Paternal high-fat diet influences the high-fat diet-induced hypermethylation of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha promoter in the offspring of C57BL/6 mice

Abstract

Objective To determine the effects of high-fat diet on metabolic health outcomes in their male offspring and methylated regulation of the metabolic master regulator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) in C57BL/6 mice. Methods 8-week-old C57BL/6 male mice (n=20) were divided into two groups: the standard chow group (C, n=10) and the high fat diet group (HF, n=10) with random number table. After 12 weeks high fat diet (HFD) feed, each male mouse mated with a female sibling. Male pups were divided into two groups: male offspring from the control group (CM, n=8) and male offspring from HF group (HFM, n=9) were given HFD for 4 weeks until sacrifice at 8 weeks of age.The experimental data were analyzed by t test between two groups. Results Compared with CM group, 4 weeks HFD resulted in a significantly increase in HFM in body weight 3.27% (t=-3.924, P<0.01), fat pad mass[(2.26±0.24)% vs (3.67±0.52)%, t=-3.906, P<0.01] and impaired glucose tolerance. Blood glucose in 15 min were (328±26) vs (410±53) mg/dl, 30 min were (318±43) vs (412±48) mg/dl, 60 min were (248±31) vs (328±32) mg/dl and area under the curve were (374±39) mg/dl×120 min vs (388±33) mg/dl×120 min (t=-2.291, -3.656, -4.759, -4.753, all P<0.01). Meanwhile, paternal HFD can increase the HFD-induced methylation of the Pgc-1α promoter were (36.8±4.7)% vs (44.3±3.6)% (t=-4.453, P<0.01) with a trend of decreased Pgc-1α mRNA expression in skeletal muscle. Conclusions The current study provides the evidence that paternal obesity can increase susceptibility to HFD-induced obesity and glucose tolerance dysfunction in male offspring with hypermethylation of the Pgc-1α promoter at CpG site-260. Key words: Paternalobesity; Male pup; Metabolic healthy; Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; DNA methylation