Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams |
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| Affiliation: | 1. School of Life Sciences, Faculty of Science, University of Technology Sydney, NSW 2007, Australia;2. Department of Medicine, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW 2065, Australia;3. Inflammation and Infection Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;4. School of Medical Sciences, RMIT University, VIC, 3001, Australia;1. Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico;2. ISSSTE School of Dietetics and Nutrition, Mexico;3. Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor 62271, Mexico;1. Department of Human Anatomy, College of Medicine and Health Sciences, University of Gondar, Ethiopia;2. Paul Flechsig Institute for Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany;3. Institute of Biochemistry, University of Leipzig, Leipzig, Germany;1. Affiliated Stomatology Hospital of Xi’an Jiaotong University Health Science Center, Xi’an 710004, Shaanxi, PR China;2. College of Medicine & Forensics, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China;3. Key Laboratory of the Health Ministry for Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China;4. Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China;5. Department of Psychiatry, First Affiliated Hospital of Xi’an Jiaotong, University College of Medicine, Xi’an, Shaanxi, PR China;1. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 580, 05508-000 São Paulo, Brazil;2. Department of Neuroscience, Institute of Psychology, University of São Paulo, Av. Prof. Dr. Melo de Morais, 1721, 05508-030 São Paulo, Brazil;3. Department of Pathology, School of Veterinary Medicine, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, 05508 270 São Paulo, Brazil;4. Graduate Program of Environmental and Experimental Pathology and Graduate Program Dentistry, Paulista University, UNIP, Rua Dr. Bacelar, 1212, 04026-002 São Paulo, Brazil |
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| Abstract: | ![]()
ObjectivesMaternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of ‘transmitted disorders’ in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity.MethodsMaternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5 μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus.ResultsMaternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide-1. Ex-4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue.ConclusionShort term Ex-4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long-term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex-4 in preventing the development of metabolic disease. |
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| Keywords: | Adiposity Lipid metabolism Leptin sensitivity PGC-1α AZGP1 |
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