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Engin A. Misalignment of Circadian Rhythms in Diet-Induced Obesity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:27-71. [PMID: 39287848 DOI: 10.1007/978-3-031-63657-8_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronize them with daily cycles. While the central clock in the suprachiasmatic nucleus (SCN) is mainly synchronized by the light/dark cycles, the peripheral clocks react to other stimuli, including the feeding/fasting state, nutrients, sleep-wake cycles, and physical activity. During the disruption of circadian rhythms due to genetic mutations or social and occupational obligations, incorrect arrangement between the internal clock system and environmental rhythms leads to the development of obesity. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition leads to uncoupling of the peripheral clocks from the central pacemaker and to the development of metabolic disorders. The strong coupling of the SCN to the light-dark cycle creates a situation of misalignment when food is ingested during the "wrong" time of day. Food-anticipatory activity is mediated by a self-sustained circadian timing, and its principal component is a food-entrainable oscillator. Modifying the time of feeding alone greatly affects body weight, whereas ketogenic diet (KD) influences circadian biology, through the modulation of clock gene expression. Night-eating behavior is one of the causes of circadian disruption, and night eaters have compulsive and uncontrolled eating with severe obesity. By contrast, time-restricted eating (TRE) restores circadian rhythms through maintaining an appropriate daily rhythm of the eating-fasting cycle. The hypothalamus has a crucial role in the regulation of energy balance rather than food intake. While circadian locomotor output cycles kaput (CLOCK) expression levels increase with high-fat diet-induced obesity, peroxisome proliferator-activated receptor-alpha (PPARα) increases the transcriptional level of brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1) in obese subjects. In this context, effective timing of chronotherapies aiming to correct SCN-driven rhythms depends on an accurate assessment of the SCN phase. In fact, in a multi-oscillator system, local rhythmicity and its disruption reflects the disruption of either local clocks or central clocks, thus imposing rhythmicity on those local tissues, whereas misalignment of peripheral oscillators is due to exosome-based intercellular communication.Consequently, disruption of clock genes results in dyslipidemia, insulin resistance, and obesity, while light exposure during the daytime, food intake during the daytime, and sleeping during the biological night promote circadian alignment between the central and peripheral clocks. Thus, shift work is associated with an increased risk of obesity, diabetes, and cardiovascular diseases because of unusual eating times as well as unusual light exposure and disruption of the circadian rhythm.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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Dávila-Santacruz S, Corona-Quintanilla DL, Velázquez-Orozco V, Martínez-Gómez M, Castelán F, Cuevas-Romero E, Barrales-Fuentes B, Nicolás-Toledo L, Rodríguez-Antolín J. Sucrose consumption modifies the urethrogenital reflex and histological organization of the bulbospongiosus muscle in the male rat. Physiol Behav 2024; 273:114391. [PMID: 37907190 DOI: 10.1016/j.physbeh.2023.114391] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 10/06/2023] [Accepted: 10/28/2023] [Indexed: 11/02/2023]
Abstract
Disorders of the bulbospongiosus muscle (Bsm) are associated with male sexual dysfunction, such as premature ejaculation. We determined the effect of sucrose-water consumption during pregnancy-lactation and postnatal on reflex responses and morphology of Bsm fibers in adult male Wistar rat offspring. Female rats were mated and grouped into consumed tap water mothers and sucrose-water (5 %) mothers during pregnancy-lactation to obtain experimental groups. Male pups were weaned and assigned into four groups (n = 12; each group). Those from control mothers who continued drinking tap water (CM-CO group) or sucrose water (CM-SO group), and those from sucrose mothers who drank tap water (SM-CO group) or continued drinking sucrose water (SM-SO group) until adult life. In male rat offspring (n = 6 per group) was recorded the electrical activity of Bsm was recorded during penile stimulation and urethrogenital reflex (UGR). Other male rat offspring were designated for histological analysis (n = 6 per group). Sucrose consumption during prenatal stages increased the frequency of the Bsm during UGR, while pre and postnatal consumption modified muscle fiber cross-sectional area and increased the collagen content, suggesting that a combination of a diet with pre- and postnatal sucrose changes the Bsm morphophysiology possibly causing male sexual dysfunctions.
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Affiliation(s)
| | | | - Verónica Velázquez-Orozco
- Doctorado en Ciencias Biológicas, Universidad Autónoma de Tlaxcala, Mexico; Licenciatura en Química Clínica, Facultad de Ciencias de la Salud, Universidad Autónoma de Tlaxcala
| | - Margarita Martínez-Gómez
- Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, 90070 Mexico; Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Tlaxcala, Mexico
| | - Francisco Castelán
- Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, 90070 Mexico; Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Tlaxcala, Mexico
| | - Estela Cuevas-Romero
- Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, 90070 Mexico
| | | | - Leticia Nicolás-Toledo
- Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, 90070 Mexico
| | - Jorge Rodríguez-Antolín
- Centro Tlaxcala de Biología de la Conducta, Universidad Autónoma de Tlaxcala, Tlaxcala, 90070 Mexico.
