Recovered insulin response by 2 weeks of leptin administration in high-fat fed rats is associated with restored AS160 activation and decreased reactive lipid accumulation

作者：Stefanyk Leslie E; Gulli Roberto A; Ritchie Ian R; Chabowski Adrian; Snook Laelie A; Bonen Arend; Dyck David J^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2011, 301(1): R159-R171.

DOI：10.1152/ajpregu.00636.2010

• fatty acid transport proteins
• insulin signaling
• diacylglycerol
• ceramide
• mitochondria
• leptin

Stefanyk LE, Gulli RA, Ritchie IR, Chabowski A, Snook LA, Bonen A, Dyck DJ. Recovered insulin response by 2 weeks of leptin administration in high-fat fed rats is associated with restored AS160 activation and decreased reactive lipid accumulation. Am J Physiol Regul Integr Comp Physiol 301: R159-R171, 2011. First published April 27, 2011; doi:10.1152/ajpregu.00636.2010.-Leptin is an adipokine that increases fatty acid (FA) oxidation, decreases intramuscular lipid stores, and improves insulin response in skeletal muscle. In an attempt to elucidate the underlying mechanisms by which these metabolic changes occur, we administered leptin (Lep) or saline (Sal) by miniosmotic pumps to rats during the final 2 wk of a 6-wk low-fat (LF) or high-fat (HF) diet. Insulin-stimulated glucose transport was impaired by the HF diet (HF-Sal) but was restored with leptin administration (HF-Lep). This improvement was associated with restored phosphorylation of Akt and AS160 and decreased in reactive lipid species (ceramide, diacylglycerol), known inhibitors of the insulin-signaling cascade. Total muscle citrate synthase (CS) activity was increased by both leptin and HF diet, but was not additive. Leptin increased subsarcolemmal (SS) and intramyofibrillar (IMF) mitochondria CS activity. Total muscle, sarcolemmal, and mitochondrial (SS and IMF) FA transporter (FAT/CD36) protein content was significantly increased with the HF diet, but not altered by leptin. Therefore, the decrease in reactive lipid stores and subsequent improvement in insulin response, secondary to leptin administration in rats fed a HF diet was not due to a decrease in FA transport protein content or altered cellular distribution.

• 出版日期2011-7