title: Early overnutrition impairs insulin signaling in the heart of adult Swiss mice.
abstract: 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)-beta and IR substrate-1 (Irs1) phosphorylation, increased phosphatase, non-receptor type 1 (Ptpn1)-IR-beta 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.
authors.affiliation: Department of Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro 20550-030, Brazil.
authors.forename: Mariana Renovato
authors.initials: MR
authors.lastname: Martins
authors.forename: Anatalia Kutianski Gonzalez
authors.initials: AK
authors.lastname: Vieira
authors.forename: Erica Patrícia Garcia
authors.initials: EP
authors.lastname: de Souza
authors.forename: Anibal Sanchez
authors.initials: AS
authors.lastname: Moura
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004435:Eating; D005260:Female; D005951:Glucose Tolerance Test; D015151:Immunoblotting; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size; D044343:Overnutrition / Q000503:physiopathology*; D010766:Phosphorylation; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014280:Triglycerides; D002784:Cholesterol; D011972:Receptor, Insulin; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt