Effect of High Fat Diet on Cerebrovascular Health and Pathology: A Species Comparative Review. Molecules 2021; 26:3406. [PMID: 34199898 PMCID: PMC8200075 DOI: 10.3390/molecules26113406] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/19/2021] [Accepted: 06/01/2021] [Indexed: 02/08/2023] Open
Abstract
In both humans and animal models, consumption of a high-saturated-fat diet has been linked to vascular dysfunction and cognitive impairments. Laboratory animals provide excellent models for more invasive high-fat-diet-related research. However, the physiological differences between humans and common animal models in terms of how they react metabolically to high-fat diets need to be considered. Here, we review the factors that may affect the translatability of mechanistic research in animal models, paying special attention to the effects of a high-fat diet on vascular outcomes. We draw attention to the dissociation between metabolic syndrome and dyslipidemia in rodents, unlike the state in humans, where the two commonly occur. We also discuss the differential vulnerability between species to the metabolic and vascular effects of macronutrients in the diet. Findings from animal studies are better interpreted as modeling specific aspects of dysfunction. We conclude that the differences between species provide an opportunity to explore why some species are protected from the detrimental aspects of high-fat-diet-induced dysfunction, and to translate these findings into benefits for human health.
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Affiliation(s)
- Benjamin Zimmerman
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; (B.Z.); (P.K.); (W.D.R.)
- Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Payel Kundu
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; (B.Z.); (P.K.); (W.D.R.)
| | - William D. Rooney
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; (B.Z.); (P.K.); (W.D.R.)
- Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA
| | - Jacob Raber
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; (B.Z.); (P.K.); (W.D.R.)
- Departments of Neurology and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA
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Peleg-Raibstein D. Understanding the Link Between Maternal Overnutrition, Cardio-Metabolic Dysfunction and Cognitive Aging. Front Neurosci 2021; 15:645569. [PMID: 33716660 PMCID: PMC7953988 DOI: 10.3389/fnins.2021.645569] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 02/10/2021] [Indexed: 12/16/2022] Open
Abstract
Obesity has long been identified as a global epidemic with major health implications such as diabetes and cardiovascular disease. Maternal overnutrition leads to significant health issues in industrial countries and is one of the risk factors for the development of obesity and related disorders in the progeny. The wide accessibility of junk food in recent years is one of the major causes of obesity, as it is low in nutrient content and usually high in salt, sugar, fat, and calories. An excess of nutrients during fetal life not only has immediate effects on the fetus, including increased growth and fat deposition in utero, but also has long-term health consequences. Based on human studies, it is difficult to discern between genetic and environmental contributions to the risk of disease in future generations. Consequently, animal models are essential for studying the impact of maternal overnutrition on the developing offspring. Recently, animal models provided some insight into the physiological mechanisms that underlie developmental programming. Most of the studies employed thus far have focused only on obesity and metabolic dysfunctions in the offspring. These studies have advanced our understanding of how maternal overnutrition in the form of high-fat diet exposure can lead to an increased risk of obesity in the offspring, but many questions remain open. How maternal overnutrition may increase the risk of developing brain pathology such as cognitive disabilities in the offspring and increase the risk to develop metabolic disorders later in life? Further, does maternal overnutrition exacerbate cognitive- and cardio-metabolic aging in the offspring?
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Affiliation(s)
- Daria Peleg-Raibstein
- Laboratory of Neurobehavioural Dynamics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland
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Rosales-Nieto CA, Ehrhardt R, Mantey A, Makela B, Veiga-Lopez A. Preconceptional diet manipulation and fetus number can influence placenta endocrine function in sheep. Domest Anim Endocrinol 2021; 74:106577. [PMID: 33160155 PMCID: PMC7719092 DOI: 10.1016/j.domaniend.2020.106577] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 01/21/2023]
Abstract
Changes in maternal nutrition during pregnancy can result in profound effects on placental function and fetal development. Although the preconceptional period holds the potential to reprogram embryonic and placental development, little is known regarding the effects of premating nutritional manipulation on placental function and fetal and postnatal offspring growth. To test this, Polypay-Dorset sheep (n = 99) were assigned to 1 of 3 nutritional treatments (n = 33/treatment) receiving 50% (UN: undernutrition), 100% (C: control), or 200% (ON: overnutrition) of maintenance energy requirements for 21 d before mating during April-May (increasing photoperiod). Thereafter, diets were the same across groups. We evaluated maternal reproductive variables and maternal and offspring weight and body mass index through weaning. Maternal plasma was collected through pregnancy until postnatal day 1 to assay pregnancy-associated glycoproteins (PAGs) and progesterone. Fertility rate was similar among treatments, but ON females had a higher reproductive rate (UN: 82%; C: 100%, ON: 145%). When correcting by total birth weight, twin pregnancies had lower PAGs and progesterone versus singleton pregnancies (P < 0.001). At birth, UN lambs were heavier than C lambs regardless of birth type (P < 0.01). Growth velocity, daily gain, and weaning weight were similar, but UN and ON females grew faster and were heavier at weaning versus C females. We demonstrated that a 3-wk preconceptional maternal undernutrition or overnutrition, when correcting by total birth weight, results in lower endocrine capacity in twin pregnancies. Preconceptional maternal undernutrition and overnutrition increased postnatal female lamb growth, suggestive of reprogramming of pathways regulating growth before conception. This highlights how preconceptional nutrition can result in marked sex-specific differences.
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Affiliation(s)
- C A Rosales-Nieto
- Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA
| | - R Ehrhardt
- Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA; Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - A Mantey
- Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA
| | - B Makela
- Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA
| | - A Veiga-Lopez
- Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA; Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
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Easton ZJW, Regnault TRH. The Impact of Maternal Body Composition and Dietary Fat Consumption upon Placental Lipid Processing and Offspring Metabolic Health. Nutrients 2020; 12:nu12103031. [PMID: 33022934 PMCID: PMC7601624 DOI: 10.3390/nu12103031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/20/2022] Open
Abstract
The proportion of women of reproductive age who are overweight or obese is increasing globally. Gestational obesity is strongly associated in both human studies and animal models with early-onset development of adult-associated metabolic diseases including metabolic syndrome in the exposed offspring. However, animal model studies have suggested that gestational diet in obese pregnancies is an independent but underappreciated mediator of offspring risk for later life metabolic disease, and human diet consumption data have highlighted that many women do not follow nutritional guidelines prior to and during pregnancy. Thus, this review will highlight how maternal diet independent from maternal body composition impacts the risk for later-life metabolic disease in obesity-exposed offspring. A poor maternal diet, in combination with the obese metabolic state, are understood to facilitate pathological in utero programming, specifically through changes in lipid handling processes in the villous trophoblast layer of the placenta that promote an environment associated with the development of metabolic disease in the offspring. This review will additionally highlight how maternal obesity modulates villous trophoblast lipid processing functions including fatty acid transport, esterification and beta-oxidation. Further, this review will discuss how altering maternal gestational diet may ameliorate these functional changes in lipid metabolic processes in the obese placenta.
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Affiliation(s)
- Zachary J. W. Easton
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada;
- Correspondence: ; Tel.: +1-(519)-661-2111 (ext. 82869)
| | - Timothy R. H. Regnault
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada;
- Department of Obstetrics and Gynaecology, London Health Science Centre-Victoria Hospital, B2-401, London, ON N6H 5W9, Canada
- Children’s Health Research Institute, 800 Commissioners Road East, London, ON N6C 2V5, Canada
- Lawson Health Research Institute, 750 Base Line Rd E, London, ON N6C 2R5, Canada
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Kislal S, Shook LL, Edlow AG. Perinatal exposure to maternal obesity: Lasting cardiometabolic impact on offspring. Prenat Diagn 2020; 40:1109-1125. [PMID: 32643194 DOI: 10.1002/pd.5784] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 06/25/2020] [Accepted: 07/05/2020] [Indexed: 12/11/2022]
Abstract
Evidence from epidemiological, clinical, and animal model studies clearly demonstrates that prenatal and lactational maternal obesity and high-fat diet consumption are associated with cardiometabolic morbidity in offspring. Fetal and offspring sex may be an important effect modifier. Adverse offspring cardiometabolic outcomes observed in the setting of maternal obesity include an increased risk for obesity, features of metabolic syndrome (hypertension, hyperglycemia and insulin resistance, hyperlipidemia, increased adiposity), and non-alcoholic fatty liver disease. This review article synthesizes human and animal data linking maternal obesity and high-fat diet consumption in pregnancy and lactation to adverse cardiometabolic outcomes in offspring. We review key mechanisms underlying skeletal muscle, adipose tissue, pancreatic, liver, and central brain reward programming in obesity-exposed offspring, and how such malprogramming contributes to offspring cardiometabolic morbidity.
