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Liu Y, Yu Z, Wang X, Yuan MQ, Lu MJ, Gong MR, Li Q, Xia YB, Yang GH, Xu B, Litscher G, Xu TC. Neurophysiological mechanisms of electroacupuncture in regulating pancreatic function and adipose tissue expansion. World J Diabetes 2025; 16. [DOI: doi：10.4239/wjd.v16.i5.101354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND
Electroacupuncture (EA) has been recognized for its beneficial effects on glucolipid metabolism, potentially through the regulation of sensory nerve coordination. The expandability of peripancreatic adipose tissue (PAT) is implicated in the transition from obesity to type 2 diabetes mellitus (T2DM). However, the specific pancreatic responses to EA require further elucidation.
AIM
To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet (HFD) rat model.
METHODS
To delineate the precise pathway through which EA mediates interactions between PAT and islets, we assessed the expression levels of NGF, TRPV1, insulin, as well as other proteins in the pancreas and PAT. This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.
RESULTS
The ST25, LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance (IR) to distinct degrees, with ST25 group having the greatest effect. EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system. Specifically, EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway, contributing to the relief of glucolipid metabolic stress. The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents, confirming their indispensable role in EA-mediated regulation of islet and PAT function. Furthermore, in TRPV1 knockout mice, a reduction in PAT inflammation was observed, along with the recovery of islet beta cell function. EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.
CONCLUSION
The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways. EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.
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Liu Y, Yu Z, Wang X, Yuan MQ, Lu MJ, Gong MR, Li Q, Xia YB, Yang GH, Xu B, Litscher G, Xu TC. Neurophysiological mechanisms of electroacupuncture in regulating pancreatic function and adipose tissue expansion. World J Diabetes 2025; 16:101354. [DOI: 10.4239/wjd.v16.i5.101354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/12/2025] [Accepted: 03/14/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Electroacupuncture (EA) has been recognized for its beneficial effects on glucolipid metabolism, potentially through the regulation of sensory nerve coordination. The expandability of peripancreatic adipose tissue (PAT) is implicated in the transition from obesity to type 2 diabetes mellitus (T2DM). However, the specific pancreatic responses to EA require further elucidation.
AIM To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet (HFD) rat model.
METHODS To delineate the precise pathway through which EA mediates interactions between PAT and islets, we assessed the expression levels of NGF, TRPV1, insulin, as well as other proteins in the pancreas and PAT. This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.
RESULTS The ST25, LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance (IR) to distinct degrees, with ST25 group having the greatest effect. EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system. Specifically, EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway, contributing to the relief of glucolipid metabolic stress. The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents, confirming their indispensable role in EA-mediated regulation of islet and PAT function. Furthermore, in TRPV1 knockout mice, a reduction in PAT inflammation was observed, along with the recovery of islet beta cell function. EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.
CONCLUSION The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways. EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.
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Affiliation(s)
- Yun Liu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Zhi Yu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Xuan Wang
- College of Traditional Chinese Medicine, Jiangsu Vocational College of Medicine, Yancheng 224000, Jiangsu Province, China
| | - Ming-Qian Yuan
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Meng-Jiang Lu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Mei-Rong Gong
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Qian Li
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - You-Bing Xia
- Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Guan-Hu Yang
- Department of Specialty Medicine, Ohio University, Athens, OH 45701, United States
| | - Bin Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Gerhard Litscher
- High-Tech Acupuncture and Digital Chinese Medicine, Swiss University of Traditional Chinese Medicine, Bad Zurzach 5530, Switzerland
| | - Tian-Cheng Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
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Bernecker M, Lin A, Feuchtinger A, Molenaar A, Schriever SC, Pfluger PT. Weight cycling exacerbates glucose intolerance and hepatic triglyceride storage in mice with a history of chronic high fat diet exposure. J Transl Med 2025; 23:7. [PMID: 39754229 PMCID: PMC11699648 DOI: 10.1186/s12967-024-06039-0] [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: 07/24/2024] [Accepted: 12/25/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus. METHODS Chow-fed mice and mice subjected to prolonged high-fat diet (HFD) consumption for 20 weeks, followed by 24 weeks of dietary interventions to either induce weight gain, weight loss, or weight cycling were monitored for perturbations in feeding efficiency and glucose homeostasis. Post-mortem analyses included qPCR, Western Blotting, biochemical and microscopical assessments for hepatic steatosis and insulin resistance, hypothalamic and adipose tissue inflammation, and circulating lipid, leptin and IL-6 levels. RESULTS Weight cycling led to hyperphagia and rapid weight regain, matching the weights of mice continuously on HFD. Despite weight loss, adipose tissue inflammation persisted with elevated pro-inflammatory markers, macrophage infiltration, and impaired Glut4 expression. HFD-induced dysregulation in hypothalamic expression of orexigenic peptides and synaptic plasticity markers persisted also after weight normalization suggesting long-lasting neural alterations. Weight-cycled mice exhibited higher circulating IL-6 and leptin levels, increased hepatic lipid storage, and dysregulated glucose metabolism compared to those with consistent diets, indicating worsened metabolic effects by Yoyo dieting. CONCLUSION In sum, our study highlights significant metabolic risks associated with weight cycling, particularly following prolonged obesity. Persistent adipose tissue inflammation, perturbed neural peptide and plasticity markers and impaired glucose tolerance emphasize the need for effective and sustainable weight loss strategies to mitigate the adverse outcomes of weight regain and improve long-term metabolic health.
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Affiliation(s)
- Miriam Bernecker
- Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
- Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany
- Division of NeuroBiology of Diabetes, TUM School of Medicine & Health, Technical University of Munich, Munich, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Anna Lin
- Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
- Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Annette Feuchtinger
- Core Facility Pathology and Tissue Analytics, Helmholtz Munich, Neuherberg, Germany
| | - Anna Molenaar
- Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
- Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany
- Division of NeuroBiology of Diabetes, TUM School of Medicine & Health, Technical University of Munich, Munich, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Sonja C Schriever
- Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
- Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Paul T Pfluger
- Research Unit NeuroBiology of Diabetes, Helmholtz Munich, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
- Institute for Diabetes and Obesity, Helmholtz Munich, Neuherberg, Germany.
- Division of NeuroBiology of Diabetes, TUM School of Medicine & Health, Technical University of Munich, Munich, Germany.
- German Center for Diabetes Research, Neuherberg, Germany.
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Obo T, Hashiguchi H, Matsuda E, Kawade S, Ogiso K, Iwai H, Ataka K, Yasuda O, Arimura A, Deguchi T, Morino K, Asakawa A, Nishio Y. The Anti-Obesity Effect of Fish Oil in Diet-Induced Obese Mice Occurs via Both Decreased Food Intake and the Induction of Heat Production Genes in Brown but Not White Adipose Tissue. Int J Mol Sci 2024; 26:302. [PMID: 39796158 PMCID: PMC11719521 DOI: 10.3390/ijms26010302] [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: 11/24/2024] [Revised: 12/30/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025] Open
Abstract
Omega-3 (ω-3) polyunsaturated fatty acids in fish oil have been shown to prevent diet-induced obesity in lean mice and to promote heat production in adipose tissue. However, the effects of fish oil on obese animals remain unclear. This study investigated the effects of fish oil in obese mice. C57BL/6J mice were fed a lard-based high-fat diet (LD) for 8 weeks and then assigned to either a fish oil-based high-fat diet (FOD) or continued the LD for additional 8 weeks. A control group was fed a standard diet for 16 weeks. Mice fed the FOD showed weight loss, reduced adipose tissue mass, and lower plasma insulin and leptin levels compared to those fed the LD. Rectal temperatures were higher in the FOD and LD groups compared to the control group. Energy intake was lower in the FOD group than the LD group but similar to the control group. The FOD and LD groups exhibited increased expression of heat-producing genes such as Ppargc1a, Ucp1, Adrb3, and Ppara in brown adipose tissue but not in white adipose tissue. The FOD reduced food consumption and increased rectal temperature and heat-producing genes in brown adipose tissue. Fish oil may therefore be a potential therapeutic approach to obesity.
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MESH Headings
- Animals
- Fish Oils/pharmacology
- Adipose Tissue, Brown/metabolism
- Adipose Tissue, Brown/drug effects
- Adipose Tissue, White/metabolism
- Adipose Tissue, White/drug effects
- Obesity/metabolism
- Obesity/etiology
- Obesity/drug therapy
- Obesity/genetics
- Mice
- Diet, High-Fat/adverse effects
- Male
- Mice, Inbred C57BL
- Eating/drug effects
- Anti-Obesity Agents/pharmacology
- Thermogenesis/drug effects
- Thermogenesis/genetics
- Uncoupling Protein 1/genetics
- Uncoupling Protein 1/metabolism
- Mice, Obese
- Receptors, Adrenergic, beta-3/genetics
- Receptors, Adrenergic, beta-3/metabolism
- Leptin/blood
- Insulin/blood
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
- PPAR alpha/genetics
- PPAR alpha/metabolism
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Affiliation(s)
- Takahiko Obo
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Hiroshi Hashiguchi
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Eriko Matsuda
- Department of Gene Therapy and Regenerative Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;
| | - Shigeru Kawade
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Kazuma Ogiso
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Haruki Iwai
- Department of Oral Anatomy and Cell Biology, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;
| | - Koji Ataka
- Department of Health and Nutrition, Faculty of Nursing and Nutrition, Kagoshima Immaculate Heart University, Kagoshima 895-0011, Japan;
| | - Osamu Yasuda
- Department of Sports and Life Sciences, National Institute of Fitness and Sports in Kanoya, Kanoya 891-2311, Japan;
| | - Aiko Arimura
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Takahisa Deguchi
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Katsutaro Morino
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
| | - Akihiro Asakawa
- Department of Psychosomatic Internal Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan;
| | - Yoshihiko Nishio
- Department of Diabetes and Endocrine Medicine, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (T.O.); (H.H.); (S.K.); (K.O.); (A.A.); (T.D.); (Y.N.)
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Macri EV, Touceda V, Wiszniewski M, Cacciagiú LD, Zago V, Puntarulo S, Pellegrino N, Lifshitz F, Friedman SM, Miksztowicz V. Liver response to the consumption of fried sunflower oil. J Nutr Biochem 2024; 134:109734. [PMID: 39117077 DOI: 10.1016/j.jnutbio.2024.109734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/16/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
Sunflower oil is one of the most commonly used fat sources in Argentina, and deep-fat frying is the popular food preparation process. The liver response of feeding a diet containing fried sunflower oil (SFOx) on growing rats was studied. Thirty-nine male weanling Wistar rats were randomly assigned to one of three diets for 8 wks: control (C), sunflower oil (SFO), and a diet containing SFOx, both of the sunflower diets were mixed with a commercial rat chow at weight ratio of 13% (w/w). Body weight and food consumption were recorded weekly. At t=8 wk, lipid profile and glycemia were measured. Visceral adiposity was registered. Liver was weighed and preserved for histological analysis, relative fatty acid profile, fibrosis markers and oxidative status. The three diets did not alter body weights; however, the SFOx fed rats showed increased energy intake and visceral fat; therefore, in liver saturated fat content, trans fatty acids, plus other unidentified minor components, such as hydroperoxides, hydroxides, epidioxides, hydroperoxy epidioxides, hydroxylepidioxides, and epoxides, were detected. The hepatosomatic index of SFOx rats was altered and showed hepatic steatosis. SFOx rats exhibited increased liver dichlorodihydrofluorescein-diacetate and thiobarbituric acid substance levels and oxidized-proteins content. Their livers had lower relative levels of monounsaturated, polyunsaturated fatty acids and catalase activity, but matrix metalloproteinase-9 activity was unchanged. Consumption of a diet rich in fried oil during growth could induce liver damage due to steatosis, excessive lipid toxicity and the accumulation of reactive oxygen species. Further progression could lead to hepatic fibrosis.
