Perinephric and Epididymal Fat Affect Hepatic Metabolism in Rats

• Published in: Obesity (Silver Spring, Md.) Md.), 2012-01, Vol.20 (1), p.151-156
• Main Authors: Ben‐Shlomo, Shani, Einstein, Francine H., Zvibel, Isabel, Atias, Dikla, Shlomai, Amir, Halpern, Zamir, Barzilai, Nir, Fishman, Sigal
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Blotting, Western; Body fat; Diet, High-Fat - adverse effects; Epididymis; Fatty Acids, Nonesterified - metabolism; Fatty Liver - etiology; Fatty Liver - metabolism; Insulin Resistance; Intra-Abdominal Fat - metabolism; Kidney; Liver; Liver - metabolism; Male; Metabolism; Non-alcoholic Fatty Liver Disease; Obesity - complications; Obesity - metabolism; Phosphorylation; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction; Triglycerides - metabolism
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2011.261

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.