Maternal high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice

Abstract

Intrauterine environment may influence the health of postnatal offspring. There have been many studies on the effects of maternal high-fat diet (HFD) on diabetes and glucose metabolism in offspring. Here, we investigated the effects in male and female offspring. C57/BL6J mice were bred and fed either control diet (CD) or HFD from conception to weaning, and offspring were fed CD or HFD from 6 to 20 wk. At 20 wk, maternal HFD induced glucose intolerance and insulin resistance in offspring. Additionally, liver triacylglycerol content, adipose tissue mass, and inflammation increased in maternal HFD. In contrast, extending previous observations, insulin secretion at glucose tolerance test, islet area, insulin content, and PDX-1 mRNA levels in isolated islets were lower in maternal HFD in males, whereas they were higher in females. Oxidative stress in islets increased in maternal HFD in males, whereas there were no differences in females. Plasma estradiol levels were lower in males than in females and decreased in offspring fed HFD and also decreased by maternal HFD, suggesting that females may be protected from insulin deficiency by inhibiting oxidative stress. In conclusion, maternal HFD induced insulin resistance and deterioration of pancreatic ␤-cell function, with marked sex differences in adult offspring accompanied by adipose tissue inflammation and liver steatosis. Additionally, our results demonstrate that potential mechanisms underlying sex differences in pancreatic ␤-cell function may be related partially to increases in oxidative stress in male islets and decreased plasma estradiol levels in males.

Dietary inflammation potential and postmenopausal breast cancer risk in a German case-control study

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Decreased basal insulin secretion from pancreatic islets of pups in a rat model of maternal obesity

“…In utero exposure to excess maternal lipids could affect a number of pathways in developing organs, such as the liver, skeletal muscle, adipose tissue, brain and pancreas (Bringhenti et al 2013). Maternal high-fat diet during pregnancy and lactation induced insulin resistance and deterioration of pancreatic beta cell function in adult offspring in mice (Yokomizo et al 2014), increased adult body weight and fat mass, increased blood glucose and cholesterol levels, and increased lipid deposition (Srinivasan et al 2006, Elahi et al 2009, Bringhenti et al 2013. Our results agree partially with this.…”

A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring

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