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Souza LL, Rossetti CL, Peixoto TC, Manhães AC, de Moura EG, Lisboa PC. Neonatal nicotine exposure affects adult rat hepatic pathways involved in endoplasmic reticulum stress and macroautophagy in a sex-dependent manner. J Dev Orig Health Dis 2023; 14:639-647. [PMID: 38037831 DOI: 10.1017/s2040174423000326] [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] [Indexed: 12/02/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) involves changes in hepatic pathways, as lipogenesis, oxidative stress, endoplasmic reticulum (ER) stress, and macroautophagy. Maternal nicotine exposure exclusively during lactation leads to fatty liver (steatosis) only in the adult male offspring, not in females. Therefore, our hypothesis is that neonatal exposure to nicotine sex-dependently affects the signaling pathways involved in hepatic homeostasis of the offspring, explaining the hepatic lipid accumulation phenotype only in males. For this, between postnatal days 2 and 16, Wistar rat dams were implanted with osmotic minipumps, which released nicotine (NIC; 6 mg/Kg/day) or vehicle. The livers of offspring were evaluated at postnatal day 180. Only the male offspring that had been exposed to nicotine neonatally showed increased protein expression of markers of unfolded protein response (UPR), highlighting the presence of ER stress, as well as disruption of the activation of the macroautophagy repair pathway. These animals also had increased expression of diacylglycerol O-acyltransferase 1 and 4-hydroxynonenal, suggesting increased triglyceride esterification and oxidative stress. These parameters were not altered in the female offspring that had been neonatally exposed to nicotine, however they exhibited increased phospho adenosine monophosphate-activated protein kinase pAMPK expression, possibly as a protective mechanism. Thus, the disturbance in the hepatic homeostasis by UPR, macroautophagy, and oxidative stress modifications seem to be the molecular mechanisms underlying the liver steatosis in the adult male offspring of the nicotine-programming model. This highlights the importance of maternal smoking cessation during breastfeeding to decrease the risk of NAFLD development, especially in males.
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Affiliation(s)
- Luana Lopes Souza
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Camila Lüdke Rossetti
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Thamara Cherem Peixoto
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alex Christian Manhães
- Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Egberto Gaspar de Moura
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patrícia Cristina Lisboa
- Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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Cetin AK, Buyukdere Y, Gulec A, Akyol A. Taurine supplementation reduces adiposity and hepatic lipid metabolic activity in adult offspring following maternal cafeteria diet. Nutr Res 2023; 117:15-29. [PMID: 37423013 DOI: 10.1016/j.nutres.2023.06.003] [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: 01/25/2023] [Revised: 06/07/2023] [Accepted: 06/07/2023] [Indexed: 07/11/2023]
Abstract
Maternal taurine supplementation has been shown to exert protective effects following a maternal obesogenic diet on offspring growth and metabolism. However, the long-term effects of maternal cafeteria diet on adiposity, metabolic profile, and hepatic gene expression patterns following supplementation of taurine in adult offspring remains unclear. In this study, we hypothesized that exposure to maternal taurine supplementation would modulate the effects of maternal cafeteria diet by reducing adiposity and hepatic gene expression patterns involved in lipid metabolism in adult offspring. Female Wistar rats were fed a control diet, control diet supplemented with 1.5% taurine in drinking water, cafeteria diet (CAF) or CAF supplemented with taurine (CAFT) from weaning. After 8 weeks, all animals were mated and maintained on the same diets during pregnancy and lactation. After weaning, all offspring were fed with control chow diet until the age of 20 weeks. Despite similar body weights, CAFT offspring had significantly lower fat deposition and body fat when compared with CAF offspring. Microarray analysis revealed that genes (Akr1c3, Cyp7a1, Hsd17b6, Cd36, Acsm3, and Aldh1b1) related to steroid hormone biosynthesis, cholesterol metabolism, peroxisome proliferator-activated receptor signaling pathway, butanoate metabolism, and fatty acid degradation were down-regulated in CAFT offspring. The current study shows that exposure to maternal cafeteria diet promoted adiposity and taurine supplementation reduced lipid deposition and in both male and female offspring and led to alterations in hepatic gene expression patterns, reducing the detrimental effects of maternal cafeteria diet.
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Affiliation(s)
- Arzu Kabasakal Cetin
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Sihhiye, Ankara, Turkey
| | - Yucel Buyukdere
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Sihhiye, Ankara, Turkey
| | - Atila Gulec
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Sihhiye, Ankara, Turkey
| | - Asli Akyol
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
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Cohen CC, Perng W, Sauder KA, Shapiro ALB, Starling AP, Friedman C, Felix JF, Küpers LK, Moore BF, Hébert JR, Shivappa N, Scherzinger A, Sundaram SS, Shankar K, Dabelea D. Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study. J Nutr 2023; 153:1122-1132. [PMID: 36796482 PMCID: PMC10196613 DOI: 10.1016/j.tjnut.2023.01.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 01/24/2023] [Accepted: 01/31/2023] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND Overnutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. OBJECTIVES This study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4-8 y old). METHODS Data were from 278 mother-child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1-8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. RESULTS Higher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed β (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed β (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of "empty calories" were associated with higher offspring hepatic fat in early childhood. CONCLUSIONS Poorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.
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Affiliation(s)
- Catherine C Cohen
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - Wei Perng
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Katherine A Sauder
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Allison L B Shapiro
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Anne P Starling
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Chloe Friedman
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Janine F Felix
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Leanne K Küpers
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Brianna F Moore
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - James R Hébert
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Nitin Shivappa
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USA
| | - Ann Scherzinger
- Department of Radiology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Shikha S Sundaram
- Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Kartik Shankar
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes Center, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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Naomi R, Rusli RNM, Huat TS, Embong H, Bahari H, Kamaruzzaman MA. Early Intervention of Elateriospermum tapos Yoghurt in Obese Dams Mitigates Intergenerational Cognitive Deficits and Thigmotactic Behaviour in Male Offspring via the Modulation of Metabolic Profile. Nutrients 2023; 15:nu15061523. [PMID: 36986254 PMCID: PMC10052004 DOI: 10.3390/nu15061523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/19/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Maternal obesity is an intergenerational vicious cycle and one of the primary causes of cognitive deficits and high anxiety levels in offspring, which often manifest independently of sex. It is proven that curbing the intergenerational inheritance of obesity through early intervention during the gestation period has a positive outcome on the body composition, cognitive function, and anxiety level of the offspring. A recent discovery shows that the consumption of Elateriospermum tapos (E. tapos) seed extract modulates body mass and ameliorates stress hormones in obese dams, while a probiotic bacterial strain can cross the placenta and boost a child's memory. Thus, we speculate that probiotics are the best medium to integrate plant extract (E. tapos extract) to access the effect on the child's cognition. Thus, this study aimed to investigate the early intervention of E. tapos yoghurt in obese dams in the cognition and anxiety levels of male offspring. In this study, 40 female rats were fed with a high-fat diet (HFD) to induce obesity before pregnancy, while another 8 rats were fed with standard rat pellets for 16 weeks. Upon successful copulation, treatment was initiated for the obese dams up to the postnatal day (PND) 21. The groups included normal chow and saline (NS), HFD and saline (HS), HFD and yoghurt (HY), HFD and 5 mg/kg E. tapos yoghurt (HYT5), HFD and 50 mg/kg E. tapos yoghurt (HYT50), and HFD and 500 mg/kg E. tapos yoghurt (HYT500). All rats were euthanised on PND 21, and the body mass index (BMI), Lee index, and waist circumference were measured for the male offspring. Hippocampal-dependent memory tests and open field tests were conducted to access for cognition and anxiety status. Fasting blood glucose (FBG), total fat (%), insulin, leptin, lipid profile, and antioxidant parameter on serum and hypothalamus (FRAP and GSH) were accessed on PND 21. The result shows male offspring of 50 mg/kg-supplemented obese dams have comparable total fat (%), lipid profile, insulin level, FBG level, plasma insulin level, recognition index, low anxiety level, and improved hypothalamic FRAP and GSH levels to the normal group. In conclusion, this study highlights that the effect of early intervention of our novel formulation of E. tapos yoghurt in obese dams alleviates cognitive deficits and anxiety in male offspring by modulating metabolic profiles at the dose of 50 mg/kg.
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Affiliation(s)
- Ruth Naomi
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Rusydatul Nabila Mahmad Rusli
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Teoh Soo Huat
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia
| | - Hashim Embong
- Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
| | - Hasnah Bahari
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Mohd Amir Kamaruzzaman
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia
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Quek SXZ, Tan EXX, Ren YP, Muthiah M, Loo EXL, Tham EH, Siah KTH. Factors early in life associated with hepatic steatosis. World J Hepatol 2022; 14:1235-1247. [PMID: 35978672 PMCID: PMC9258263 DOI: 10.4254/wjh.v14.i6.1235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/01/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.
AIM To review the early developmental factors associated with NAFLD.
METHODS Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically.
RESULTS Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.
CONCLUSION Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.
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Affiliation(s)
- Sabrina Xin Zi Quek
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Eunice Xiang-Xuan Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Yi Ping Ren
- Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Evelyn Xiu Ling Loo
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore
| | - Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
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Stevanović-Silva J, Beleza J, Coxito P, Costa RC, Ascensão A, Magalhães J. Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise. Eur J Clin Invest 2022; 52:e13596. [PMID: 34120338 DOI: 10.1111/eci.13596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/01/2021] [Accepted: 05/06/2021] [Indexed: 12/20/2022]
Abstract
UNLABELLED SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.
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Affiliation(s)
- Jelena Stevanović-Silva
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Jorge Beleza
- Department of Cell Biology, Physiology & Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain
| | - Pedro Coxito
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Rui Carlos Costa
- Department of Communication and Art, Research Institute for Design, Media and Culture (ID+), Aveiro University, Aveiro, Portugal
| | - António Ascensão
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - José Magalhães
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
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Tajaddini A, Kendig MD, Prates KV, Westbrook RF, Morris MJ. Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females-Additive Effect of Postweaning Diet. Int J Mol Sci 2022; 23:ijms23031442. [PMID: 35163366 PMCID: PMC8835941 DOI: 10.3390/ijms23031442] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 01/07/2023] Open
Abstract
Maternal obesity increases the risk of health complications in offspring, but whether these effects are exacerbated by offspring exposure to unhealthy diets warrants further investigation. Female Sprague-Dawley rats were fed either standard chow (n = 15) or ‘cafeteria’ (Caf, n = 21) diets across pre-pregnancy, gestation, and lactation. Male and female offspring were weaned onto chow or Caf diet (2–3/sex/litter), forming four groups; behavioural and metabolic parameters were assessed. At weaning, offspring from Caf dams were smaller and lighter, but had more retroperitoneal (RP) fat, with a larger effect in males. Maternal Caf diet significantly increased relative expression of ACACA and Fasn in male and female weanling liver, but not CPT-1, SREBP and PGC1; PPARα was increased in males from Caf dams. Maternal obesity enhanced the impact of postweaning Caf exposure on adult body weight, RP fat, liver mass, and plasma leptin in males but not females. Offspring from Caf dams appeared to exhibit reduced anxiety-like behaviour on the elevated plus maze. Hepatic CPT-1 expression was reduced only in adult males from Caf fed dams. Post weaning Caf diet consumption did not alter liver gene expression in the adult offspring. Maternal obesity exacerbated the obesogenic phenotype produced by postweaning Caf diet in male, but not female offspring. Thus, the impact of maternal obesity on adiposity and liver gene expression appeared more marked in males. Our data underline the sex-specific detrimental effects of maternal obesity on offspring.
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Affiliation(s)
- Aynaz Tajaddini
- Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; (A.T.); (M.D.K.); (K.V.P.)
| | - Michael D. Kendig
- Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; (A.T.); (M.D.K.); (K.V.P.)
| | - Kelly V. Prates
- Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; (A.T.); (M.D.K.); (K.V.P.)
| | | | - Margaret J. Morris
- Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; (A.T.); (M.D.K.); (K.V.P.)
- Correspondence:
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10
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Zhou N, Du S, Dai Y, Yang F, Li X. ω3PUFAs improve hepatic steatosis in postnatal overfed rats and HepG2 cells by inhibiting acetyl-CoA carboxylase. Food Sci Nutr 2021; 9:5153-5165. [PMID: 34532024 PMCID: PMC8441356 DOI: 10.1002/fsn3.2482] [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: 03/02/2021] [Revised: 06/14/2021] [Accepted: 07/07/2021] [Indexed: 11/18/2022] Open
Abstract
Postnatal overfeeding can lead to persistent increases in hepatic lipid synthesis and the risk of nonalcoholic fatty liver disease (NAFLD) in adulthood. The ω3 polyunsaturated fatty acids (ω3PUFAs) exhibit beneficial effects on NAFLD. Here, we employed a rat model and an in vitro HepG2 cell model to investigate whether fish oil (FO) affects hepatic lipid synthesis due to postnatal overfeeding. Male Sprague-Dawley were divided into litter sizes of three (small litters, SLs) or 10 (normal litters, NLs) on postnatal day 3 and were fed standard chow or FO diet beginning on postnatal week 3 to generate NL, SL, NL-FO, and SL-FO groups. The results indicated that the FO diet reduced the postnatal overfeeding-induced body weight gain and NAFLD characteristics (such as serum and liver triglyceride (TG) and hepatic steatosis). In addition, FO restored the expression of hepatic lipid metabolism-related genes (including SCD1, FASN, CPT1, LPL, ACC, and SREBP-1c) in SL-FO rats. Specifically, the activity and expression pattern of ACC were consistent with SREBP-1c. Furthermore, HepG2 cells were treated with oleic acid (OA), followed by eicosapentenoic acid (EPA), with or without SREBP-1c siRNA. The cellular lipid droplets, TG content, and the expression of ACC (by 75%) and SREBP-1c (by 45%) were increased by OA stimulation (p < .05), which was inhibited by EPA treatment. However, the effect of EPA treatment was abolished when SREBP-1c was silenced. In conclusion, ω3PUFAs-rich diet may be an effective way to reverse the developmental programming of hepatic lipid synthesis, at least partially, by inhibiting ACC through modulating SREBP-1c.
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Affiliation(s)
- Nan Zhou
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Susu Du
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Yanyan Dai
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Fan Yang
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
| | - Xiaonan Li
- Department of Child Health CareChildren’s Hospital of Nanjing Medical UniversityNanjingChina
- Institute of Pediatric ResearchNanjing Medical UniversityNanjingChina
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11
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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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12
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Ingvorsen C, Lelliott CJ, Brix S, Hellgren LI. Effects of maternal high-fat/high sucrose diet on hepatic lipid metabolism in rat offspring. Clin Exp Pharmacol Physiol 2021; 48:86-95. [PMID: 32772427 PMCID: PMC7818417 DOI: 10.1111/1440-1681.13396] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 05/15/2020] [Accepted: 08/05/2020] [Indexed: 01/22/2023]
Abstract
Maternal obesity and/or high-fat diet during pregnancy predispose the offspring to metabolic disease. It is however unclear how pre-natal and post-natal exposure respectively affect the risk of hepatic steatosis and the trajectory towards non-alcoholic steatohepatitis in the offspring. We investigate hepatic lipid metabolism and how these factors are related to metabolic outcome in new born and young rats. Rat dams were exposed to a high-fat/high sucrose (HFHS) diet for 17 weeks prior to mating and during pregnancy. After birth, female offspring were killed and male offspring were cross-fostered, creating four groups; Control-born pups lactated by control (CC) or HFHS dams (CH) and HFHS-born pups lactated by control (HC) or HFHS dams (HH). At 4 weeks of age, pups were killed and metabolic markers in plasma were assayed, together with hepatic lipid composition and expression of relevant genes. Female HFHS neonates had smaller livers at birth (P < .05), a reduced hepatic lipid content (P < .05) and altered lipid composition. The post-natal environment dominated the metabolic profile in the male offspring at 4 weeks of age. Offspring exposed to a HFHS environment post-natally had increased adiposity (P < .0001), increased hepatic triacylglycrol accumulation (P < .0001), and an altered lipid profile with elevated n-6 polyunsaturated fatty acid (PUFA) levels (P < .0001) and a reduction in ceramide (P < .001) and monounsaturated fatty acid (MUFA) (P < .0001). In summary, maternal HFHS diet during gestation affects the hepatic lipid profile in neonates. The pre-natal exposure becomes less pronounced in young male offspring at 4 weeks of age, where the post-natal diet has the largest impact.
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Affiliation(s)
- Camilla Ingvorsen
- Department of Systems BiologyTechnical University of DenmarkKgs. LyngbyDenmark
- Centre for Fetal ProgrammingCopenhagenDenmark
- Present address:
Novo Nordisk A/SMaaloevDenmark
| | | | - Susanne Brix
- Department of Systems BiologyTechnical University of DenmarkKgs. LyngbyDenmark
- Present address:
Department of Biotechnology and BiomedicineTechnical University of DenmarkKgs. LyngbyDenmark
| | - Lars I. Hellgren
- Department of Systems BiologyTechnical University of DenmarkKgs. LyngbyDenmark
- Centre for Fetal ProgrammingCopenhagenDenmark
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13
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Keinicke H, Sun G, Mentzel CMJ, Fredholm M, John LM, Andersen B, Raun K, Kjaergaard M. FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect 2020; 9:755-768. [PMID: 32688339 PMCID: PMC7424338 DOI: 10.1530/ec-20-0152] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 07/19/2020] [Indexed: 12/11/2022]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight loss is the only available treatment, but administration of fibroblast growth factor 21 (FGF21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-induced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dosed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce inflammation and regulate hepatic leptin receptor-a expression. In conclusion, FGF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).
