title: 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 β-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 β-cell function may be related partially to increases in oxidative stress in male islets and decreased plasma estradiol levels in males.
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yokomizo
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan; and toyoshi@intmed3.med.kyushu-u.ac.jp.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Inoguchi
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan; and.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sonoda
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sakaki
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hirata
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takei
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Noriko
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Division of Epigenomics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Division of Epigenomics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology; D012737:Sex Factors
chemical_list: D004041:Dietary Fats
keywords: high-fat diet; insulin resistance; maternal exposure; oxidative stress; type 2 diabetes