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Affiliation(s)
- Sezen Kislal
- Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lydia L Shook
- Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrea G Edlow
- Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Maternal obesity: focus on offspring cardiometabolic outcomes. INTERNATIONAL JOURNAL OF OBESITY SUPPLEMENTS 2020; 10:27-34. [PMID: 32714510 DOI: 10.1038/s41367-020-0016-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Several human and animal studies have demonstrated that cardiometabolic parameters in infancy, childhood, adolescence and even adulthood are negatively influenced by many factors besides energy imbalance. Interestingly, maternal weight excess both before and during pregnancy seems to be a negative determinant of metabolic and cardiovascular outcomes in the offspring. This review includes both human and animal studies and finally highlights the link between maternal obesity and cardiometabolic disorders in offspring.
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Heinecke F, Mazzucco MB, Fornes D, Roberti S, Jawerbaum A, White V. The offspring from rats fed a fatty diet display impairments in the activation of liver peroxisome proliferator activated receptor alpha and features of fatty liver disease. Mol Cell Endocrinol 2020; 511:110818. [PMID: 32298755 DOI: 10.1016/j.mce.2020.110818] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 02/06/2023]
Abstract
Maternal obesity programs liver derangements similar to those of NAFLD. Our main goal was to evaluate whether these liver anomalies were related to aberrant PPARα function. Obesity was induced in female Albino-Wistar rats by a fatty diet (FD rats). Several parameters related to NAFLD were evaluated in both plasma and livers from fetuses of 21 days of gestation and 140-day-old offspring. FD fetuses and offspring developed increased levels of AST and ALT, signs of inflammation and oxidative and nitrative stress-related damage. FD offspring showed dysregulation of Plin2, CD36, Cyp4A, Aco, Cpt-1, Hadha and Acaa2 mRNA levels, genes involved in lipid metabolism and no catabolic effect of the PPARα agonist clofibrate. These results suggest that the FD offspring is prone to develop fatty liver, a susceptibility that can be linked to PPARα dysfunction, and that this could in turn be related to the liver impairments programmed by maternal obesity.
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Affiliation(s)
- Florencia Heinecke
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina
| | - María Belén Mazzucco
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina
| | - Daiana Fornes
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina
| | - Sabrina Roberti
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina
| | - Alicia Jawerbaum
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina
| | - Verónica White
- Laboratory of Reproduction and Metabolism, Centre for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine University of Buenos Aires, Argentina.
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Gawlińska K, Gawliński D, Filip M, Przegaliński E. Relationship of maternal high-fat diet during pregnancy and lactation to offspring health. Nutr Rev 2020; 79:709-725. [PMID: 32447401 DOI: 10.1093/nutrit/nuaa020] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
A balanced maternal diet is essential for proper fetal development, and the consumption of a nutritionally inadequate diet during intrauterine development and early childhood is associated with a significantly increased risk of metabolic and brain disorders in offspring. The current literature indicates that maternal exposure to a high-fat diet exerts an irreversible influence on the general health of the offspring. This review of preclinical research examines the relationship between a maternal high-fat diet during pregnancy or lactation and metabolic changes, molecular alterations in the brain, and behavioral disorders in offspring. Animal models indicate that offspring exposed to a maternal high-fat diet during pregnancy and lactation manifest increased depressive-like and aggressive behaviors, reduced cognitive development, and symptoms of metabolic syndrome. Recently, epigenetic and molecular studies have shown that maternal nutrition during pregnancy and the suckling period modifies the development of neurotransmitter circuits and many other factors important to central nervous system development. This finding confirms the importance of a balanced maternal diet for the health of offspring.
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Affiliation(s)
- Kinga Gawlińska
- Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
| | - Dawid Gawliński
- Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
| | - Małgorzata Filip
- Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
| | - Edmund Przegaliński
- Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
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Wada N, Yamada H, Motoyama S, Saburi M, Sugimoto T, Kubota H, Miyawaki D, Wakana N, Kami D, Ogata T, Matoba S. Maternal high-fat diet exaggerates diet-induced insulin resistance in adult offspring by enhancing inflammasome activation through noncanonical pathway of caspase-11. Mol Metab 2020; 37:100988. [PMID: 32272237 PMCID: PMC7210595 DOI: 10.1016/j.molmet.2020.100988] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 03/22/2020] [Accepted: 03/31/2020] [Indexed: 02/06/2023] Open
Abstract
Objective Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. Methods Eight-week-old female wild-type mice (C57BL/6) were fed either an HFD or a normal diet (ND), one week prior to mating, and the diet was continued throughout gestation and lactation. Eight-week-old male offspring of both groups were fed an HFD for 8 weeks. Results Offspring of HFD-fed dams (O-HFD) exhibited significantly impaired insulin sensitivity compared with the offspring of ND-fed dams (O-ND). The adipocyte size of the eWAT increased significantly in O-HFD and was accompanied by abundant crown-like structures (CLSs), as well as a higher concentration of interleukin 1β (IL-1β) in the eWAT. Treatment with an inflammasome inhibitor, MCC950, completely abrogated the enhanced IR in O-HFD. However, ex vivo caspase-1 activity in eWAT revealed no difference between the two groups. In contrast, noncanonical inflammasome activation of caspase-11 was significantly augmented in O-HFD compared with O-ND, suggesting that membrane pore formation, but not cleavage of pro-IL-1β by caspase-1, is augmented in O-HFD. To examine the membrane pore formation, we performed metabolic activation of bone marrow-derived macrophages (BMDMs). The percentage of pore formation assessed by ethidium bromide staining was significantly higher in BMDMs of O-HFD, accompanied by an enhanced active caspase-11 expression. Consistently, the concentration of IL-1β in culture supernatants was significantly higher in the BMDMs from O-HFD than those from O-ND. Conclusions These findings demonstrate that maternal HFD exaggerates diet-induced IR in adult offspring by enhancing noncanonical caspase-11-mediated inflammasome activation.
Maternal HFD increases the vulnerability to HFD-induced IR in adult offspring. Maternal HFD augments inflammasome activation in eWAT in adult offspring. Treatment with an inflammasome inhibitor abrogates IR in offspring of HFD-fed dam. Maternal HFD augments the noncanonical inflammasome activation pathway of caspase-11. Maternal HFD augments IL-1β release from BMDMs by enhancing membrane pore formation.
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Affiliation(s)
- Naotoshi Wada
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroyuki Yamada
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Shinichiro Motoyama
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Makoto Saburi
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Sugimoto
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Kubota
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Daisuke Miyawaki
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Noriyuki Wakana
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Daisuke Kami
- Department of Regenerative Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takehiro Ogata
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoaki Matoba
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers. Cells 2020; 9:cells9040791. [PMID: 32218167 PMCID: PMC7226525 DOI: 10.3390/cells9040791] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/19/2020] [Accepted: 03/23/2020] [Indexed: 12/20/2022] Open
Abstract
Maternal obesity impacts offspring metabolism. We sought to boost mitochondrial energy metabolism using the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) to treat metabolic impairment induced by maternal and long-term post weaning over-nutrition. Male offspring of lean or obese mothers, fed chow or high fat diet (HFD) for 30 weeks post-weaning, were given NMN injection, starting at 31 weeks of age, daily for 3 weeks before sacrifice. Glucose tolerance was tested at 10, 29 and 32 weeks of age to measure short and long term effects of post-weaning HFD, and NMN treatment. Plasma insulin and triglycerides, liver triglycerides and expression of mitochondrial metabolism-related genes were measured at 34 weeks. Impaired glucose tolerance due to maternal and post weaning HFD was significantly improved by only 8 days of NMN treatment. Furthermore, in offspring of obese mothers hepatic lipid accumulation was reduced due to NMN treatment by 50% and 23% in chow and HFD fed offspring respectively. Hepatic genes involved in fat synthesis, transport and uptake were reduced, while those involved in fatty acid oxidation were increased by NMN. Overall this finding suggests short term administration of NMN could be a therapeutic approach for treating metabolic disease due to maternal and post weaning over-nutrition, even in late adulthood.
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Kruse M, Keyhani-Nejad F, Osterhoff MA, Pfeiffer AFH. Sexually dimorphic metabolic responses to exposure of a high fat diet during pregnancy, lactation and early adulthood in Gipr -/- mice. Peptides 2020; 125:170250. [PMID: 31917165 DOI: 10.1016/j.peptides.2019.170250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 12/22/2019] [Accepted: 12/26/2019] [Indexed: 12/25/2022]
Abstract
Obesity has a multifactorial origin. It is known that alterations of the intra uterine milieu induce developmental programming effects leading to metabolic diseases in offspring. Obesity is diminished in mice lacking the glucose-dependent insulinotropic polypeptide receptor (Gipr-/-) when exposed to a high fat diet (HFD). We investigated whether Gipr-/- mice are still protected from obesity when additionally exposure to a HFD during pregnancy and lactation occurs. Male and female wild type (WT) and Gipr-/- offspring received either a control/ low fat diet or HFD during pregnancy and lactation and were then either left on this diet or placed on the opposite diet after weaning until 24 weeks of life. Female WT mice showed increased body weight and adiposity when exposed to a HFD during pregnancy and lactation and post-weaning compared to female WT that received the HFD after weaning only. This exacerbated effect of a HFD during pregnancy and lactation was abolished in female Gipr-/- mice. Male Gipr-/- mice were protected from obesity to a much lesser extent. Male Gipr-/- mice exposed to a HFD during pregnancy and lactation and after weaning exhibited significantly increased fed serum glucose compared to Gipr-/- mice exposed to a HFD after weaning only. In female Gipr-/- mice no differences in fed blood glucose were observed between these groups. Our data indicate that female Gipr-/- mice are more protected from obesity. This protection is preserved in female Gipr-/- mice when additional deleterious effects of a HFD occur during fetal development.
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Affiliation(s)
- Michael Kruse
- Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charité - University of Medicine, Hindenburgdamm 30, 12200 Berlin, Germany
| | - Farnaz Keyhani-Nejad
- Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charité - University of Medicine, Hindenburgdamm 30, 12200 Berlin, Germany
| | - Martin A Osterhoff
- Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charité - University of Medicine, Hindenburgdamm 30, 12200 Berlin, Germany
| | - Andreas F H Pfeiffer
- Department of Clinical Nutrition, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charité - University of Medicine, Hindenburgdamm 30, 12200 Berlin, Germany; German Center for Diabetes Research, Germany.
