title: Perinephric and epididymal fat affect hepatic metabolism in rats.
abstract: 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.
authors.affiliation: The Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Ben-Shlomo
authors.forename: Francine H
authors.initials: FH
authors.lastname: Einstein
authors.forename: Isabel
authors.initials: I
authors.lastname: Zvibel
authors.forename: Dikla
authors.initials: D
authors.lastname: Atias
authors.forename: Amir
authors.initials: A
authors.lastname: Shlomai
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.forename: Sigal
authors.initials: S
authors.lastname: Fishman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D004822:Epididymis; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007668:Kidney; D008099:Liver / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides