Paternal hyperglycemia in rats exacerbates the development of obesity in offspring.
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Parental history with obesity or diabetes will increase the risk for developing metabolic diseases in offspring. However, literatures as to transgenerational inheritance of metabolic dysfunctions through male lineage are relatively scarce. In the current study, we aimed to evaluate influences of paternal hyperglycemia on metabolic phenotypes in offspring. Male SD rats were i.p. injected with streptozotocin (STZ) or citrate buffer (CB, as control). STZ-injected rats with glucose levels higher than 16.7mM were selected to breed with normal female rats. Offspring from STZ or CB treated fathers (STZ-O and CB-O) were maintained in the identical condition. We monitored body weight and food intake, and tests of glucose and insulin tolerance (GTTs and ITTs), fasting-refeeding and cold exposure were performed. Expression of factors involved in hypothalamic feeding and brown adipose tissue (BAT) thermogenic activity was performed by real-time PCR and Western blot. Adult STZ-O were heavier than CB-O. Impairment of GTTs was observed in STZ-O compared with CB-O at 22 and 32 weeks of age; ITTs results showed decreased insulin sensitivity in STZ-O. Daily food intake and accumulated food intake during 12-h refeeding after fasting were significantly higher in STZ-O. UCP1 levels were downregulated in BAT from STZ-O at room temperature and cold exposure. Finally, STZ-O rats showed suppressed leptin signaling in the hypothalamus as evidenced by upregulated SOCS3, reduced phosphorylation of STAT3, impaired processing POMC and decreased -MSH production. Our study revealed that paternal hyperglycemia predisposes offspring to developing obesity, which is possibly associated with impaired hypothalamic leptin signaling.
author list (cited authors)
Shi, X., Li, X., Hou, Y. i., Cao, X., Zhang, Y., Wang, H., ... Xiao, X.
complete list of authors
Shi, Xiaoqin||Li, Xinyu||Hou, Yi||Cao, Xuemei||Zhang, Yuyao||Wang, Heng||Wang, Hongyin||Peng, Chuan||Li, Jibin||Li, Qifu||Wu, Chaodong||Xiao, Xiaoqiu