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Chen HC, Chen YZ, Wang CH, Lin FJ. The nonalcoholic fatty liver disease-like phenotype and lowered serum VLDL are associated with decreased expression and DNA hypermethylation of hepatic ApoB in male offspring of ApoE deficient mothers fed a with Western diet. J Nutr Biochem 2019; 77:108319. [PMID: 31926452 DOI: 10.1016/j.jnutbio.2019.108319] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 11/13/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023]
Abstract
Increasing evidence indicates that the intra-uterine environment has consequences for later life. However, the mechanisms of this fetal programming remain unclear. We aimed to investigate the impact of diet-induced maternal hypercholesterolemia on the predisposition of offspring to nonalcoholic fatty liver diseases (NAFLD) and metabolic diseases and its underlying mechanisms. Female apolipoprotein (Apo) E-deficient mice were fed a control diet (CD) or high fat/high cholesterol Western-type diet (WD) before and throughout pregnancy and lactation, and their offspring were weaned onto a CD postnatally. Strikingly, male offspring of WD-fed dams developed glucose intolerance and decreased peripheral insulin sensitivity and exhibited hepatic steatosis. Hepatic steatosis could be attributed, at least in part, to increased hepatic lipogenesis in E18.5 embryos and decreased serum VLDL levels in adulthood. In addition, males born to WD-fed dams had lower serum ApoB levels and hepatic ApoB gene expression compared with males born to CD-fed dams. DNA methylation analysis revealed increased methylation of CpG dinucleotides on the promoter region of the ApoB genes in the livers of male offspring of WD-fed dams. Our findings suggest that maternal WD intake can exacerbate the development of NAFLD in male offspring potentially by affecting ApoB gene expression through epigenetic alterations.
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Affiliation(s)
- Hsiao-Chien Chen
- Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Yi-Zhen Chen
- Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Chih-Hong Wang
- Department of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan
| | - Fu-Jung Lin
- Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan; Research Center for Development Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
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Wang XF, Li JD, Huo YL, Zhang YP, Fang ZQ, Wang HP, Peng W, Johnson AK, Xue B. Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring. Am J Physiol Regul Integr Comp Physiol 2019; 318:R351-R359. [PMID: 31746626 DOI: 10.1152/ajpregu.00200.2019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.
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Affiliation(s)
- Xue-Fang Wang
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Jian-Dong Li
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Yan-Li Huo
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Yu-Ping Zhang
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Zhi-Qin Fang
- First Affiliated Hospital, Hebei North University, Zhangjiakou City, China
| | - Hai-Ping Wang
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Wei Peng
- Life Science Research Center, Hebei North University, Zhangjiakou City, China
| | - Alan Kim Johnson
- Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa
| | - Baojian Xue
- Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa
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Abais-Battad JM, Lund H, Fehrenbach DJ, Dasinger JH, Alsheikh AJ, Mattson DL. Parental Dietary Protein Source and the Role of CMKLR1 in Determining the Severity of Dahl Salt-Sensitive Hypertension. Hypertension 2019; 73:440-448. [PMID: 30595125 DOI: 10.1161/hypertensionaha.118.11994] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Studies from our laboratory have revealed an important role for the maternal diet and the dietary protein source in the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats. The current study sought to compare salt-induced hypertension, renal damage, and immune cell infiltration in the offspring of breeders fed either a casein- or gluten-based diet, with the hypothesis that offspring from gluten-fed breeders would fail to develop these SS phenotypes. When fed identical diets post-weaning, the F1 generation gluten offspring demonstrated lower mean arterial pressure (149.1±3.1 versus 162.5±5.8 mm Hg), albuminuria (166.2±34.6 versus 250.9±27.8 mg/day), and outer medullary protein casting (7.4±0.8% versus 13.1±1.3%) in response to high salt compared with the casein offspring (n=9-11). The gluten offspring also had fewer CD45+ leukocytes, CD11b/c+ monocytes/macrophages, CD3+ T cells, and CD45R+ B cells infiltrating the kidney. Analysis of the F2 generation gluten offspring also exhibited lower mean arterial pressure and renal damage compared with rats born from casein breeders (n=7-9), with no difference in renal immune cell infiltration. CMKLR1-receptor for the novel prohypertensive adipokine chemerin-was found via polymerase chain reaction array to be significantly upregulated (2.99-fold) in renal T cells isolated from F2 offspring of casein-fed versus gluten-fed parents. Furthermore, CMKLR1 inhibition via α-NETA (2-[α-naphthoyl] ethyltrimethylammonium iodide) treatment significantly attenuated renal immune cell infiltration, hypertension, and renal damage in SS rats fed high salt. Together, these data demonstrate the influence of the parental diet in determining the salt-induced hypertension, renal damage, and inflammatory phenotype of the offspring.