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Affiliation(s)
- Elisa V Macri
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina
| | - Vanessa Touceda
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina; Pontificia Universidad Católica Argentina, Facultad de Medicina, Instituto de Investigaciones Biomédicas (UCA-CONICET), Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Buenos Aires, Argentina
| | - Morena Wiszniewski
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina; Universidad de Buenos Aires, Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Buenos Aires, Argentina
| | - Leonardo D Cacciagiú
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina; Hospital General de Agudos Teodoro Álvarez. Laboratorio Central, Sección Bioquímica, Buenos Aires, Argentina
| | - Valeria Zago
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Laboratorio de Lípidos y Aterosclerosis, Hospital de Clínicas. INFIBIOC-UBA, Buenos Aires, Argentina
| | - Susana Puntarulo
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Fisicoquímica, Argentina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)- Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina
| | - Néstor Pellegrino
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bromatología, Buenos Aires, Argentina
| | - Fima Lifshitz
- Honorary Professor, State University of New York, Downstate Medical Center, College of Medicine, Brooklyn, Santa Barbara, CA, USA
| | - Silvia M Friedman
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina
| | - Verónica Miksztowicz
- Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina; Pontificia Universidad Católica Argentina, Facultad de Medicina, Instituto de Investigaciones Biomédicas (UCA-CONICET), Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Buenos Aires, Argentina.
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Nemati M, Rostamkhani F, Karbaschi R, Zardooz H. Metabolic Responses to High-Fat Feeding and Chronic Psychological Stress Combination. Endocrinol Diabetes Metab 2024; 7:e487. [PMID: 38867382 PMCID: PMC11168916 DOI: 10.1002/edm2.487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 04/07/2024] [Accepted: 04/17/2024] [Indexed: 06/14/2024] Open
Abstract
INTRODUCTION High-fat diet (HFD) consumption and being exposed to daily psychological stress, common environmental factors in modern lifestyle, play an important role on metabolic disorders such as glucose homeostasis impairment. The aim of this study was to investigate the effects of high-fat diet (HFD) and psychological stress combination on metabolic response to chronic psychological stress in male rats. METHOD Male Wistar rats were divided into HFD, and normal diet (ND) groups and then into stress and nonstress subgroups. The diets were applied for 5 weeks, and psychological stress was induced for 7 consecutive days. Then, blood samples were taken to measure glucose, insulin, free fatty acids (FFA), and leptin and corticosterone concentrations. Subsequently, glucose-stimulated insulin release from pancreatic isolated islets was assessed. RESULTS HFD did not significantly change fasting plasma glucose, insulin and corticosterone levels, whereas increased plasma leptin (7.05 ± 0.33) and FFA (p < 0.01) levels and impaired glucose tolerance. Additionally, HFD and stress combination induced more profound glucose intolerance associated with increased plasma corticosterone (p < 0.01) and leptin (8.63 ± 0.38) levels. However, insulin secretion from isolated islets did not change in the presence of high-fat diet and/or stress. CONCLUSION HFD should be considered as an intensified factor of metabolic impairments caused by chronic psychological stress.
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Affiliation(s)
- Marzieh Nemati
- Department of Physiology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
- Endocrinology and Metabolism Research CenterShiraz University of Medical ScienceShirazIran
| | - Fatemeh Rostamkhani
- Department of Biology, College of Basic Sciences, Yadegar‐e‐Imam Khomeini (RAH) BranchIslamic Azad UniversityTehranIran
| | - Roxana Karbaschi
- Faculty of Nursing and MidwiferyShahid Beheshti University of Medical SciencesTehranIran
| | - Homeira Zardooz
- Department of Physiology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
- Neurophysiology Research CenterShahid Beheshti University of Medical SciencesTehranIran
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Ritter ML, Wagner VA, Balapattabi K, Opichka MA, Lu KT, Wackman KK, Reho JJ, Keen HL, Kwitek AE, Morselli LL, Geurts AM, Sigmund CD, Grobe JL. Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice. Physiol Genomics 2024; 56:265-275. [PMID: 38145289 PMCID: PMC10866620 DOI: 10.1152/physiolgenomics.00042.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 11/15/2023] [Accepted: 12/21/2023] [Indexed: 12/26/2023] Open
Abstract
Agouti-related peptide (AgRP/Agrp) within the hypothalamic arcuate nucleus (ARC) contributes to the control of energy balance, and dysregulated Agrp may contribute to metabolic adaptation during prolonged obesity. In mice, three isoforms of Agrp are encoded via distinct first exons. Agrp-A (ENSMUST00000005849.11) contributed 95% of total Agrp in mouse ARC, whereas Agrp-B (ENSMUST00000194654.2) dominated in placenta (73%). Conditional deletion of Klf4 from Agrp-expressing cells (Klf4Agrp-KO mice) reduced Agrp mRNA and increased energy expenditure but had no effects on food intake or the relative abundance of Agrp isoforms in the ARC. Chronic high-fat diet feeding masked these effects of Klf4 deletion, highlighting the context-dependent contribution of KLF4 to Agrp control. In the GT1-7 mouse hypothalamic cell culture model, which expresses all three isoforms of Agrp (including Agrp-C, ENSMUST00000194091.6), inhibition of extracellular signal-regulated kinase (ERK) simultaneously increased KLF4 binding to the Agrp promoter and stimulated Agrp expression. In addition, siRNA-mediated knockdown of Klf4 reduced expression of Agrp. We conclude that the expression of individual isoforms of Agrp in the mouse is dependent upon cell type and that KLF4 directly promotes the transcription of Agrp via a mechanism that is superseded during obesity.NEW & NOTEWORTHY In mice, three distinct isoforms of Agouti-related peptide are encoded via distinct first exons. In the arcuate nucleus of the hypothalamus, Krüppel-like factor 4 stimulates transcription of the dominant isoform in lean mice, but this mechanism is altered during diet-induced obesity.
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Affiliation(s)
- McKenzie L Ritter
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Valerie A Wagner
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Genetics Graduate Program, University of Iowa, Iowa City, Iowa, United States
| | - Kirthikaa Balapattabi
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Megan A Opichka
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Ko-Ting Lu
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Kelsey K Wackman
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - John J Reho
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Henry L Keen
- Bioinformatics Division, Institute of Human Genetics, University of Iowa, Iowa City, Iowa, United States
| | - Anne E Kwitek
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Lisa L Morselli
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Division of Endocrinology and Molecular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Aron M Geurts
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Curt D Sigmund
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Justin L Grobe
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
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Mallick R, Basak S, Das RK, Banerjee A, Paul S, Pathak S, Duttaroy AK. Fatty Acids and their Proteins in Adipose Tissue Inflammation. Cell Biochem Biophys 2024; 82:35-51. [PMID: 37794302 PMCID: PMC10867084 DOI: 10.1007/s12013-023-01185-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/20/2023] [Indexed: 10/06/2023]
Abstract
Chronic low-grade adipose tissue inflammation is associated with metabolic disorders. Inflammation results from the intertwined cross-talks of pro-inflammatory and anti-inflammatory pathways in the immune response of adipose tissue. In addition, adipose FABP4 levels and lipid droplet proteins are involved in systemic and tissue inflammation. Dysregulated adipocytes help infiltrate immune cells derived from bone marrow responsible for producing cytokines and chemokines. When adipose tissue expands in excess, adipocyte exhibits increased secretion of adipokines and is implicated in metabolic disturbances due to the release of free fatty acids. This review presents an emerging concept in adipose tissue fat metabolism, fatty acid handling and binding proteins, and lipid droplet proteins and their involvement in inflammatory disorders.
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Affiliation(s)
- Rahul Mallick
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Sanjay Basak
- Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India
| | - Ranjit K Das
- Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Antara Banerjee
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai, India
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc, San Pablo, Queretaro, 76130, Mexico
| | - Surajit Pathak
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, Oslo, Norway.
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9
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Papadakis S, Thompson JR, Feczko E, Miranda-Dominguez O, Dunn GA, Selby M, Mitchell AJ, Sullivan EL, Fair DA. Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques. J Neurophysiol 2024; 131:241-260. [PMID: 38197176 PMCID: PMC11286309 DOI: 10.1152/jn.00213.2023] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 12/13/2023] [Accepted: 01/03/2024] [Indexed: 01/11/2024] Open
Abstract
Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet (P = 0.011) and spatial location (P = 0.003) on Iba1-stained cell count. Perinatal WSD exposure was associated with a slight decrease in the number of Iba1-stained cells, and cells were more densely located in the center of the ARC. These findings suggest that the heightened inflammatory state experienced in utero does not persist postnatally. This inflammatory response trajectory could have important implications for understanding how neurodevelopmental disorders progress.NEW & NOTEWORTHY Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.
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Affiliation(s)
- Samantha Papadakis
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States
- Department of Psychiatry, Oregon Health & Science University, Portland, Oregon, United States
| | - Jacqueline R Thompson
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States
| | - Eric Feczko
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, Minnesota, United States
| | - Oscar Miranda-Dominguez
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, Minnesota, United States
| | - Geoffrey A Dunn
- Department of Human Physiology, University of Oregon, Eugene, Oregon, United States
| | - Matthew Selby
- Department of Human Physiology, University of Oregon, Eugene, Oregon, United States
| | - A J Mitchell
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States
| | - Elinor L Sullivan
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States
- Department of Psychiatry, Oregon Health & Science University, Portland, Oregon, United States
- Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States
| | - Damien A Fair
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, Minnesota, United States
- Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, Minnesota, United States
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10
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Kwak J, Shin D. Gene-Nutrient Interactions in Obesity: COBLL1 Genetic Variants Interact with Dietary Fat Intake to Modulate the Incidence of Obesity. Int J Mol Sci 2023; 24:ijms24043758. [PMID: 36835164 PMCID: PMC9959357 DOI: 10.3390/ijms24043758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/26/2023] [Accepted: 02/02/2023] [Indexed: 02/16/2023] Open
Abstract
The COBLL1 gene is associated with leptin, a hormone important for appetite and weight maintenance. Dietary fat is a significant factor in obesity. This study aimed to determine the association between COBLL1 gene, dietary fat, and incidence of obesity. Data from the Korean Genome and Epidemiology Study were used, and 3055 Korean adults aged ≥ 40 years were included. Obesity was defined as a body mass index ≥ 25 kg/m2. Patients with obesity at baseline were excluded. The effects of the COBLL1 rs6717858 genotypes and dietary fat on incidence of obesity were evaluated using multivariable Cox proportional hazard models. During an average follow-up period of 9.2 years, 627 obesity cases were documented. In men, the hazard ratio (HR) for obesity was higher in CT, CC carriers (minor allele carriers) in the highest tertile of dietary fat intake than for men with TT carriers in the lowest tertile of dietary fat intake (Model 1: HR: 1.66, 95% confidence interval [CI]: 1.07-2.58; Model 2: HR: 1.63, 95% CI: 1.04-2.56). In women, the HR for obesity was higher in TT carriers in the highest tertile of dietary fat intake than for women with TT carriers in the lowest tertile of dietary fat intake (Model 1: HR: 1.49, 95% CI: 1.08-2.06; Model 2: HR: 1.53, 95% CI: 1.10-2.13). COBLL1 genetic variants and dietary fat intake had different sex-dependent effects in obesity. These results imply that a low-fat diet may protect against the effects of COBLL1 genetic variants on future obesity risk.