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Affiliation(s)
- Helle Keinicke
- Insulin and Device Trial Operations, Novo Nordisk A/S, Søborg, Denmark
| | - Gao Sun
- Pharmacology and Histopathology, Novo Nordisk A/S, China
| | - Caroline M Junker Mentzel
- Department of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Merete Fredholm
- Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Linu Mary John
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Birgitte Andersen
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Kirsten Raun
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Marina Kjaergaard
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
- Correspondence should be addressed to M Kjaergaard:
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14
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Post-weaning exposure to high-sucrose diet induces early non-alcoholic fatty liver disease onset and progression in male mice: role of dysfunctional white adipose tissue. J Dev Orig Health Dis 2020; 11:509-520. [PMID: 32594969 DOI: 10.1017/s2040174420000598] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) particularly among chronic consumers of added sugar-rich diets. However, the impact of early consumption of such diets on NAFLD onset and progression is unclear. Thus, this study sought to characterise metabolic factors involved in NAFLD progression in young mice fed with a high-sucrose diet (HSD). Male Swiss mice were fed HSD or regular chow (CTR) from weaning for up to 60 or 90 days. Obesity development, glucose homeostasis and serum biochemical parameters were determined at each time-point. At day 90, mice were euthanised and white adipose tissue (WAT) collected for lipolytic function assessment and liver for histology, gene expression and cytokines quantification. At day 60, HSD mice presented increased body mass, hypertriglyceridemia, peripheral insulin resistance (IR) and simple steatosis. Upon 90 days on diet, WAT from HSD mice displayed impaired insulin sensitivity, which coincided with increased fasting levels of glucose and free fatty acids (FFA), as well as NAFLD progression to NASH. Transcriptional levels of lipogenic genes, particularly stearoyl-CoA desaturase-1, were consistently increased, leading to hepatic leukocyte infiltration and pro-inflammatory cytokines spillover. Therefore, our dataset supports IR triggering in the WAT as a major factor for dysfunctional release of FFA towards portal circulation and consequent upregulation of lipogenic genes and hepatic inflammatory onset, which decisively concurred for NAFLD-to-NASH progression in young HSD-fed mice. Notwithstanding, this study forewarns against the early introduction of dietary sugars in infant diet, particularly following breastfeeding cessation.
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15
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Christians JK, Lennie KI, Wild LK, Garcha R. Effects of high-fat diets on fetal growth in rodents: a systematic review. Reprod Biol Endocrinol 2019; 17:39. [PMID: 30992002 PMCID: PMC6469066 DOI: 10.1186/s12958-019-0482-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 04/09/2019] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Maternal nutrition during pregnancy has life-long consequences for offspring. However, the effects of maternal overnutrition and/ or obesity on fetal growth remain poorly understood, e.g., it is not clear why birthweight is increased in some obese pregnancies but not in others. Maternal obesity is frequently studied using rodents on high-fat diets, but effects on fetal growth are inconsistent. The purpose of this review is to identify factors that contribute to reduced or increased fetal growth in rodent models of maternal overnutrition. METHODS We searched Web of Science and screened 2173 abstracts and 328 full texts for studies that fed mice or rats diets providing ~ 45% or ~ 60% calories from fat for 3 weeks or more prior to pregnancy. We identified 36 papers matching the search criteria that reported birthweight or fetal weight. RESULTS Studies that fed 45% fat diets to mice or 60% fat diets to rats generally did not show effects on fetal growth. Feeding a 45% fat diet to rats generally reduced birth and fetal weight. Feeding mice a 60% fat diet for 4-9 weeks prior to pregnancy tended to increase in fetal growth, whereas feeding this diet for a longer period tended to reduce fetal growth. CONCLUSIONS The high-fat diets used most often with rodents do not closely match Western diets and frequently reduce fetal growth, which is not a typical feature of obese human pregnancies. Adoption of standard protocols that more accurately mimic effects on fetal growth observed in obese human pregnancies will improve translational impact in this field.
