Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice

نویسندگان

  • Elvira Isganaitis
  • Melissa Woo
  • Huijuan Ma
  • Michael Chen
  • Wen Kong
  • Aristides Lytras
  • Vicencia Sales
  • Jennifer DeCoste-Lopez
  • Kyung-Ju Lee
  • Cianna Leatherwood
  • Deborah Lee
  • Connor Fitzpatrick
  • Walter Gall
  • Steven Watkins
  • Mary-Elizabeth Patti
چکیده

Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet

Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid su...

متن کامل

Effect of maternal variable stress on oxidative status and glucose metabolism in pubertal male rats

Introduction: Metabolic disorders are affected by negative stress experiences in the early stages of life. Accordingly, in this study, the effects of stress during pregnancy on oxidative status and glucose homeostasis in pubertal male Wistar rats were investigated. Materials and Methods: After pregnancy, female rats (200±30 g) were divided into 2 groups (6 rats per group) of stress and non-stre...

متن کامل

The Effect of Maternal High-Fat Feeding on Energy Homeostasis in Stressed Adult Male Rat Offspring

Introduction: In the present study the effect of chronic maternal high-fat diet consumption on energy homeostasis and glucose metabolism in response to chronic stress was investigated in adult male rats. Materials and Methods: Female rats were divided into two groups of normal and high fat diets. Each group received their diet from 3 weeks before pregnancy until the end of lactation. At 8 weeks...

متن کامل

Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glu...

متن کامل

Maternal serum lipid levels in pregnant women with gestational diabetes mellitus (GDM) in comparison to normal pregnant women

Background: Even though hormonal changes in pregnancy have been associated with plasma lipid variation, is not yet understood the mechanism which pregnancy alters lipid metabolism. Materials and Methods: This prospective cohort study conducted between March 2011 and May 2012 in Shariati Hospital on 112 pregnant women with GDM and 159 healthy pregnant women. In order to determine lipids or li...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 63  شماره 

صفحات  -

تاریخ انتشار 2014