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11
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He W, Tran A, Chen CT, Loganathan N, Bazinet RP, Belsham DD. Oleate restores altered autophagic flux to rescue palmitate lipotoxicity in hypothalamic neurons. Mol Cell Endocrinol 2022; 557:111753. [PMID: 35981630 DOI: 10.1016/j.mce.2022.111753] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 07/29/2022] [Accepted: 08/10/2022] [Indexed: 01/18/2023]
Abstract
Accumulation of excess lipids in non-adipose tissues, such as the hypothalamus, is termed lipotoxicity and causative of free fatty acid-mediated pathology in metabolic disease. This study aimed to elucidate the molecular mechanisms behind oleate (OA)- and palmitate (PA)-mediated changes in hypothalamic neurons. Using the well-characterized hypothalamic neuronal cell model, mHypoE-46, we assessed gene changes through qRT-PCR, cell death with quantitative imaging, PA metabolism using stable isotope labeling, and cellular mechanisms using pharmacological modulation of lipid metabolism and autophagic flux. Palmitate (PA) disrupts gene expression, including Npy, Grp78, and Il-6 mRNA in mHypoE-46 hypothalamic neurons. Blocking PA metabolism using triacsin-C prevented the increase of these genes, implying that these changes depend on PA intracellular metabolism. Co-incubation with oleate (OA) is also potently protective and prevents cell death induced by increasing concentrations of PA. However, OA does not decrease U-13C-PA incorporation into diacylglycerol and phospholipids. Remarkably, OA can reverse PA toxicity even after significant PA metabolism and cellular impairment. OA can restore PA-mediated impairment of autophagy to prevent or reverse the accumulation of PA metabolites through lysosomal degradation, and not through other reported mechanisms. The autophagic flux inhibitor chloroquine (CQ) mimics PA toxicity by upregulating autophagy-related genes, Npy, Grp78, and Il-6, an effect partially reversed by OA. CQ also prevented the OA defense against PA toxicity, whereas the autophagy inducer rapamycin provided some protection. Thus, PA impairment of autophagic flux significantly contributes to its lipotoxicity, and OA-mediated protection requires functional autophagy. Overall, our results suggest that impairment of autophagy contributes to hypothalamic lipotoxicity.
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Affiliation(s)
- Wenyuan He
- Department of Physiology, University of Toronto, Ontario, Canada
| | - Andy Tran
- Department of Physiology, University of Toronto, Ontario, Canada
| | - Chuck T Chen
- Department of Nutritional Sciences, University of Toronto, Ontario, Canada
| | | | - Richard P Bazinet
- Department of Nutritional Sciences, University of Toronto, Ontario, Canada
| | - Denise D Belsham
- Department of Physiology, University of Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Ontario, Canada.
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12
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Meléndez-Salcido CG, Ramírez-Emiliano J, Pérez-Vázquez V. Hypercaloric Diet Promotes Metabolic Disorders and Impaired Kidney Function. Curr Pharm Des 2022; 28:3127-3139. [PMID: 36278446 DOI: 10.2174/1381612829666221020162955] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/27/2022] [Indexed: 01/28/2023]
Abstract
Poor dietary habits such as overconsumption of hypercaloric diets characterized by a high content of fructose and fat are related to metabolic abnormalities development such as obesity, diabetes, and dyslipidemia. Accumulating evidence supports the hypothesis that if energy intake gradually exceeds the body's ability to store fat in adipose tissue, the prolonged metabolic imbalance of circulating lipids from endogenous and exogenous sources leads to ectopic fat distribution in the peripheral organs, especially in the heart, liver, and kidney. The kidney is easily affected by dyslipidemia, which induces lipid accumulation and reflects an imbalance between fatty acid supply and fatty acid utilization. This derives from tissue lipotoxicity, oxidative stress, fibrosis, and inflammation, resulting in structural and functional changes that lead to glomerular and tubule-interstitial damage. Some authors indicate that a lipid-lowering pharmacological approach combined with a substantial lifestyle change should be considered to treat chronic kidney disease (CKD). Also, the new therapeutic target identification and the development of new drugs targeting metabolic pathways involved with kidney lipotoxicity could constitute an additional alternative to combat the complex mechanisms involved in impaired kidney function. In this review article, we first provide the pathophysiological evidence regarding the impact of hypercaloric diets, such as high-fat diets and high-fructose diets, on the development of metabolic disorders associated with impaired renal function and the molecular mechanisms underlying tissue lipid deposition. In addition, we present the current progress regarding translational strategies to prevent and/or treat kidney injury related to the consumption of hypercaloric diets.
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Affiliation(s)
- Cecilia Gabriela Meléndez-Salcido
- Departamento de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, 20 de enero, 929 Col. Obregón CP 37320. León, Guanajuato, México
| | - Joel Ramírez-Emiliano
- Departamento de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, 20 de enero, 929 Col. Obregón CP 37320. León, Guanajuato, México
| | - Victoriano Pérez-Vázquez
- Departamento de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, 20 de enero, 929 Col. Obregón CP 37320. León, Guanajuato, México
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13
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Safari Hasanabad M, Ghorbanlou M, Masoumi R, Shokri S, Rostami B, Mirzaei-Alamouti H, Catt S, Green MP, Nejatbakhsh R. Effects of dietary supplementation of different oils and conjugated linoleic acid on the reproductive and metabolic aspects of male mice. Andrologia 2022; 54:e14598. [PMID: 36161725 DOI: 10.1111/and.14598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 08/22/2022] [Accepted: 09/07/2022] [Indexed: 11/30/2022] Open
Abstract
The present study was carried out to examine first, if diets enriched with 320 g of the base diet with common dietary oils including fish oil, olive oil, hydrogenated sunflower seed (H-SFS) oil, flaxseed oil and sunflower seed oil (SFS) could induce weight gain and alter reproductive and metabolic characteristics of male mice. Second, whether the addition of conjugated linoleic acid (CLA, 10% of the diet) could ameliorate any negative effects. In this cross-sectional study, 90 four-week-old male NMRI mice were used in two consecutive experiments. A high level of dietary oils negatively affected some reproductive and metabolic characteristics of male mice (p < 0.05), specifically, sunflower seed oil enrichment resulted in higher HDL levels and apoptosis of germinal epithelial cells. An olive oil-enriched diet caused an increase in plasma triglyceride concentrations and germinal cell apoptosis, as well as a decrease in sperm concentration and perturbed spermatogenesis. When CLA was fed in conjunction with dietary oils it successfully mitigated some of the negative reproductive and metabolic characteristics. We conclude that male reproductive processes are affected by high dietary oils, even before signs of obesity are evident. Inclusion of dietary CLA may provide some benefit to offset negative effects, although further studies are required.
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Affiliation(s)
| | - Mehrdad Ghorbanlou
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Masoumi
- Department of Animal Science, Faculty of Agriculture, University of Zanjan, Zanjan, Iran
| | - Saeed Shokri
- School of Rural Health, Faculty of Medicine and Health, University of Sydney, Dubbo, New South Wales, Australia
| | - Behnam Rostami
- Department of Animal Science, Faculty of Agriculture, University of Zanjan, Zanjan, Iran
| | | | - Sally Catt
- Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
| | - Mark P Green
- School of BioSciences, University of Melbourne, Parkville, Melbourne, Victoria, Australia
| | - Reza Nejatbakhsh
- Department of Anatomical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
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14
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Basak S, Banerjee A, Pathak S, Duttaroy AK. Dietary Fats and the Gut Microbiota: Their impacts on lipid-induced metabolic syndrome. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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15
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Deem JD, Faber CL, Morton GJ. AgRP neurons: Regulators of feeding, energy expenditure, and behavior. FEBS J 2021; 289:2362-2381. [PMID: 34469623 DOI: 10.1111/febs.16176] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/30/2021] [Accepted: 08/31/2021] [Indexed: 12/11/2022]
Abstract
Neurons in the hypothalamic arcuate nucleus (ARC) that express agouti-related peptide (AgRP) govern a critical aspect of survival: the drive to eat. Equally important to survival is the timing at which food is consumed-seeking or eating food to alleviate hunger in the face of a more pressing threat, like the risk of predation, is clearly maladaptive. To ensure optimal prioritization of behaviors within a given environment, therefore, AgRP neurons must integrate signals of internal need states with contextual environmental cues. In this state-of-the-art review, we highlight recent advances that extend our understanding of AgRP neurons, including the neural circuits they engage to regulate feeding, energy expenditure, and behavior. We also discuss key findings that illustrate how both classical feedback and anticipatory feedforward signals regulate this neuronal population and how the integration of these signals may be disrupted in states of energy excess. Finally, we examine both technical and conceptual challenges facing the field moving forward.
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Affiliation(s)
- Jennifer D Deem
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA, USA
| | - Chelsea L Faber
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA, USA.,Department of Neurosurgery, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ, USA
| | - Gregory J Morton
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA, USA
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16
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Oliveira V, Kwitek AE, Sigmund CD, Morselli LL, Grobe JL. Recent Advances in Hypertension: Intersection of Metabolic and Blood Pressure Regulatory Circuits in the Central Nervous System. Hypertension 2021; 77:1061-1068. [PMID: 33611936 DOI: 10.1161/hypertensionaha.120.14513] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Obesity represents the single greatest ongoing roadblock to improving cardiovascular health. Prolonged obesity is associated with fundamental changes in the integrative control of energy balance, including the development of selective leptin resistance, which is thought to contribute to obesity-associated hypertension, and adaptation of resting metabolic rate (RMR) when excess weight is reduced. Leptin and the melanocortin system within the hypothalamus contribute to the control of both energy balance and blood pressure. While the development of drugs to stimulate RMR and thereby reverse obesity through activation of the melanocortin system has been pursued, most of the resulting compounds simultaneously cause hypertension. Evidence supports the concept that although feeding behaviors, RMR, and blood pressure are controlled through mechanisms that utilize similar molecular mediators, these mechanisms exist in anatomically dissociable networks. New evidence supports a major change in molecular signaling within AgRP (Agouti-related peptide) neurons of the arcuate nucleus of the hypothalamus during prolonged obesity and the existence of multiple distinct subtypes of AgRP neurons that individually contribute to control of feeding, RMR, or blood pressure. Finally, ongoing work by our laboratory and others support a unique role for AT1 (angiotensin II type 1 receptor) within one specific subtype of AgRP neuron for the control of RMR. We propose that understanding the unique biology of the AT1-expressing, RMR-controlling subtype of AgRP neurons will help to resolve the selective dysfunctions in RMR control that develop during prolonged obesity and potentially point toward novel druggable antiobesity targets that will not simultaneously cause hypertension.
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Affiliation(s)
- Vanessa Oliveira
- From the Department of Physiology (V.O., A.E.K., C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Anne E Kwitek
- From the Department of Physiology (V.O., A.E.K., C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (A.E.K., C.D.S., L.L.M., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Curt D Sigmund
- From the Department of Physiology (V.O., A.E.K., C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (A.E.K., C.D.S., L.L.M., J.L.G.), Medical College of Wisconsin, Milwaukee.,Neuroscience Research Center (C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Lisa L Morselli
- Cardiovascular Center (A.E.K., C.D.S., L.L.M., J.L.G.), Medical College of Wisconsin, Milwaukee.,Division of Endocrinology and Molecular Medicine, Department of Medicine (L.L.M.), Medical College of Wisconsin, Milwaukee
| | - Justin L Grobe
- From the Department of Physiology (V.O., A.E.K., C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (A.E.K., C.D.S., L.L.M., J.L.G.), Medical College of Wisconsin, Milwaukee.,Neuroscience Research Center (C.D.S., J.L.G.), Medical College of Wisconsin, Milwaukee.,Department of Biomedical Engineering (J.L.G.), Medical College of Wisconsin, Milwaukee.,Comprehensive Rodent Metabolic Phenotyping Core (J.L.G.), Medical College of Wisconsin, Milwaukee
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17
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Bastías-Pérez M, Serra D, Herrero L. Dietary Options for Rodents in the Study of Obesity. Nutrients 2020; 12:nu12113234. [PMID: 33105762 PMCID: PMC7690621 DOI: 10.3390/nu12113234] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/05/2020] [Accepted: 10/16/2020] [Indexed: 12/14/2022] Open
Abstract
Obesity and its associated metabolic diseases are currently a priority research area. The increase in global prevalence at different ages is having an enormous economic and health impact. Genetic and environmental factors play a crucial role in the development of obesity, and diet is one of the main factors that contributes directly to the obesogenic phenotype. Scientific evidence has shown that increased fat intake is associated with the increase in body weight that triggers obesity. Rodent animal models have been extremely useful in the study of obesity since weight gain can easily be induced with a high-fat diet. Here, we review the dietary patterns and physiological mechanisms involved in the dynamics of energy balance. We report the main dietary options for the study of obesity and the variables to consider in the use of a high-fat diet, and assess the progression of obesity and diet-induced thermogenesis.
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Affiliation(s)
- Marianela Bastías-Pérez
- Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain; (M.B.-P.); (D.S.)
| | - Dolors Serra
- Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain; (M.B.-P.); (D.S.)
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Laura Herrero
- Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain; (M.B.-P.); (D.S.)
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
- Correspondence:
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18
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Fjære E, Myrmel LS, Dybing K, Kuda O, Holbech Jensen BA, Rossmeisl M, Frøyland L, Kristiansen K, Madsen L. The Anti-Obesogenic Effect of Lean Fish Species is Influenced by the Fatty Acid Composition in Fish Fillets. Nutrients 2020; 12:E3038. [PMID: 33022997 PMCID: PMC7600456 DOI: 10.3390/nu12103038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 11/17/2022] Open
Abstract
Fillets from marine fish species contain n-3 polyunsaturated fatty acids (PUFAs) in the form of phospholipids (PLs). To investigate the importance of PL-bound n-3 PUFAs in mediating the anti-obesogenic effect of lean seafood, we compared the anti-obesogenic properties of fillets from cod with fillets from pangasius, a fresh water fish with a very low content of PL-bound n-3 PUFAs. We prepared high-fat/high-protein diets using chicken, cod and pangasius as the protein sources, and fed male C57BL/6J mice these diets for 12 weeks. Mice fed the diet containing cod gained less adipose tissue mass and had smaller white adipocytes than mice fed the chicken-containing diet, whereas mice fed the pangasius-containing diet were in between mice fed the chicken-containing diet and mice fed the cod-containing diet. Of note, mice fed the pangasius-containing diet exhibited reduced glucose tolerance compared to mice fed the cod-containing diet. Although the sum of marine n-3 PUFAs comprised less than 2% of the total fatty acids in the cod-containing diet, this was sufficient to significantly increase the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in mouse tissues and enhance production of n-3 PUFA-derived lipid mediators as compared with mice fed pangasius or chicken.
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Affiliation(s)
- Even Fjære
- Institute of Marine Research, NO-5817 Bergen, Norway; (E.F.); (L.S.M.); (K.D.); (L.F.)
| | - Lene Secher Myrmel
- Institute of Marine Research, NO-5817 Bergen, Norway; (E.F.); (L.S.M.); (K.D.); (L.F.)
| | - Karianne Dybing
- Institute of Marine Research, NO-5817 Bergen, Norway; (E.F.); (L.S.M.); (K.D.); (L.F.)
| | - Ondrej Kuda
- Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, 14220 Prague 4, Czech Republic; (O.K.); (M.R.)
| | - Benjamin Anderschou Holbech Jensen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark;
| | - Martin Rossmeisl
- Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, 14220 Prague 4, Czech Republic; (O.K.); (M.R.)
| | - Livar Frøyland
- Institute of Marine Research, NO-5817 Bergen, Norway; (E.F.); (L.S.M.); (K.D.); (L.F.)
| | - Karsten Kristiansen
- Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark;
| | - Lise Madsen
- Institute of Marine Research, NO-5817 Bergen, Norway; (E.F.); (L.S.M.); (K.D.); (L.F.)
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19
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Valent D, Arroyo L, Fàbrega E, Font-i-Furnols M, Rodríguez-Palmero M, Moreno-Muñoz J, Tibau J, Bassols A. Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model. Benef Microbes 2020; 11:347-359. [DOI: 10.3920/bm2019.0197] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The pig is a valuable animal model to study obesity in humans due to the physiological similarity between humans and pigs in terms of digestive and associated metabolic processes. The dietary use of vegetal protein, probiotics and omega-3 fatty acids is recommended to control weight gain and to fight obesity-associated metabolic disorders. Likewise, there are recent reports on their beneficial effects on brain functions. The hypothalamus is the central part of the brain that regulates food intake by means of the production of food intake-regulatory hypothalamic neuropeptides, as neuropeptide Y (NPY), orexin A and pro-opiomelanocortin (POMC), and neurotransmitters, such as dopamine and serotonin. Other mesolimbic areas, such as the hippocampus, are also involved in the control of food intake. In this study, the effect of a high fat diet (HFD) alone or supplemented with these additives on brain neuropeptides and neurotransmitters was assessed in forty-three young pigs fed for 10 weeks with a control diet (T1), a high fat diet (HFD, T2), and HFD with vegetal protein supplemented with Bifidobacterium breve CECT8242 alone (T3) or in combination with omega-3 fatty acids (T4). A HFD provoked changes in regulatory neuropeptides and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and alterations mostly in the dopaminergic system in the ventral hippocampus. Supplementation of the HFD with B. breve CECT8242, especially in combination with omega-3 fatty acids, was able to partially reverse the effects of HFD. Correlations between productive and neurochemical parameters supported these findings. These results confirm that pigs are an appropriate animal model alternative to rodents for the study of the effects of HFD on weight gain and obesity. Furthermore, they indicate the potential benefits of probiotics and omega-3 fatty acids on brain function.
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Affiliation(s)
- D. Valent
- Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària. Universitat Autònoma de Barcelona, Barcelona, Spain
| | - L. Arroyo
- Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària. Universitat Autònoma de Barcelona, Barcelona, Spain
| | - E. Fàbrega
- Food Science – Institut de Recerca i Tecnologia Agroalimentàries, IRTA, Monells, Girona, Spain
| | - M. Font-i-Furnols
- Animal Science – Institut de Recerca i Tecnologia Agroalimentàries, IRTA, Monells, Girona, Spain
| | | | | | - J. Tibau
- Animal Science – Institut de Recerca i Tecnologia Agroalimentàries, IRTA, Monells, Girona, Spain
| | - A. Bassols
- Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària. Universitat Autònoma de Barcelona, Barcelona, Spain
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20
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Deng G, Morselli LL, Wagner VA, Balapattabi K, Sapouckey SA, Knudtson KL, Rahmouni K, Cui H, Sigmund CD, Kwitek AE, Grobe JL. Single-Nucleus RNA Sequencing of the Hypothalamic Arcuate Nucleus of C57BL/6J Mice After Prolonged Diet-Induced Obesity. Hypertension 2020; 76:589-597. [PMID: 32507042 DOI: 10.1161/hypertensionaha.120.15137] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Prolonged obesity is associated with blunted feeding and thermogenic autonomic responses to leptin, but cardiovascular responses to leptin are maintained. This state of selective leptin resistance is, therefore, proposed to contribute to the pathogenesis and maintenance of obesity-associated hypertension. Cells of the arcuate nucleus of the hypothalamus detect leptin, and although the cellular and molecular mechanisms remain unclear, altered arcuate nucleus biology is hypothesized to contribute to selective leptin resistance. Male C57BL/6J mice were fed a high-fat diet (HFD) or chow from 8 to 18 weeks of age, as this paradigm models selective leptin resistance. Nuclei were then isolated from arcuate nucleus for single-nucleus RNA sequencing. HFD caused expected gains in adiposity and circulating leptin. Twenty-three unique cell-type clusters were identified, and Ingenuity Pathway Analysis was used to explore changes in gene expression patterns due to chronic HFD within each cluster. Notably, gene expression signatures related to leptin signaling exhibited suppression predominantly in neurons identified as the Agouti-related peptide (Agrp) subtype. Ingenuity Pathway Analysis results were also consistent with alterations in CREB (cAMP response element-binding protein) signaling in Agrp neurons after HFD, and reduced phosphorylated CREB was confirmed in arcuate nucleus after prolonged HFD by capillary electrophoresis-based Western blotting. These findings support the concept that prolonged HFD-induced obesity is associated with selective changes in Agrp neuron biology, possibly secondary to altered CREB signaling.
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Affiliation(s)
- Guorui Deng
- From the Department of Neuroscience and Pharmacology (G.D., S.A.S., K.R., H.C.), University of Iowa
| | - Lisa L Morselli
- Division of Endocrinology, Department of Internal Medicine (L.L.M.), University of Iowa
| | - Valerie A Wagner
- Department of Physiology (V.A.W., K.B., C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Kirthikaa Balapattabi
- Department of Physiology (V.A.W., K.B., C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Sarah A Sapouckey
- From the Department of Neuroscience and Pharmacology (G.D., S.A.S., K.R., H.C.), University of Iowa
| | | | - Kamal Rahmouni
- From the Department of Neuroscience and Pharmacology (G.D., S.A.S., K.R., H.C.), University of Iowa.,Obesity Research and Education Initiative (K.R., H.C.), University of Iowa.,Iowa Neuroscience Institute (K.R., H.C.), University of Iowa
| | - Huxing Cui
- From the Department of Neuroscience and Pharmacology (G.D., S.A.S., K.R., H.C.), University of Iowa.,Obesity Research and Education Initiative (K.R., H.C.), University of Iowa.,Iowa Neuroscience Institute (K.R., H.C.), University of Iowa
| | - Curt D Sigmund
- Department of Physiology (V.A.W., K.B., C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee
| | - Anne E Kwitek
- Department of Physiology (V.A.W., K.B., C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee.,Department of Medicine (A.E.K.), Medical College of Wisconsin, Milwaukee
| | - Justin L Grobe
- Department of Physiology (V.A.W., K.B., C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee.,Cardiovascular Center (C.D.S., A.E.K., J.L.G.), Medical College of Wisconsin, Milwaukee.,Department of Biomedical Engineering (J.L.G.), Medical College of Wisconsin, Milwaukee.,Comprehensive Rodent Metabolic Phenotyping Core (J.L.G.), Medical College of Wisconsin, Milwaukee
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21
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Khatun MA, Sato S, Konishi T. Obesity preventive function of novel edible mushroom, Basidiomycetes-X (Echigoshirayukidake): Manipulations of insulin resistance and lipid metabolism. J Tradit Complement Med 2020; 10:245-251. [PMID: 32670819 PMCID: PMC7340980 DOI: 10.1016/j.jtcme.2020.03.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 03/09/2020] [Accepted: 03/18/2020] [Indexed: 01/04/2023] Open
Abstract
Echigoshirayukidake is an edible mushroom found in Uonuma, Japan in 1994. It was assigned to a new species of Basidiomycetes (BDM-X) but is uniquely defect of forming bashidium. The high antioxidant activity and β-glucan content of BDM-X suggest possible functions preventing type 2 diabetes. In the present study, anti-obesity and insulin resistance preventive functions of BDM-X were examined using genetically defined obese model rat, OLETF (Otsuka Long Evans Tokushima Fatty) by feeding regular diet with and without supplementation of 5% dried BDM-X powder (BDMP) for 15 weeks. BDMP supplementation to the diet significantly (p < 0.01) suppressed the body weight gain and also visceral fat accumulation during the feeding period compared to control diet. Simultaneously, the insulin resistance and the plasma levels of adiponectin and triglycerides were significantly (p = 0.003) ameliorated in the BDMP supplemented diet group. A statistical multivariate analysis showed the weight of three types of adipose tissue (epididymal, retroperirenal, and mesenteric fat) positively correlated with HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), and negatively correlated with plasma adiponectin. These results indicate BDM-X is a new resource applicable to the functional foods or the complementary biomedicines to prevent metabolic syndromes leading to type 2 diabetes.
