The present study examined whether the perinephric and epididymal visceral fat (PEVF) depot under short-term excess nutrient protected the liver by trapping nutrient-derived nonesterified
free fatty acids (NEFAs) or had deleterious effects on hepatic
triglycerides (TGs) accumulation and
insulin resistance due to
adipokine secretion. Young rats pre-emptively underwent surgical PEVF removal or
sham operations and were fed with either high-fat diet (HFD) (PEVF-HFD) or regular chow (RC) (PEVF-RC) for 3 days.
Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Liver TG, serum
NEFA, and fat-derived
adipokines were assessed.
Insulin and lipogenesis signaling were assessed by western blots. Pre-emptive PEVF removal significantly decreases
insulin-induced suppression of hepatic
glucose production (HGP) both in RC and in HFD-fed rats. In accordance with the clamp results, hepatic TG accumulation is also significantly reduced by PEVF excision both in RC and HFD-fed rats. These results are further validated by
insulin signaling results, which show that pre-emptive PEVF removal increases phosphorylation of hepatic Akt, irrespective of diet. Notably, high levels of serum
leptin induced by HFD are significantly reduced by pre-emptive PEVF excision. Additionally, expression of lipogenic
enzyme p-
acetyl-CoA-carboxylase, denoting reduced lipogenesis, is increased in the PEVF-HFD rats. In conclusion, PEVF has a deleterious effect on the liver as a source of
insulin resistance-inducing
adipokines irrespective of diet, and does not serve as a
buffer for excess nutrients.