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Affiliation(s)
| | - Hayley Lund
- From the Department of Physiology, Medical College of Wisconsin, Milwaukee
| | | | | | - Ammar J Alsheikh
- From the Department of Physiology, Medical College of Wisconsin, Milwaukee
| | - David L Mattson
- From the Department of Physiology, Medical College of Wisconsin, Milwaukee
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Rodríguez‐González GL, Reyes‐Castro LA, Bautista CJ, Beltrán AA, Ibáñez CA, Vega CC, Lomas‐Soria C, Castro‐Rodríguez DC, Elías‐López AL, Nathanielsz PW, Zambrano E. Maternal obesity accelerates rat offspring metabolic ageing in a sex‐dependent manner. J Physiol 2019; 597:5549-5563. [DOI: 10.1113/jp278232] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 09/25/2019] [Indexed: 12/16/2022] Open
Affiliation(s)
| | - Luis A. Reyes‐Castro
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Claudia J. Bautista
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Azucena A. Beltrán
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Carlos A. Ibáñez
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Claudia C. Vega
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Consuelo Lomas‐Soria
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
- CONACyT‐Cátedras, Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | - Diana C. Castro‐Rodríguez
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
- CONACyT‐Cátedras, Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
| | | | - Peter W. Nathanielsz
- Wyoming Center for Pregnancy and Life Course Health ResearchDepartment of Animal ScienceUniversity Wyoming Laramie WY USA
| | - Elena Zambrano
- Reproductive BiologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico
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Chang E, Hafner H, Varghese M, Griffin C, Clemente J, Islam M, Carlson Z, Zhu A, Hak L, Abrishami S, Gregg B, Singer K. Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation. Sci Rep 2019; 9:16027. [PMID: 31690792 PMCID: PMC6831633 DOI: 10.1038/s41598-019-52583-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 10/21/2019] [Indexed: 01/07/2023] Open
Abstract
With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.
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Affiliation(s)
- E Chang
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - H Hafner
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - M Varghese
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - C Griffin
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - J Clemente
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - M Islam
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Z Carlson
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - A Zhu
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - L Hak
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - S Abrishami
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - B Gregg
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA
| | - K Singer
- Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, USA.
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50
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Maternal high-fat diet triggers metabolic syndrome disorders that are transferred to first and second offspring generations. Br J Nutr 2019; 123:59-71. [DOI: 10.1017/s0007114519002708] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractA high-fat (H) diet increases metabolic disorders in offspring. However, there is great variability in the literature regarding the time of exposure, composition of the H diets offered to the genitors and/or offspring and parameters evaluated. Here, we investigated the effect of a H diet subjected to the genitors on different cardio-metabolic parameters on first (F1)- and second (F2)-generation offspring. Female Fischer rats, during mating, gestation and breast-feeding, were subjected to the H diet (G0HF) or control (G0CF) diets. Part of F1 offspring becomes G1 genitors for generating the F2 offspring. After weaning, F1 and F2 rats consumed only the C diet. Nutritional, biometric, biochemical and haemodynamic parameters were evaluated. G0HF genitors had a reduction in food intake but energy intake was similar to the control group. Compared with the control group, the F1H and F2H offspring presented increased plasma leptin, insulin and fasting glucose levels, dietary intake, energy intake, adiposity index, mean arterial pressure, sympathetic drive evidenced by the hexamethonium and insulin resistance. Our data showed that only during mating, gestation and breast-feeding, maternal H diet induced cardio-metabolic disorders characteristic of human metabolic syndrome that were transferred to both females and males of F1 and F2 offspring, even if they were fed control diet after weaning. This process probably occurs due to the disturbance in mechanisms related to leptin that increases energy intake in F1H and F2H offspring. The present data reinforce the importance of balanced diet during pregnancy and breast-feeding for the health of the F1 and F2 offspring.
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