A new mushroom, Echigoshirayukidake (BDM-X), ameliorates postprandial sugar and insulin spike enhancing insulin sensitivity. BDM-X prevented body weight gain, hyperlipidemia, NEFA, and visceral fat deposition. HOMA-IR was improved by BDM-X. Anti-metabolic syndrome effect of BDM-X could be related to increase of adiponectin level.
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Affiliation(s)
- Mst Afifa Khatun
- Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, 956-8603, Japan.,Food Safety and Quality Analysis Division, Institute of Food and Radiation Biology, Atomic Energy Research Establishment, Savar, Dhaka, 1000, Bangladesh
| | - Shinji Sato
- Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, 956-8603, Japan
| | - Tetsuya Konishi
- Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, 956-8603, Japan.,Office HALD Food Function Research, Yuzawa, Minami-Uonuma City, Niigata, 949-6103, Japan
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22
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Calvano A, Izuora K, Oh EC, Ebersole JL, Lyons TJ, Basu A. Dietary berries, insulin resistance and type 2 diabetes: an overview of human feeding trials. Food Funct 2020; 10:6227-6243. [PMID: 31591634 DOI: 10.1039/c9fo01426h] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Dietary berries are a rich source of several nutrients and phytochemicals and in recent years, accumulating evidence suggests they can reduce risks of several chronic diseases, including type 2 diabetes (T2D). The objective of this review is to summarize and discuss the role of dietary berries (taken as fresh, frozen, or other processed forms) on insulin resistance and biomarkers of T2D in human feeding studies. Reported feeding trials involve different berries taken in different forms, and consequently differences in nutritional or polyphenol composition must be considered in their interpretation. Commonly consumed berries, especially cranberries, blueberries, raspberries and strawberries, ameliorate postprandial hyperglycemia and hyperinsulinemia in overweight or obese adults with insulin resistance, and in adults with the metabolic syndrome (MetS). In non-acute long-term studies, these berries either alone, or in combination with other functional foods or dietary interventions, can improve glycemic and lipid profiles, blood pressure and surrogate markers of atherosclerosis. Studies specifically in people with T2D are few, and more knowledge is needed. Nevertheless, existing evidence, although sparse, suggests that berries have an emerging role in dietary strategies for the prevention of diabetes and its complications in adults. Despite the beneficial effects of berries on diabetes prevention and management, they must be consumed as part of a healthy and balanced diet.
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Affiliation(s)
- Aaron Calvano
- Department of Kinesiology and Nutrition Sciences, University of Nevada at Las Vegas, Las Vegas, Nevada, USA.
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23
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Zhao L, Wang Y, Zhang G, Zhang T, Lou J, Liu J. L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet. Nutrients 2019; 11:nu11123054. [PMID: 31847305 PMCID: PMC6950088 DOI: 10.3390/nu11123054] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 12/07/2019] [Accepted: 12/10/2019] [Indexed: 12/26/2022] Open
Abstract
Obesity and metabolic syndrome (MS) associated with excess calorie intake has become a great public health concern worldwide. L-arabinose, a naturally occurring plant pentose, has a promising future as a novel food ingredient with benefits in MS; yet the mechanisms remain to be further elucidated. Gut microbiota is recently recognized to play key roles in MS. Molecular hydrogen, an emerging medical gas with reported benefits in MS, can be produced and utilized by gut microbes. Here we show oral L-arabinose elicited immediate and robust release of hydrogen in mice in a dose-and-time-dependent manner while alleviating high-fat-diet (HFD) induced MS including increased body weight especially fat weight, impaired insulin sensitivity, liver steatosis, dyslipidemia and elevated inflammatory cytokines. Moreover, L-arabinose modulated gene-expressions involved in lipid metabolism and mitochondrial function in key metabolic tissues. Antibiotics treatment abolished L-arabinose-elicited hydrogen production independent of diet type, confirming gut microbes as the source of hydrogen. q-PCR of fecal 16S rDNA revealed modulation of relative abundances of hydrogen-producing and hydrogen-consuming gut microbes as well as probiotics by HFD and L-arabinose. Our data uncovered modulating gut microbiota and hydrogen yield, expression of genes governing lipid metabolism and mitochondrial function in metabolic tissues is underlying L-arabinose's benefits in MS.
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24
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Saande CJ, Webb JL, Curry PE, Rowling MJ, Schalinske KL. Dietary Whole Egg Reduces Body Weight Gain in a Dose-Dependent Manner in Zucker Diabetic Fatty Rats. J Nutr 2019; 149:1766-1775. [PMID: 31254347 DOI: 10.1093/jn/nxz143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/22/2019] [Accepted: 06/04/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND We previously reported that a whole-egg-based diet attenuated weight gain in rats with type 2 diabetes (T2D) and more effectively maintained vitamin D status than an equivalent amount of supplemental cholecalciferol. OBJECTIVES The objective of this study was to determine the lowest dose of whole egg effective at maintaining vitamin D homeostasis and attenuating the obese phenotype in T2D rats. METHODS Zucker diabetic fatty (ZDF) rats (n = 40; age 6 wk; prediabetic) and their lean controls (n = 40; age 6 wk) were randomly assigned to a diet containing 20% casein (CAS) or 20%, 10%, 5%, or 2.5% protein from whole egg (20% EGG, 10% EGG, 5% EGG, and 2.5% EGG, respectively). All diets contained 20% total protein (wt:wt). All rats received their respective diets for 8 wk, at a stage of growth and development that translates to adolescence in humans, until 14 wk of age, a point at which ZDF rats exhibit overt T2D. Weight gain was measured 5 d/wk, and circulating 25-hydroxyvitamin D [25(OH)D] was measured by ELISA. Mean values were compared by 2-factor ANOVA. RESULTS The 20% EGG diet maintained serum 25(OH)D at 30 nmol/L in ZDF rats, whereas the 10%, 5%, and 2.5% EGG diets did not prevent insufficiency, resulting in mean serum 25(OH)D concentrations of 24 nmol/L in ZDF rats. Body weight gain was reduced by 29% (P < 0.001) and 31% (P < 0.001) in ZDF rats consuming 20% and 10% EGG diets, respectively, and by 16% (P = 0.004) and 12% (P = 0.030) in ZDF rats consuming 5% and 2.5% EGG diets, respectively, compared with CAS. CONCLUSIONS Whole-egg-based diets exerted a dose-dependent response with respect to attenuating weight gain. These data could support dietary recommendations aimed at body weight management in individuals predisposed to obesity and T2D.
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Affiliation(s)
- Cassondra J Saande
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.,Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA
| | - Joseph L Webb
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.,Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA
| | - Paige E Curry
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA
| | - Matthew J Rowling
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.,Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA
| | - Kevin L Schalinske
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.,Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA
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25
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Sawczyn T, Stygar D, Nabrdalik K, Kukla M, Skrzep-Poloczek B, Wesołowski B, Olszańska E, Dulska A, Gumprecht J, Karcz WK, Jochem J. The influence of high fat diet on plasma incretins and insulin concentrations in Sprague-Dawley rats with diet-induced obesity and glucose intolerance undergoing ileal transposition. Peptides 2019; 115:75-84. [PMID: 30954533 DOI: 10.1016/j.peptides.2019.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 03/19/2019] [Accepted: 04/01/2019] [Indexed: 02/01/2023]
Abstract
BACKGROUND The benefits of IT surgery are based on incretin effects. In this study we show the influence of high fat diet (HFD) used both before and after surgery, on ileal transposition (IT) effects. METHODS Forty-eight male rats were assigned to two groups: HFD and control diet (CD) fed rats. After eight weeks, HFD and CD fed rats were randomly assigned to two types of surgery: IT and SHAM, then for 50% of animals of each group the diet was changed, whereas the other 50% received the same type of diet. Eight weeks after surgery the incretin level, glucose tolerance as well as body mass and insulin level were assessed. RESULTS GLP-1 plasma concentration was significantly higher in the IT operated CD/CD group compared to fasting state and did not differ significantly from the SHAM operated CD/CD animals. IT influenced the glucose stimulated PYY plasma level when compared with SHAM operated animals in the CD/HFD group, where the PYY plasma level was higher than in the SHAM operated animals. The effect of IT as well as of pre and postoperative diet on GIP plasma levels were insignificant. The IT group members maintained on the CD were characterised by a lower fasting glucose level, both pre and postoperatively, compared with the SHAM operated animals. The effect of IT on the fasting glucose level in groups preoperatively maintained on an HFD was insignificant. CONCLUSIONS IT surgery itself seems to have rather limited incretin effects in rats, whose obesity is the result of HFD.
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Affiliation(s)
- Tomasz Sawczyn
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Dominika Stygar
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Nabrdalik
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Michał Kukla
- Department of Gastroenterology and Hepatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Bronisława Skrzep-Poloczek
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Bartosz Wesołowski
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Ewa Olszańska
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Dulska
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Wojciech Konrad Karcz
- Department of General, Visceral, Transplantation and Vascular Surgery, Hospital of the Ludwig Maximilian University, Munich, Germany
| | - Jerzy Jochem
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
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26
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Fish oil supplementation during adolescence attenuates metabolic programming of perinatal maternal high-fat diet in adult offspring. Br J Nutr 2019; 121:1345-1356. [PMID: 30940241 DOI: 10.1017/s0007114519000771] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.
