Early overnutrition impairs insulin signaling in the heart of adult Swiss mice

Human overnutrition has caused a rise in the prevalence of obesity in recent years. In addition to the deleterious effects of obesity during childhood, long-term effects in adulthood have been described as well. For instance, cardiovascular diseases and type 2 diabetes are among the diseases associa...

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Published in:	Journal of endocrinology Vol. 198; no. 3; pp. 591 - 598
Main Authors:	Martins, Mariana Renovato, Vieira, Anatalia Kutianski Gonzalez, de Souza, Érica Patrícia Garcia, Moura, Anibal Sanchez
Format:	Journal Article
Language:	English
Published:	Bristol BioScientifica 01-09-2008
Subjects:	Animals Biological and medical sciences Blood Glucose - metabolism Body Weight Cholesterol - blood Eating Female Glucose Tolerance Test Immunoblotting Immunoprecipitation Insulin - metabolism Insulin Receptor Substrate Proteins - metabolism Intra-Abdominal Fat - metabolism Male Medical sciences Metabolic diseases Mice Obesity Organ Size Overnutrition - physiopathology Phosphorylation Pregnancy Proto-Oncogene Proteins c-akt - metabolism Receptor, Insulin - metabolism Regular papers Signal Transduction - physiology Triglycerides - blood Heart Obesity Pancreatic hormone Nutrition Rodentia Early stage Glucose Insulin Young animal Signal transduction Metabolic disorder Vertebrata Mammalia Mouse Insulin resistance High calorie diet
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Summary:	Human overnutrition has caused a rise in the prevalence of obesity in recent years. In addition to the deleterious effects of obesity during childhood, long-term effects in adulthood have been described as well. For instance, cardiovascular diseases and type 2 diabetes are among the diseases associated with a history of obesity. Altered insulin secretion and action have been described as important links between these diseases and obesity. Insulin acts as a unique anabolic hormone providing regulation of whole-body glucose homeostasis and peripheral tissue glucose uptake in tissues such as the heart. In this study, we examined insulin signaling in the heart of obese animals using an experimental model of inducing overweight adult animals by overnutrition in early life. In these animals, overfeeding during lactation was able to induce a significant increase in body weight starting at the 10th day of life, and this increased weight persisted until adulthood. Impairment in glucose tolerance, hyperinsulinemia, and an increased insulin/glucose ratio were also observed in these animals. Moreover, an increased heart weight/tibia length ratio was also observed, indicating an enlarged heart size. The overfed animals also had decreased insulin sensitivity in the heart, as confirmed by decreased insulin receptor (IR)-β and IR substrate-1 (Irs1) phosphorylation, increased phosphatase, non-receptor type 1 (Ptpn1)–IR-β association, decreased –Irs1-associated activity, and reduction in anti-phospho Akt1 phosphorylation. In conclusion, our findings showed that overnutrition during early life induced obesity and insulin resistance in the adult offspring, and further increased heart size and impaired cardiac insulin signaling, putatively due to an increase in Ptpn1 activity.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-0795 1479-6805
DOI:	10.1677/JOE-08-0057