Effect And Potential Mechanisms Of Maternal High-Fat Diet On The Metabolic Characteristics Of Offspring

Objective:High-fat diet always induced obesity and other metabolic disorders, and abnormal regulation of neural pathways in the hypothalamic is a key factor in the phenomenon. In general, offspring of obese mothers are more susceptible to obesity and other metabolic diseases.However, whether mother obesity will influence children neuromodulation pathways of the hypothalamus for regulating food intake remains an obscure issue. In the study, we try to explore whether maternal overweight and obesity induced by high-fat diet feeding contributed to affecting the susceptibility to develop obesity in the offspring and the potential molecular mechanisms.Methods:Female SD rats were allowed to either high-fat diet (HFD) or normal chow diet (LFD) for 14 weeks, and then mated with healthy male rats. The offspring born to HFD or LFD dams (designated as HFD-O or LFD-O) were assigned to normal chow diet. Birth weight and body weight of HFD-O and LFD-O were measured. Body compositions of offspring were confirmed by microCT. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin sensitivity. Daily food intakes were routinely recorded for 10 days in both childhood (P30-P40) and adulthood (P150-P160). Animals were sacrificed at postnatal day 40 and 160 (P40 and P160), and serum and tissue samples were collected. Serum lipid levels were detection by biochemical analysis, and ELISA kits for insulin and hypothalamus-pituitary-adrenal Axle hormone were tested respectively. The characteristics of orexigenic NPY (Neuorpeptide Y) and anorexigenic POMC (Proopiomelanocortin) expression in the hypothalamaus were determined by immunohistochemical staining. Gene expression levels under hypothalamic were determined by Real-Time PCR. H&E staining were performed in brown adipose tissue.Results:High-fat diet induced generation of obesity. Compared with LFD-O, HFD-O got higher birth weight, and higher body weight during childhood and adulthood regardless of male and female.And also higher in body fat content as HFD-O increased gonadal fat pad weight during childhood and adulthood compared with LFD-O. GTT indicated impaired glucose tolerance in HFD-O, but insulin sensitivity is not damaged. HFD-O took more food than LFD-O in childhood but not adulthood. Immunohistochemical staining showed the NPY levels were increased in the hypothalamic arcuate nucleus of HFD-O compared with LFD-O, but there was no significant change of POMC expression between the groups, both during childhood and adulthood. There was no change in serum lipid levels and hypothalamus-pituitary-adrenal axle hormone. H&E staining showed more and larger lipid droplets were fund in brown adipose tissue cells of HFD-O.Conclusion:High-fat diet induced maternal overweight and obesity predisposes obese and metabolic diseases development in the offspring, which may possibly be associated with the altered hypothalamic feeding neural pathways and dysfunction of brown adipose tissue. Pregnancy weight management is important to prevent obese and metabolic diseases form the source. Control Pregnancy weight effectively may improve the health of mother and child two generations.