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27
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Carranza Martin AC, Coleman DN, Garcia LG, Furnus CC, Relling AE. Prepartum fatty acid supplementation in sheep. III. Effect of eicosapentaenoic acid and docosahexaenoic acid during finishing on performance, hypothalamus gene expression, and muscle fatty acids composition in lambs. J Anim Sci 2019; 96:5300-5310. [PMID: 30239813 DOI: 10.1093/jas/sky360] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 09/05/2018] [Indexed: 12/25/2022] Open
Abstract
The objectives of this study were to evaluate the effect of feeding an enriched diet with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to finishing lambs born from ewes supplemented either with or without EPA and DHA during late gestation on productive performance, muscle fatty acid (FA), and hypothalamus mRNA concentration of metabolic genes and hormone receptors. Lambs born from dams fed during the last 50 d of gestation either with a control diet containing 0.39% Ca salts of palmitic fatty acid distillate (C) or Ca salts enriched with EPA and DHA (PFA) were used. After weaning lambs (n = 70) were blocked by weight (BW) and used in a 2 × 2 factorial into 2 finishing diets containing 1.5% of C or PFA. The 2 factors were the ewe diet and the finishing diet. Lambs (37.9 ± 0.4 kg) were weighed and blood sampled for glucose and NEFA measurements at days 1, 14, 28, and 42. Dry matter intake (DMI) was measured daily. At day 43, 14 females and 14 males were slaughtered, and hot carcass weight, body wall thickness, rib eye area, and FA composition of Longissumus thoracis muscle were evaluated. Female hypothalamuses were obtained and mRNA concentration of hormone receptors, neuropeptides, and their receptors was measured. Lambs born from PFA dams were heavier (P < 0.01). There was a time × finishing diet interaction for BW (P = 0.03), and lambs fed C had a greater BW. Lambs fed C had an increase in DMI (P < 0.01). There were no significant differences in plasma glucose and NEFA concentration (P > 0.1). Lambs born from PFA dams had a greater concentration of C22:0 (P < 0.03). Lambs fed C had higher concentrations of C18:1c15 (P < 0.01), C17:0 (P < 0.09), C18:0 (P < 0.09), and n6/n3 (P < 0.01). Lambs fed PFA had greater concentration (P < 0.05) of C16:1, C22:1, C20:5, C22:5, C22:6, total n3 FA, and total EPA and DHA. There was a significant dam × finishing diet interaction (P ≤ 0.08) on mRNA concentration for MCR3, CCK-R, Cort-R, and CART. Lambs, which had the same treatment as their dams, showed lower overall mRNA concentration than those with different treatments between them and their dams. Lambs born from PFA ewes had lower concentration of MCR4 mRNA (P = 0.09) than C. Agouti-related peptides mRNA concentration was lower in lambs fed PFA (P = 0.06) than C. In conclusion, changes on lamb performance, muscle fatty acid composition, and metabolic neuropeptides depend not only on the lamb diet, but also on the dam diet during late gestation.
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Affiliation(s)
- Ana Cristina Carranza Martin
- IGEVET - Instituto de Genética Veterinaria Prof. Fernando N. Dulout (UNLP-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (1900), La Plata, Buenos Aires, Argentina.,Department of Animal Sciences, Ohio State University, Wooster, OH
| | | | | | - Cecilia C Furnus
- IGEVET - Instituto de Genética Veterinaria Prof. Fernando N. Dulout (UNLP-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata (1900), La Plata, Buenos Aires, Argentina
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28
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Miao YF, Kang HX, Li J, Zhang YM, Ren HY, Zhu L, Chen H, Yuan L, Su H, Wan MH, Tang WF. Effect of Sheng-jiang powder on multiple-organ inflammatory injury in acute pancreatitis in rats fed a high-fat diet. World J Gastroenterol 2019; 25:683-695. [PMID: 30783372 PMCID: PMC6378539 DOI: 10.3748/wjg.v25.i6.683] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/10/2019] [Accepted: 01/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obesity worsens inflammatory organ injury in acute pancreatitis (AP), but there is no effective preventive strategy. Sheng-jiang powder (SJP) has been shown to alleviate multiple-organ inflammatory injury in rats with high-fat diet-induced obesity. Hence, SJP is supposed to have an effect on multiple-organ inflammatory injury in AP in rats fed a high-fat diet.
AIM To explore how obesity may contribute to aggravating inflammatory organ injury in AP in rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet.
METHODS Rats were randomly assigned to a control group (CG), an obese group (OG), and an SJP treatment group (SG), with eight rats per group. The rats in the OG and SG were fed a high-fat diet. From the third week, the rats in the SG were given oral doses of SJP (5 g/kg of body weight). After 12 wk, AP was induced in the three groups. Serum amylase level, body weight, Lee’s index, serum biochemistry parameters, and serum inflammatory cytokine and tissue cytokine levels were assessed, and the tissue histopathological scores were evaluated and compared.
RESULTS Compared with the CG, serum triglyceride, total cholesterol, interleukin-6, and interleukin-10 levels were significantly higher in the OG, and serum high-density lipoprotein cholesterol level was significantly lower in the OG. Moreover, enhanced oxidative damage was observed in the pancreas, heart, spleen, lung, intestine, liver, and kidney. Evidence of an imbalanced antioxidant defense system, especially in the pancreas, spleen, and intestine, was observed in the obese AP rats. Compared with the OG, serum high-density lipoprotein cholesterol, interleukin-10, and superoxide dismutase expression levels in the pancreas, spleen, and intestine were increased in the SG. Additionally, SJP intervention led to a decrease in the following parameters: body weight; Lee’s index; serum triglyceride levels; serum total cholesterol levels; malondialdehyde expression levels in the pancreas, heart, spleen, lung, and liver; myeloperoxidase expression levels in the lung; and pathological scores in the liver.
CONCLUSION Obesity may aggravate the inflammatory reaction and pathological multiple-organ injury in AP rats, and SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.
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Affiliation(s)
- Yi-Fan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Xin Kang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Juan Li
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Mei Zhang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Yu Ren
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hang Su
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Abstract
We provide an overview of studies on seafood intake in relation to obesity, insulin resistance and type 2 diabetes. Overweight and obesity development is for most individuals the result of years of positive energy balance. Evidence from intervention trials and animal studies suggests that frequent intake of lean seafood, as compared with intake of terrestrial meats, reduces energy intake by 4–9 %, sufficient to prevent a positive energy balance and obesity. At equal energy intake, lean seafood reduces fasting and postprandial risk markers of insulin resistance, and improves insulin sensitivity in insulin-resistant adults. Energy restriction combined with intake of lean and fatty seafood seems to increase weight loss. Marine n-3 PUFA are probably of importance through n-3 PUFA-derived lipid mediators such as endocannabinoids and oxylipins, but other constituents of seafood such as the fish protein per se, trace elements or vitamins also seem to play a largely neglected role. A high intake of fatty seafood increases circulating levels of the insulin-sensitising hormone adiponectin. As compared with a high meat intake, high intake of seafood has been reported to reduce plasma levels of the hepatic acute-phase protein C-reactive protein level in some, but not all studies. More studies are needed to confirm the dietary effects on energy intake, obesity and insulin resistance. Future studies should be designed to elucidate the potential contribution of trace elements, vitamins and undesirables present in seafood, and we argue that stratification into responders and non-responders in randomised controlled trials may improve the understanding of health effects from intake of seafood.
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Fernández-Gayol O, Sanchis P, Aguilar K, Navarro-Sempere A, Comes G, Molinero A, Giralt M, Hidalgo J. Different Responses to a High-Fat Diet in IL-6 Conditional Knockout Mice Driven by Constitutive GFAP-Cre and Synapsin 1-Cre Expression. Neuroendocrinology 2019; 109:113-130. [PMID: 30636247 DOI: 10.1159/000496845] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 01/12/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, at least in part through actions in the central nervous system (CNS) from local sources. METHODS We herewith report results obtained in conditional IL-6 KO mice for brain cells (Il6ΔGfap and Il6ΔSyn). RESULTS The reporter RiboTag mouse line demonstrated specific astrocytic expression of GFAP-dependent Cre in the hypothalamus but not in other brain areas, whereas that of synapsin 1-dependent Cre was specific for neurons. Feeding a high-fat diet (HFD) or a control diet showed that Il6ΔGfap and Il6ΔSyn mice were more prone and resistant, respectively, to HFD-induced obesity. Energy intake was not altered in HFD experiments, but it was reduced in Il6ΔSyn male mice following a 24-h fast. HFD increased circulating insulin, leptin, and cholesterol levels, decreased triglycerides, and caused impaired responses to the insulin and glucose tolerance tests. In Il6ΔGfap mice, the only significant difference observed was an increase in insulin levels of females, whereas in Il6ΔSyn mice the effects of HFD were decreased. Hypothalamic Agrp expression was significantly decreased by HFD, further decreased in Il6ΔGfap, and increased in Il6ΔSyn female mice. Hypothalamic Il-6 mRNA levels were not decreased in Il6ΔSyn mice and even increased in Il6ΔGfapmale mice. Microarray analysis of hypothalamic RNA showed that female Il6ΔGfap mice had increased interferon-related pathways and affected processes in behavior, modulation of chemical synaptic transmission, learning, and memory. CONCLUSION The present results demonstrate that brain production of IL-6 regulates body weight in the context of caloric excess and that the cellular source is critical.
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Affiliation(s)
- Olaya Fernández-Gayol
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Paula Sanchis
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Kevin Aguilar
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Alicia Navarro-Sempere
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Gemma Comes
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Amalia Molinero
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mercedes Giralt
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Juan Hidalgo
- Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain,
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Pham VM, Matsumura S, Katano T, Funatsu N, Ito S. Diabetic neuropathy research: from mouse models to targets for treatment. Neural Regen Res 2019; 14:1870-1879. [PMID: 31290436 PMCID: PMC6676867 DOI: 10.4103/1673-5374.259603] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.
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Affiliation(s)
- Vuong M Pham
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan; Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore
| | - Shinji Matsumura
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Tayo Katano
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Nobuo Funatsu
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Seiji Ito
- Department of Medical Chemistry, Kansai Medical University, Hirakata; Department of Anesthesiology, Osaka Medical College, Takatsuki, Osaka, Japan
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32
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Yu Y, Patch C, Weston-Green K, Zhou Y, Zheng K, Huang XF. Dietary Galacto-Oligosaccharides and Resistant Starch Protect Against Altered CB1 and 5-HT1A and 2A Receptor Densities in Rat Brain: Implications for Preventing Cognitive and Appetite Dysfunction During a High-Fat Diet. Mol Nutr Food Res 2018; 62:e1800422. [PMID: 30152105 DOI: 10.1002/mnfr.201800422] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 07/26/2018] [Indexed: 11/07/2022]
Abstract
SCOPE A high-fat, but low-fiber, diet is associated with obesity and cognitive dysfunction, while dietary fiber supplementation can improve cognition. METHODS AND RESULTS This study examines whether dietary fibers, galacto-oligosaccharides (GOS) and resistant starch (RS), could prevent high-fat (HF)-diet-induced alterations in neurotransmitter receptor densities in brain regions associated with cognition and appetite. Rats are fed a HF diet, HF diet with GOS, HF diet with RS, or a low-fat (LF, control) diet for 4 weeks. Cannabinoid CB1 (CB1R) and 5HT1A (5HT1A R) and 5-HT2A (5HT2A R) receptor binding densities are examined. In the hippocampus and hypothalamus, a HF diet significantly increases CB1R binding, while HF + GOS and HF + RS diets prevented this increase. HF diet also increases hippocampal and hypothalamic 5-HT1A R binding, while HF + GOS and HF + RS prevented the alterations. Increased 5-HT2A binding is prevented by HF + GOS and HF + RS in the medial mammillary nucleus. CONCLUSIONS These results demonstrate that increased CB1R, 5-HT1A R and 5-HT2A R induced by a HF diet can be prevented by GOS and RS supplementation in brain regions involved in cognition and appetite. Therefore, increased fiber intake may have beneficial effects on improving learning and memory, as well as reducing excessive appetite, during the chronic consumption of a HF (standard Western) diet.
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Affiliation(s)
- Yinghua Yu
- Illawarra Health and Medical Research Institute and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, NSW, 2522, Australia
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Jiangsu, 221004, China
| | - Craig Patch
- Illawarra Health and Medical Research Institute and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, NSW, 2522, Australia
| | - Katrina Weston-Green
- Illawarra Health and Medical Research Institute and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, NSW, 2522, Australia
| | - Yuan Zhou
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Jiangsu, 221004, China
| | - Kuiyang Zheng
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Jiangsu, 221004, China
| | - Xu-Feng Huang
- Illawarra Health and Medical Research Institute and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, NSW, 2522, Australia
- Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Jiangsu, 221004, China
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33
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Canter RJ, Le CT, Beerthuijzen JM, Murphy WJ. Obesity as an immune-modifying factor in cancer immunotherapy. J Leukoc Biol 2018; 104:487-497. [PMID: 29762866 PMCID: PMC6113103 DOI: 10.1002/jlb.5ri1017-401rr] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 04/17/2018] [Accepted: 04/18/2018] [Indexed: 12/18/2022] Open
Abstract
Immunotherapy has achieved breakthrough status in many advanced stage malignancies and is rapidly becoming the fourth arm of cancer treatment. Although cancer immunotherapy has generated significant excitement because of the potential for complete and sometimes durable responses, there is also the potential for severe and occasionally life-threatening toxicities, including cytokine release syndrome and severe autoimmunity. A large body of work also points to a "metainflammatory" state in obesity associated with impairment of immune responses. Because immune checkpoint blockade (and other cancer immunotherapies) have altered the landscape of immunotherapy in cancer, it is important to understand how immune responses are shaped by obesity and how obesity may modify both immunotherapy responses and potential toxicities.
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Affiliation(s)
- Robert J. Canter
- University of California, Davis, School of Medicine, Department of Surgery, Division of Surgical Oncology, Sacramento, CA 95817
| | - Catherine T Le
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
| | - Johanna M.T. Beerthuijzen
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
| | - William J. Murphy
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
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Tse EK, Salehi A, Clemenzi MN, Belsham DD. Role of the saturated fatty acid palmitate in the interconnected hypothalamic control of energy homeostasis and biological rhythms. Am J Physiol Endocrinol Metab 2018; 315:E133-E140. [PMID: 29631363 DOI: 10.1152/ajpendo.00433.2017] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The brain, specifically the hypothalamus, controls whole body energy and glucose homeostasis through neurons that synthesize specific neuropeptides, whereas hypothalamic dysfunction is linked directly to insulin resistance, obesity, and type 2 diabetes mellitus. Nutrient excess, through overconsumption of a Western or high-fat diet, exposes the hypothalamus to high levels of free fatty acids, which induces neuroinflammation, endoplasmic reticulum stress, and dysregulation of neuropeptide synthesis. Furthermore, exposure to a high-fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders. While whole brain/animal studies have provided phenotypic end points and important clues to the genes involved, there are still major gaps in our understanding of the intracellular pathways and neuron-specific components that ultimately control circadian rhythms and energy homeostasis. Because of its complexity and heterogeneous nature, containing a diverse mix cell types, it is difficult to dissect the critical hypothalamic components involved in these processes. Of significance, we have the capacity to study these individual components using an extensive collection of both embryonic- and adult-derived, immortalized hypothalamic neuronal cell lines from rodents. These defined neuronal cell lines have been used to examine the impact of nutrient excess, such as palmitate, on circadian rhythms and neuroendocrine signaling pathways, as well as changes in vital neuropeptides, leading to the development of neuronal inflammation; the role of proinflammatory molecules in this process; and ultimately, restoration of normal signaling, clock gene expression, and neuropeptide synthesis in disrupted states by beneficial anti-inflammatory compounds in defined hypothalamic neurons.
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Affiliation(s)
- Erika K Tse
- Department of Physiology, University of Toronto , Toronto, Ontario , Canada
| | - Ashkan Salehi
- Department of Physiology, University of Toronto , Toronto, Ontario , Canada
| | - Matthew N Clemenzi
- Department of Physiology, University of Toronto , Toronto, Ontario , Canada
| | - Denise D Belsham
- Department of Physiology, University of Toronto , Toronto, Ontario , Canada
- Department Obstetrics and Gynaecology and Medicine, University of Toronto , Toronto, Ontario , Canada
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35
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Hu T, Yang Z, Li MD. Pharmacological Effects and Regulatory Mechanisms of Tobacco Smoking Effects on Food Intake and Weight Control. J Neuroimmune Pharmacol 2018; 13:453-466. [PMID: 30054897 DOI: 10.1007/s11481-018-9800-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/16/2018] [Indexed: 12/26/2022]
Abstract
Beyond promoting smoking initiation and preventing smokers from quitting, nicotine can reduce food intake and body weight and thus is viewed as desirable by some smokers, especially many women. During the last several decades, the molecular mechanisms underlying the inverse correlation between smoking and body weight have been investigated extensively in both animals and humans. Nicotine's weight effects appear to result especially from the drug's stimulation of α3β4 nicotine acetylcholine receptors (nAChRs), which are located on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC), leading to activation of the melanocortin circuit, which is associated with body weight. Further, α7- and α4β2-containing nAChRs have been implicated in weight control by nicotine. This review summarizes current understanding of the regulatory effects of nicotine on food intake and body weight according to the findings from pharmacological, molecular genetic, electrophysiological, and feeding studies on these appetite-regulating molecules, such as α3β4, α7, and α4β2 nAChRs; neuropeptide Y (NPY); POMC; melanocortin 4 receptor (MC4R); agouti-related peptide (AgRP); leptin, ghrelin, and protein YY (PYY).
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Affiliation(s)
- Tongyuan Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhongli Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.
| | - Ming D Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China. .,Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China. .,Institute of Neuroimmune Pharmacology, Seton Hall University, South Orange, NJ, USA.
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36
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37
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Calarco CA, Lee S, Picciotto MR. Access to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice. Neuropharmacology 2017; 123:210-220. [PMID: 28623168 PMCID: PMC5544033 DOI: 10.1016/j.neuropharm.2017.06.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 06/08/2017] [Accepted: 06/12/2017] [Indexed: 11/25/2022]
Abstract
Nicotine and tobacco use is associated with lower body weight, and many smokers report concerns about weight. In animal studies, nicotine reduces weight gain, reduces food consumption, and alters energy expenditure, but these effects vary with duration and route of nicotine administration. Previous studies have used standardized nicotine doses, however, in this study, male and female mice had free access to nicotine drinking water for 30 days while fed either a high fat diet (HFD) or chow, allowing animals to titrate their nicotine intake. In male mice, HFD increased body weight and caloric intake. Nicotine attenuated this effect and decreased weight gain per calorie consumed without affecting overall caloric intake or acute locomotion, suggesting metabolic changes. Nicotine did not decrease weight in chow-fed animals. In contrast, the same paradigm did not result in significant differences in weight gain in female animals, but did alter corticosterone levels and locomotion, indicating sex differences in the response to HFD and nicotine. We measured levels of mRNAs encoding nicotinic acetylcholine receptor subunits, uncoupling proteins (UCP) 1-3, and neuropeptides involved in energy balance in adipose tissues and the arcuate nucleus of the hypothalamus (ARC). HFD and nicotine regulated UCP levels in adipose tissues and ARC from female, but not male, mice. Regulation of agouti-related peptide, neuropeptide-Y, melanin-concentrating hormone, and cocaine- and amphetamine-regulated transcript in ARC varied with diet and nicotine in a sex-dependent manner. These data demonstrate that chronic consumption of nicotine moderates the effect of HFD in male mice by changing metabolism rather than food intake, and identify a differential effect on female mice.
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Affiliation(s)
- Cali A Calarco
- Department of Psychiatry and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06508, United States
| | - Somin Lee
- Department of Psychiatry and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06508, United States
| | - Marina R Picciotto
- Department of Psychiatry and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06508, United States.
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Koo BK. Letter: Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density? (Diabetes Metab J 2017;41:121-7). Diabetes Metab J 2017; 41:223-224. [PMID: 28657236 PMCID: PMC5489503 DOI: 10.4093/dmj.2017.41.3.223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Bo Kyung Koo
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
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39
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Jang M, Park SY, Kim YW, Jung SP, Kim JY. Response: Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density? (Diabetes Metab J 2017;41:121-7). Diabetes Metab J 2017; 41:225-227. [PMID: 28657237 PMCID: PMC5489504 DOI: 10.4093/dmj.2017.41.3.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Affiliation(s)
- Mi Jang
- Obesity-Diabetes Advanced Research Center, Yeungnam University College of Medicine, Daegu, Korea
| | - So Young Park
- Obesity-Diabetes Advanced Research Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Yong Woon Kim
- Obesity-Diabetes Advanced Research Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Seung Pil Jung
- Obesity-Diabetes Advanced Research Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Jong Yeon Kim
- Obesity-Diabetes Advanced Research Center, Yeungnam University College of Medicine, Daegu, Korea.
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40
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Liver ERα regulates AgRP neuronal activity in the arcuate nucleus of female mice. Sci Rep 2017; 7:1194. [PMID: 28446774 PMCID: PMC5430776 DOI: 10.1038/s41598-017-01393-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 03/27/2017] [Indexed: 01/22/2023] Open
Abstract
Recent work revealed the major role played by liver Estrogen Receptor α (ERα) in the regulation of metabolic and reproductive functions. By using mutant mice with liver-specific ablation of Erα, we here demonstrate that the hepatic ERα is essential for the modulation of the activity of Agouti Related Protein (AgRP) neurons in relation to the reproductive cycle and diet. Our results suggest that the alterations of hepatic lipid metabolism due to the lack of liver ERα activity are responsible for a neuroinflammatory status that induces refractoriness of AgRP neurons to reproductive and dietary stimuli. The study therefore points to the liver ERα as a necessary sensor for the coordination of systemic energy metabolism and reproductive functions.
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41
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Barbosa MMDAL, Damasceno NRT. The benefits of ω-3 supplementation depend on adiponectin basal level and adiponectin increase after the supplementation: A randomized clinical trial. Nutrition 2017; 34:7-13. [DOI: 10.1016/j.nut.2016.08.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/11/2016] [Accepted: 08/23/2016] [Indexed: 01/28/2023]
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Mericq V, Martinez-Aguayo A, Uauy R, Iñiguez G, Van der Steen M, Hokken-Koelega A. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol 2017; 13:50-62. [PMID: 27539244 DOI: 10.1038/nrendo.2016.127] [Citation(s) in RCA: 166] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Accumulating evidence suggests that both the intrauterine environment and growth during early life can influence the development of chronic noncommunicable diseases, such as type 2 diabetes mellitus and cardiovascular disease, in adulthood. Here, we review the available human data supporting increased metabolic risk among children born premature or small for gestational age; the adrenal and pubertal modifications that contribute to this risk; metabolic changes that occur during adolescence and early adulthood; and approaches to potentially modify or decrease risk of metabolic disease. The risks associated with delivery at term or preterm are compared for each period of life. Knowledge of these associations is fundamental for the paediatric community to develop preventive strategies early during postnatal life.
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Affiliation(s)
- Veronica Mericq
- Institute of Maternal and Child Research, University of Chile, Santiago, 8330091, Chile
| | - Alejandro Martinez-Aguayo
- Pediatrics Division, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8330074, Chile
| | - Ricardo Uauy
- Pediatrics Division, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, 8330074, Chile
- Institute of Nutrition and Food Technology, University of Chile, Santiago, 7810851, Chile
| | - German Iñiguez
- Institute of Maternal and Child Research, University of Chile, Santiago, 8330091, Chile
| | - Manouk Van der Steen
- Dutch Growth Research Foundation, 3001 KB Rotterdam, The Netherlands
- Department of Pediatrics, Subdivision of Endocrinology, Erasmus University Medical Center, Sophia Children's Hospital, 3000 CB Rotterdam, The Netherlands
| | - Anita Hokken-Koelega
- Dutch Growth Research Foundation, 3001 KB Rotterdam, The Netherlands
- Department of Pediatrics, Subdivision of Endocrinology, Erasmus University Medical Center, Sophia Children's Hospital, 3000 CB Rotterdam, The Netherlands
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Reynolds CM, Segovia SA, Vickers MH. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring. Front Endocrinol (Lausanne) 2017; 8:245. [PMID: 28993758 PMCID: PMC5622157 DOI: 10.3389/fendo.2017.00245] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 09/06/2017] [Indexed: 12/17/2022] Open
Abstract
Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.
