Perinephric and Epididymal Fat Affect Hepatic Metabolism in Rats
Perinephric and Epididymal Fat Affect Hepatic Metabolism in Rats
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DOI：
10.1038/oby.2011.261
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发表时间：
2012-01-01
期刊：
影响因子：
6.9
通讯作者：
Fishman, Sigal
中科院分区：
文献类型：
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作者：
Ben-Shlomo, Shani;Einstein, Francine H.;Fishman, Sigal
本研究探讨了短期营养过剩下的肾周和附睾内脏脂肪（PEVF）储存是否通过捕获营养来源的非酯化游离脂肪酸（NEFAs）来保护肝脏，还是由于脂肪因子的分泌而对肝脏甘油三酯（tg）积累和胰岛素抵抗产生有害影响。幼龄大鼠预先接受手术切除PEVF或假手术，并饲喂高脂饲料（HFD） （PEVF-HFD）或常规饲料（PEVF-RC） 3天。采用高胰岛素-正糖钳法测定胰岛素敏感性。评估肝脏TG、血清NEFA和脂肪源性脂肪因子。western blots检测胰岛素和脂肪生成信号。在RC和hfd喂养的大鼠中，预先去除PEVF显著降低胰岛素诱导的肝糖生成（HGP）抑制。根据钳夹结果，在RC和hfd喂养的大鼠中，PEVF切除也显著减少了肝脏TG积累。胰岛素信号传导结果进一步验证了这些结果，该结果表明，无论饮食如何，抢先去除PEVF都会增加肝脏Akt的磷酸化。值得注意的是，HFD诱导的高水平血清瘦素通过先发制人的PEVF切除而显著降低。此外，PEVF-HFD大鼠脂肪生成酶对乙酰辅酶a羧化酶的表达增加，表明脂肪生成减少。综上所述，无论饮食如何，PEVF作为胰岛素抵抗诱导脂肪因子的来源对肝脏有有害影响，并且不能作为过量营养物质的缓冲。
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.