1653-P: Female Mice Are Protected from Deleterious Metabolic Programming Effects of a High-Fat Diet Fed during Pregnancy and Lactation

Obesity induced by a high fat (HF) diet during pregnancy (P) and lactation (L) shows a sexual dimorphic response in offspring. Studies reported a metabolic benefit for female compared to male offspring. The mechanisms that determine sexual dimorphic responses are still poorly understood. This study investigates the metabolic phenotype, adipose tissue distribution and hepatic lipid metabolism in female offspring exposed to a HF diet during P/L and early adulthood. CD1 female offspring mice were exposed to either a control (C) or a HF diet during P/L and fed a regular chow after weaning for 23 wks and then re-exposed to either the C or HF diet for 19 wks. This resulted into mice exposed to the C diet during P/L and re-exposed to either the C (C-C) or HF (C-H) diet, and mice exposed to the HF diet during P/L and re-exposed to either the C (H-C) or HF (H-H) diet (n=3-5). Body weight (BW), body composition, food intake (FI), fasted blood glucose and insulin levels, intra peritoneal glucose (ipGTT) and insulin (ipITT) tolerance were measured. Mice were sacrificed at 45 wks and qRT-PCR of stearoyl-CoA-desaturase 1 (SCD-1) as a marker of lipogenesis and of caveolin-1 (CAV1) as a protective marker of hepatic steatosis was performed in liver. BW, adiposity and ipGTT and ipITT were not different between C-H and H-H. However adiposity was increased 3.0-fold in C-H compared to C-C and 2.0-fold in H-H compared to H-C, respectively (both p<0.05). FI and fasted glucose and insulin were not different between groups. Gene expression of SCD-1 was downregulated by 69% in C-H compared to C-C and by 81% in H-H compared to H-C, respectively, (both p<0.05) in liver. In contrast, hepatic CAV1 gene expression was increased 1.93-fold in H-H compared to H-C (p<0.05). These data show that female mice are protect from the deleterious programming effects of a HF diet. Moreover, mice exposed to a HF diet during P/L exhibit protective mechanisms to prevent hepatic steatosis when re-exposed to HF diet in early adulthood.