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Affiliation(s)
| | | | - Mark H. Vickers
- Liggins Institute, University of Auckland, Auckland, New Zealand
- *Correspondence: Mark H. Vickers,
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Singh P, Kesharwani RK, Keservani RK. Protein, Carbohydrates, and Fats. SUSTAINED ENERGY FOR ENHANCED HUMAN FUNCTIONS AND ACTIVITY 2017:103-115. [DOI: 10.1016/b978-0-12-805413-0.00006-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Velasco C, Bonacic K, Soengas JL, Morais S. Orally administered fatty acids enhance anorectic potential but do not activate central fatty acid sensing in Senegalese sole post-larvae. ACTA ACUST UNITED AC 2016; 220:677-685. [PMID: 27927695 DOI: 10.1242/jeb.150979] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/30/2016] [Indexed: 12/12/2022]
Abstract
Studies in fish have reported the presence and function of fatty acid (FA)-sensing systems comparable in many aspects to those known in mammals. Such studies were carried out in juvenile and adult fish, but the presence of FA-sensing systems and control of food intake have never been evaluated in early life stages, despite the importance of establishing when appetite regulation becomes functional in larval fish. In this study, we aimed to elucidate the possible effects of different specific FAs on neural FA-sensing systems and neuropeptides involved in the control of food intake in Senegalese sole post-larvae. To achieve this, we orally administered post-larvae with different solutions containing pure FA - oleate (OA), linoleate (LA), α-linolenate (ALA) or eicosapentaenoate (EPA) - and evaluated changes in mRNA abundance of neuropeptides involved in the control of food intake and of transcripts related to putative FA-sensing systems, 3 and 6 h post-administration. The changes in neuropeptide gene expression were relatively consistent with the activation of anorectic pathways (enhanced cart4 and pomcb) and a decrease in orexigenic factors (npy) following intake of FA. Even though there were a few differences depending on the nature of the FA, the observed changes appear to suggest the existence of a putative anorectic response in post-larvae fish to the ingestion of all four tested FAs. However, changes in neuropeptides cannot be explained by the integration of metabolic information regarding FAs in circulation through FA-sensing mechanisms in the brain. Only the reduction in mRNA levels of the FA metabolism gene acc in OA-treated (6 h), ALA-treated (3 h) and EPA-treated (3 and 6 h) post-larvae could be indicative of the presence of a FA-sensing system, but most genes either were not significantly regulated (fat/cd36-lmp2, acly, kir6.x, srebp1c) or were affected in a way that was inconsistent with FA-sensing mechanisms (fat/cd36-pg4l, fas, cpt1.1, cpt1.2, cpt1.3, sur, pparα and lxrα).
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Affiliation(s)
- Cristina Velasco
- Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo E-36310, Spain
| | - Kruno Bonacic
- IRTA, Ctra. Poble Nou Km 5.5, Sant Carles de la Ràpita 43540, Spain
| | - José L Soengas
- Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo E-36310, Spain
| | - Sofia Morais
- IRTA, Ctra. Poble Nou Km 5.5, Sant Carles de la Ràpita 43540, Spain .,Lucta S.A., Innovation Division, UAB Research Park, Eureka building, Bellaterra 08193, Spain
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Wang XJ, Xu SH, Liu L, Song ZG, Jiao HC, Lin H. Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens. ACTA ACUST UNITED AC 2016; 220:607-614. [PMID: 27903700 DOI: 10.1242/jeb.143792] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 11/23/2016] [Indexed: 01/08/2023]
Abstract
Dietary fat affects appetite and appetite-related peptides in birds and mammals; however, the effect of dietary fat on appetite is still unclear in chickens faced with different energy statuses. Two experiments were conducted to investigate the effects of dietary fat on food intake and hypothalamic neuropeptides in chickens subjected to two feeding states or two diets. In Experiment 1, chickens were fed a high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. In Experiment 2, chickens that were fed a HF or LF diet for 35 days were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF (HF-RLF, LF-RLF) diet for 3 h. The results showed that chickens fed a HF diet for 35 days had increased body fat deposition despite decreasing food intake even when the diet was altered during the re-feeding period (P<0.05). LF diet (35 days) promoted agouti-related peptide (AgRP) expression compared with HF diet (P<0.05) under both fed and fasted conditions. LF-RHF chickens had lower neuropeptide Y (NPY) expression compared with LF-RLF chickens; conversely, HF-RHF chickens had higher NPY expression than HF-RLF chickens (P<0.05). These results demonstrate: (1) that HF diet decreases food intake even when the subsequent diet is altered; (2) the orexigenic effect of hypothalamic AgRP; and (3) that dietary fat alters the response of hypothalamic NPY to subsequent energy intake. These findings provide a novel view of the metabolic perturbations associated with long-term dietary fat over-ingestion in chickens.
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Affiliation(s)
- Xiao J Wang
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
| | - Shao H Xu
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
| | - Lei Liu
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
| | - Zhi G Song
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
| | - Hong C Jiao
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
| | - Hai Lin
- Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong 271018, China
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Ehrampoush E, Homayounfar R, Davoodi SH, Zand H, Askari A, Kouhpayeh SA. Ability of dairy fat in inducing metabolic syndrome in rats. SPRINGERPLUS 2016; 5:2020. [PMID: 27994997 PMCID: PMC5125350 DOI: 10.1186/s40064-016-3716-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Accepted: 11/21/2016] [Indexed: 12/11/2022]
Abstract
Background The risk of heart diseases, diabetes and stroke is increased with higher metabolic risk factors. Models of diseases resulting from high-calorie diets have a significant role in pathophysiologic analysis of metabolic syndrome in rodents; but, these diets are considerably different from each other in various studies and may not be very similar to the metabolic syndrome model in humans. This study sought to make a model close to the disease in humans. 20 five-week old male Wistar rats were randomly assigned to two groups. For one of the groups, a high-calorie diet with 416 calories per 100 g with dairy-based fat was considered and, for another group, a control diet was given for 12 weeks. Weight changes, lipid profile, glucose values, Blood pressure, insulin and HOMA indices, were measured for both groups and weight changes were compared using repeated measures and independent t test; also, serum results were compared using independent t test. Results Values of weight, glucose, insulin, lipid profile and blood pressure, except HDL, had a tangible difference between two groups at the end of the study. HOMA-IR, HOMA-B and HOMA-S indicates a significant difference between the two groups after consumption high-energy diet. Conclusion The present study showed ability of dairy fat in gaining weight, insulin resistance and metabolic syndrome and provided the necessity of paying serious attention to the amount of fat intake from dairy sources.
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Affiliation(s)
- Elham Ehrampoush
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.,Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Homayounfar
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.,Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sayed Hossein Davoodi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Zand
- National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Askari
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Seyed Amin Kouhpayeh
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
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Metabolic dysfunction following weight cycling in male mice. Int J Obes (Lond) 2016; 41:402-411. [PMID: 27840414 PMCID: PMC5344184 DOI: 10.1038/ijo.2016.193] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 08/30/2016] [Accepted: 09/23/2016] [Indexed: 12/15/2022]
Abstract
Background Combatting over-weight or obesity can lead to large fluctuations in an individual’s body weight, often referred to as weight cycling or “yo-yo” dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting. Methods Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF respectively) or switched to a high fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups) while FC and FF groups were placed on a high fat diet (FCF and FFF) (n=28/group). Results For the majority of metabolic outcomes changes aligned with dietary switches; however assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared to animals maintained on a high fat diet (Internal Fat: FCF: 7.4 ± 0.2g vs. FFF: 5.6 ± 0.2g; p<0.01). Conclusions Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. While further work will be required to elucidate the mechanisms underlying the neuronal control of energy homeostasis, these studies provide a causative link between weight cycling and adverse health.
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Mamounis KJ, Yasrebi A, Roepke TA. Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse. J Nutr Biochem 2016; 40:122-131. [PMID: 27886622 DOI: 10.1016/j.jnutbio.2016.10.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 10/27/2016] [Accepted: 10/27/2016] [Indexed: 01/22/2023]
Abstract
A significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.
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Affiliation(s)
- Kyle J Mamounis
- Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
| | - Ali Yasrebi
- Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
| | - Troy A Roepke
- Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; New Jersey Institute for Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
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50
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Dalvi PS, Chalmers JA, Luo V, Han DY, Wellhauser L, Liu Y, Tran DQ, Castel J, Luquet S, Wheeler MB, Belsham DD. High fat induces acute and chronic inflammation in the hypothalamus: effect of high-fat diet, palmitate and TNF-α on appetite-regulating NPY neurons. Int J Obes (Lond) 2016; 41:149-158. [PMID: 27773938 DOI: 10.1038/ijo.2016.183] [Citation(s) in RCA: 163] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 08/18/2016] [Accepted: 09/18/2016] [Indexed: 12/25/2022]
Abstract
BACKGROUND Consumption of dietary fat is one of the key factors leading to obesity. High-fat diet (HFD)-induced obesity is characterized by induction of inflammation in the hypothalamus; however, the temporal regulation of proinflammatory markers and their impact on hypothalamic appetite-regulating neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons remains undefined. METHODS Mice were injected with an acute lipid infusion for 24 h or fed a HFD over 8-20 weeks. Characterized mouse NPY/AgRP hypothalamic cell lines were used for in vitro experimentation. Immunohistochemistry in brain slices or quantitative real-time PCR in cell lines, was performed to determine changes in the expression of key inflammatory markers and neuropeptides. RESULTS Hypothalamic inflammation, indicated by tumor necrosis factor (TNF)-α expression and astrocytosis in the arcuate nucleus, was evident following acute lipid infusion. HFD for 8 weeks suppressed TNF-α, while significantly increasing heat-shock protein 70 and ciliary neurotrophic factor, both neuroprotective components. HFD for 20 weeks induced TNF-α expression in NPY/AgRP neurons, suggesting a detrimental temporal regulatory mechanism. Using NPY/AgRP hypothalamic cell lines, we found that palmitate provoked a mixed inflammatory response on a panel of inflammatory and endoplasmic reticulum (ER) stress genes, whereas TNF-α significantly upregulated IκBα, nuclear factor (NF)-κB and interleukin-6 mRNA levels. Palmitate and TNF-α exposure predominantly induced NPY mRNA levels. Utilizing an I kappa B kinase β (IKKβ) inhibitor, we demonstrated that these effects potentially occur via the inflammatory IKKβ/NF-κB pathway. CONCLUSIONS These findings indicate that acute lipid and chronic HFD feeding in vivo, as well as acute palmitate and TNF-α exposure in vitro, induce markers of inflammation or ER stress in the hypothalamic appetite-stimulating NPY/AgRP neurons over time, which may contribute to a dramatic alteration in NPY/AgRP content or expression. Acute and chronic HFD feeding in vivo temporally regulates arcuate TNF-α expression with reactive astrocytosis, which suggests a time-dependent neurotrophic or neurotoxic role of lipids.
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Affiliation(s)
- P S Dalvi
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - J A Chalmers
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - V Luo
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - D-Yd Han
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - L Wellhauser
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Y Liu
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - D Q Tran
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - J Castel
- Unité de Biologie Fonctionnelle et Adaptative, University of Paris Diderot, Sorbonne Paris Cité, CNRS UMR 8251, Paris, France
| | - S Luquet
- Unité de Biologie Fonctionnelle et Adaptative, University of Paris Diderot, Sorbonne Paris Cité, CNRS UMR 8251, Paris, France
| | - M B Wheeler
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - D D Belsham
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
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