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Affiliation(s)
- Julian K. Christians
- 0000 0004 1936 7494grid.61971.38Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada
| | - Kendra I. Lennie
- 0000 0004 1936 7494grid.61971.38Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada
| | - Lisa K. Wild
- 0000 0004 1936 7494grid.61971.38Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada
| | - Raajan Garcha
- 0000 0004 1936 7494grid.61971.38Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada
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16
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Kjaergaard M, Nilsson C, Nielsen MO, Grove K, Raun K. Hypothalamic oxidative stress and inflammation, and peripheral glucose homeostasis in Sprague-Dawley rat offspring exposed to maternal and postnatal chocolate and soft drink. Nutr Diabetes 2018; 8:44. [PMID: 30026488 PMCID: PMC6053394 DOI: 10.1038/s41387-018-0051-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 05/30/2018] [Accepted: 06/08/2018] [Indexed: 12/21/2022] Open
Abstract
Background Predisposition to obesity and type 2 diabetes can arise during foetal development and in early postnatal life caused by imbalances in maternal nutritional overload. We aimed to investigate the effects of maternal and postnatal intake of chocolate and soft drink on hypothalamic anti-oxidative stress markers, inflammation and peripheral glucose homeostasis. Methods Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplements (S). At birth, litter size was adjusted into 10 male offspring per dam. After weaning at 3 weeks of age, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results Offspring exposed to maternal S had up-regulated hypothalamic anti-oxidative markers such as SOD2 and catalase at 3 weeks of age as an indication of oxidative stress. However, at 12 weeks of age these anti-oxidative markers tended to decrease while pro-inflammatory markers such as TNF and IL-1β became up-regulated of all offspring exposed to S diet during some point of their life. Thus, despite an increase in anti-oxidative stress response, offspring exposed to maternal S had a reduced ability to counteract hypothalamic inflammation. At the same time point, postnatal S resulted in increased adiposity, reduced glucose tolerance and insulin sensitivity with no effect on body weight. However, at 25 weeks of age, the impaired glucose tolerance was reversible to the response of the control regardless of increased adiposity and body weight pointing towards a compensatory response of the insulin sensitivity or insulin secretion. Conclusion Indications of hypothalamic oxidative stress was observed prior to the inflammatory response in offspring exposed to maternal S. Both maternal and postnatal S induced hypothalamic inflammation prior to increased weight gain and thus contributing to obese phenotype.
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Affiliation(s)
- Marina Kjaergaard
- Diabetes and Obesity Research, Novo Nordisk A/S, Måløv, 2760, Denmark. .,Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, 1870, Denmark.
| | - Cecilia Nilsson
- Uppsala University Innovation, Uppsala Science Park, Uppsala, 751 83, Sweden
| | - Mette Olaf Nielsen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, 1870, Denmark
| | - Kevin Grove
- Diabetes and Obesity Research, Novo Nordisk A/S, Måløv, 2760, Denmark.,Division of Diabetes, Obesity and Metabolism and Division of Reproductive and Developmental Sciences, Oregon National Primate Research Centre, Oregon Health & Science University, Beaverton, OR, 97006, USA
| | - Kirsten Raun
- Diabetes and Obesity Research, Novo Nordisk A/S, Måløv, 2760, Denmark
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17
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Johnsen L, Lyckegaard NB, Khanal P, Quistorff B, Raun K, Nielsen MO. Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep. Endocr Connect 2018; 7:777-790. [PMID: 29794141 PMCID: PMC5970278 DOI: 10.1530/ec-18-0014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Accepted: 04/10/2018] [Indexed: 11/08/2022]
Abstract
OBJECTIVE We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. DESIGN Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). METHODS Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). RESULTS In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.
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Affiliation(s)
- L Johnsen
- Department of Large Animal SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - N B Lyckegaard
- Department of Large Animal SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - P Khanal
- Department of Large Animal SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - B Quistorff
- Department of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - K Raun
- Diabetes and Obesity PharmacologyNovo Nordisk A/S, Måløv, Denmark
| | - M O Nielsen
- Department of Large Animal SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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18
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Zhao M, Li Y, Yao H, Dou L, Zhang S, Zhao Q, Li L. Sex-specific Alterations in Serology and the Expression of Liver FATP4 Protein in Offspring Exposed to High-Fat Diet during Pregnancy and/or Lactation. Lipids 2018; 53:301-311. [PMID: 29701266 DOI: 10.1002/lipd.12029] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 01/20/2018] [Accepted: 01/30/2018] [Indexed: 11/06/2022]
Abstract
Changes in dietary composition will have a significant impact on the nutritional status of the mother and the offspring. To examine the relevant hormone level changes during lactation and the expression of fatty acid transporters in the placenta and liver under the condition of a high-fat (HF) diet, we established HF animal models and conducted a cross-fostering program to mimic the shift in diet. On gestation day (GD)18, the weight of placenta in the HF group was significantly higher than that in the control group (p < 0.05). HF-fed male pups had a significantly lower serum insulin level, but the same phenomenon was not found in females. On the contrary, serum triacylglycerol (TAG) level presented a tendency to decrease only in female offspring. Oil red O staining showed lipid accumulation in the HF diet offspring livers. The mRNA levels of FATP4 in the placenta in the HF diet group were significantly upregulated compared to the control diet group (p < 0.05). High-fat diet (HFD) consumption also altered the liver mRNA levels of FATP4, SREBP-1, and SCD-1 in the male offspring, while the changes in protein levels of FATP4 were not observed in either sex. In conclusion, maternal HF diet has a profound impact on offspring growth, metabolism, and the risk of metabolic disorders, which would depend on the exposure period of pregnancy and lactation.
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Affiliation(s)
- Mingqiu Zhao
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
| | - Yi Li
- Anhui Provincial Hospital, Hefei, Anhui, China
| | - Huihui Yao
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
| | - Lihua Dou
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
| | - Shuya Zhang
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
| | - Qihong Zhao
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
| | - Li Li
- Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Meishan Road, Hefei, Anhui, 230601, China
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19
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Latif R. Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review. J Matern Fetal Neonatal Med 2018. [DOI: 10.1080/14767058.2018.1449200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Rabia Latif
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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20
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Agarwal P, Morriseau TS, Kereliuk SM, Doucette CA, Wicklow BA, Dolinsky VW. Maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring. Crit Rev Clin Lab Sci 2018; 55:71-101. [DOI: 10.1080/10408363.2017.1422109] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Prasoon Agarwal
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
| | - Taylor S. Morriseau
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
| | - Stephanie M. Kereliuk
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
| | - Christine A. Doucette
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
- Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, Canada
| | - Brandy A. Wicklow
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
- Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Canada
| | - Vernon W. Dolinsky
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba, Winnipeg, Canada
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21
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Itoh H, Kanayama N. Developmental Origins of Nonalcoholic Fatty Liver Disease (NAFLD). ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1012:29-39. [PMID: 29956192 DOI: 10.1007/978-981-10-5526-3_4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence is currently increasing not only in developed obese countries but also in developing countries. Recent findings from human cohorts and animal studies suggest that a nutritional imbalance in the early critical period is causatively associated with the incidence of NAFLD in later life. Based on the current theory of the developmental origins of health and disease (DOHaD), undernourishment and overnourishment in utero are both hypothesized to prime the predisposition for hepatic fat storage. Current knowledge on the developmental origins of NAFLD is introduced in this chapter.
