Both Hepatic Lipogenesis and Beta-Oxidation are Altered in Offspring of Mothers Fed a High-Fat Diet in the First Two Generations (F1 and F2)

Abstract

SUMMARY:The high fat (HF) fed mothers may program susceptibility in offspring to chronic diseases and affect subsequent generations. The present study evaluated the liver structure in adulthood, focusing on the F1 and F2 generations. Females C57BL/6 (F0) were fed standard chow (SC) or HF diet (8 weeks) prior to mating and during the gestation and lactation to provide the F1 generation (SC-F1 and HF-F1). All other mothers and offspring fed SC. At 3 months old, F1 females were mated to produce the F2 generation (SC-F2 and HF-F2). The liver was kept in several fragments and prepared for histological analysis or frozen for biochemical and molecular analyzes. The F1 and F2 offspring were studied at 3 months old. HF-F1 had higher body mass (BM) compared to SC-F1 (P= 0.001), but not HF-F2 compared to SC-F2. HF-F1 had glucose intolerance when compared to SC-F1, but not HF-F2 compared to SC-F2. HF-F1 (P= 0.009) and HF-F2 (P= 0.03) showed hyperinsulinemia compared to their counterparts. Both groups HF-F1 and HF-F2 showed more steatosis than the SC counterparts (F1 and F2, P<0.0001). HF-F1 showed increased expression of PPAR-gamma and SREBP1-c compared to SC-F1 (P= 0.01). HF-F2 showed increased PPAR-gamma expression compared to SC-F2 (P= 0.04). In conclusion, HF-fed mother impairs both lipogenesis and beta-oxidation pathways in F1 through upregulation of PPAR-gamma and downregulation of PPAR-alpha. In F2, the only lipogenesis is enhanced, but it causes a disrupted PPAR balance, favoring the hepatic lipid accumulation and impaired metabolism in these animals that were not directly exposed to the maternal HF intake.

Transgenerational effects of obesogenic diets in rodents: A meta‐analysis

“…We found no significant effects on grand-offspring traits of treatment animals from one-off experiments, although the effect was in the expected direction. Others have shown that subtle effects of obesogenic diets can persist beyond the F0 generation even without further diet manipulation, [71][72][73][74] whereas our meta-analysis highlights that there is uncertainty and heterogeneity regarding this effect. In contrast, grand-offspring traits of treatment animals from multigenerational experiments were 43% higher than their control counterparts.…”

“…Grand-offspring traits of treatment animals from One-off experiments tended to be 9% higher than control grand-offspring, although this overall effect was statistically non-significant. This finding is unsurprising, as it has been previously shown that subtle effects of obesogenic diets can persist beyond the F0 generation even without further diet manipulation [71][72][73][74] .…”