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Affiliation(s)
- Hiroaki Itoh
- Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
| | - Naohiro Kanayama
- Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan
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22
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Abstract
A growing epidemic of nonalcoholic fatty liver disease (NAFLD) is paralleling the increase in the incidence of obesity and diabetes mellitus in countries that consume a Western diet. As NAFLD can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma, an understanding of the factors that trigger its development and pathological progression is needed. Although by definition this disease is not associated with alcohol consumption, exposure to environmental agents that have been linked to other diseases might have a role in the development of NAFLD. Here, we focus on one class of these agents, endocrine-disrupting chemicals (EDCs), and their potential to influence the initiation and progression of a cascade of pathological conditions associated with hepatic steatosis (fatty liver). Experimental studies have revealed several potential mechanisms by which EDC exposure might contribute to disease pathogenesis, including the modulation of nuclear hormone receptor function and the alteration of the epigenome. However, many questions remain to be addressed about the causal link between acute and chronic EDC exposure and the development of NAFLD in humans. Future studies that address these questions hold promise not only for understanding the linkage between EDC exposure and liver disease but also for elucidating the molecular mechanisms that underpin NAFLD, which in turn could facilitate the development of new prevention and treatment opportunities.
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Affiliation(s)
- Charles E Foulds
- Department of Molecular and Cellular Biology, Baylor College of Medicine
- Center for Precision Environmental Health, Baylor College of Medicine
| | - Lindsey S Treviño
- Department of Molecular and Cellular Biology, Baylor College of Medicine
- Center for Precision Environmental Health, Baylor College of Medicine
| | - Brian York
- Department of Molecular and Cellular Biology, Baylor College of Medicine
- Dan L. Duncan Cancer Center, Baylor College of Medicine
| | - Cheryl L Walker
- Department of Molecular and Cellular Biology, Baylor College of Medicine
- Center for Precision Environmental Health, Baylor College of Medicine
- Dan L. Duncan Cancer Center, Baylor College of Medicine
- Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA
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23
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Meng G, Zhang B, Yu F, Li C, Zhang Q, Liu L, Wu H, Xia Y, Bao X, Shi H, Su Q, Gu Y, Fang L, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Jiao H, Wang B, Guo Q, Carvalhoa LA, Sun Z, Song K, Yu M, Niu K. Soft drinks consumption is associated with nonalcoholic fatty liver disease independent of metabolic syndrome in Chinese population. Eur J Nutr 2017; 57:2113-2121. [PMID: 28702720 DOI: 10.1007/s00394-017-1485-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 06/08/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Excessive consumption of soft drinks is associated with nonalcoholic fatty liver disease (NAFLD). However, the association between soft drinks consumption and NAFLD is unclear in non-Caucasian adults with relatively low soft drinks consumption. The aim of this study was to assess the association between soft drinks consumption and NAFLD in Chinese adults. METHODS A cross-sectional study was conducted with 26,790 adults living in Tianjin, China. NAFLD (with elevated alanine aminotransferase [ALT]) was diagnosed by the liver ultrasonography and serum ALT concentrations. Soft drinks consumption was assessed using a validated self-administered food frequency questionnaire, and it was summarized as three categories for analysis: almost never (reference), <1 cup/week, and ≥1 cups/week. Metabolic syndrome (MetS) was defined according to the criteria of the American Heart Association scientific statements of 2009. The association between soft drinks consumption and NAFLD was assessed by multiple logistic regression analysis. RESULTS The prevalence of NAFLD and NAFLD with elevated ALT was 27.1 and 6.5%, respectively. After adjustment for potential confounding variables (including MetS), the odds ratios (95% confidence intervals) for NAFLD or NAFLD with elevated ALT across soft drinks consumption were 1.00 (reference) for almost never, 1.14 (1.02-1.27) or 1.16 (0.98-1.37) for <1 cup/week, and 1.26 (1.14-1.40) or 1.32 (1.13-1.53) for ≥1 cups/week (both P for trend <0.001), respectively. CONCLUSIONS This is the first study to demonstrate that soft drinks consumption is associated with NAFLD independent of MetS in Chinese adults with relatively low soft drinks consumption. These results suggest that reducing soft drinks consumption might be beneficial to the prevention of NAFLD.
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Affiliation(s)
- Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Bo Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Fei Yu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Chunlei Li
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Yang Xia
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Xue Bao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Hongbin Shi
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qian Su
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Yeqing Gu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Liyun Fang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Huijun Yang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Bin Yu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Huanli Jiao
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China.,Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Qi Guo
- Department of Rehabilitation and Sports Medicine, Tianjin Medical University, Tianjin, China
| | - Livia A Carvalhoa
- Department of Epidemiology and Public Health, University College London, London, UK
| | - Zhong Sun
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Yu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
| | - Kaijun Niu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. .,Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China.
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24
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.
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25
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Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink. Nutr Diabetes 2017; 7:e242. [PMID: 28092346 PMCID: PMC5301042 DOI: 10.1038/nutd.2016.53] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 10/09/2016] [Accepted: 10/19/2016] [Indexed: 12/27/2022] Open
Abstract
Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Methods: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Conclusions: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.
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26
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Abstract
The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in feeding behavior and increased weight gain. Thus, shift work is associated with increased risk for obesity, diabetes and cardio-vascular diseases as a result of unusual eating time and disruption of circadian rhythm.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- , Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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27
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Affiliation(s)
- N. Tuvia
- Laboratory of Chronobiology; Institute for Medical Immunology; Charité-Universitaetsmedizin Berlin; Berlin Germany
| | - P. B. Persson
- Institute of Vegetative Physiology; Charité-Universitaetsmedizin Berlin; Berlin Germany
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28
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Pereira TJ, Moyce BL, Kereliuk SM, Dolinsky VW. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence. Biochem Cell Biol 2015; 93:438-451. [PMID: 25673017 DOI: 10.1139/bcb-2014-0141] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2023] Open
Abstract
The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, women are currently more likely than ever to enter pregnancy obese. As a result, the incidence of gestational diabetes mellitus is also on the rise. While diet and lifestyle contribute to these trends, population health data show that maternal obesity and diabetes during pregnancy during critical stages of development are major factors that contribute to the development of chronic disease in adolescent and adult offspring. Fetal programming of metabolic function, through physiological and (or) epigenetic mechanisms, may also have an intergenerational effect, and as a result may perpetuate metabolic disorders in the next generation. In this review, we summarize the existing literature that characterizes how maternal obesity and gestational diabetes mellitus contribute to metabolic and cardiovascular disorders in the offspring. In particular, we focus on animal studies that investigate the molecular mechanisms that are programmed by the gestational environment and lead to disease phenotypes in the offspring. We also review interventional studies that prevent disease with a developmental origin in the offspring.
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Affiliation(s)
- Troy J Pereira
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
| | - Brittany L Moyce
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
| | - Stephanie M Kereliuk
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
| | - Vernon W Dolinsky
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
- University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
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29
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Persson PB. Insulin. Acta Physiol (Oxf) 2015; 214:427-9. [PMID: 26100001 DOI: 10.1111/apha.12543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- P B Persson
- Institute of Vegetative Physiology, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
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30
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Affiliation(s)
- S. Reuter
- Klinik für Innere Medizin III; AG Experimentelle Nephrologie; Universitätsklinikum Jena; Jena Germany
| | - R. Mrowka
- Klinik für Innere Medizin III; AG Experimentelle Nephrologie; Universitätsklinikum Jena; Jena Germany
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31
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Pereira TJ, Fonseca MA, Campbell KE, Moyce BL, Cole LK, Hatch GM, Doucette CA, Klein J, Aliani M, Dolinsky VW. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome. J Physiol 2015; 593:3181-97. [PMID: 25922055 DOI: 10.1113/jp270429] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 04/17/2015] [Indexed: 12/16/2022] Open
Abstract
Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.
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Affiliation(s)
- Troy J Pereira
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Mario A Fonseca
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Kristyn E Campbell
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Brittany L Moyce
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Laura K Cole
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Grant M Hatch
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
| | - Christine A Doucette
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba.,Department of Physiology and Pathophysiology
| | | | - Michel Aliani
- Department of Human Nutrition, University of Manitoba, Winnipeg, MB, Canada
| | - Vernon W Dolinsky
- Department of Pharmacology & Therapeutics.,Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.,Children's Hospital Research Institute of Manitoba
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32
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Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring. Arch Toxicol 2015; 90:1211-24. [DOI: 10.1007/s00204-015-1539-0] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 05/13/2015] [Indexed: 01/28/2023]
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33
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Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life. BIOMED RESEARCH INTERNATIONAL 2015; 2015:437107. [PMID: 26090409 PMCID: PMC4450221 DOI: 10.1155/2015/437107] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 01/15/2015] [Indexed: 12/20/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.
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34
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Pruis MGM, Lendvai Á, Bloks VW, Zwier MV, Baller JFW, de Bruin A, Groen AK, Plösch T. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. Acta Physiol (Oxf) 2014; 210:215-27. [PMID: 24224789 DOI: 10.1111/apha.12197] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 10/08/2013] [Accepted: 11/10/2013] [Indexed: 02/06/2023]
Abstract
AIM Metabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. METHODS Female mice were fed either a western (W) or low-fat control (L) semisynthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. RESULTS Male offspring exposed to prenatal and post-weaning western-style diet (WW) showed hepatomegaly combined with accumulation of hepatic cholesterol and triglycerides. This accumulation was associated with up-regulation of de novo lipid synthesis, inflammation and dysregulation of lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histopathological analysis revealed the presence of advanced steatohepatitis in WW offspring. In addition, alterations in DNA methylation in key metabolic genes (Ppara, Insig, and Fasn) were detected. CONCLUSION Maternal dietary fat intake during early development programmes susceptibility to liver disease in male offspring, mediated by disturbances in lipid metabolism and inflammatory response. Long-lasting epigenetic changes may underlie this dysregulation.
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Affiliation(s)
- M. G. M. Pruis
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - Á. Lendvai
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - V. W. Bloks
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - M. V. Zwier
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - J. F. W. Baller
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - A. de Bruin
- Department of Pathobiology; Faculty of Veterinary Medicine; Utrecht University; Utrecht the Netherlands
| | - A. K. Groen
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
- Laboratory Medicine; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
| | - T. Plösch
- Department of Pediatrics; Center for Liver, Digestive and Metabolic Diseases; University of Groningen; University Medical Center Groningen; Groningen the Netherlands
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