Mullen Kerry L, Smith Angela C, Junkin Kathryn A, Dyck David J
Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada, N1G 2W1.
Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E83-90. doi: 10.1152/ajpendo.00545.2006. Epub 2007 Mar 13.
High-fat (HF) diets induce insulin resistance and alter lipid metabolism, although controversy exists regarding the impact of saturated vs. polyunsaturated fats. Adiponectin (Ad) stimulates fatty acid (FA) oxidation and improves insulin sensitivity in humans and rodents, due in part to the activation of AMP-activated protein kinase (AMPK) and subsequent deactivation of acetyl coenzyme A carboxylase (ACC). In genetically obese, diabetic mice, this acute stimulatory effect on AMPK in muscle is lost. The ability of a HF diet to induce skeletal muscle Ad resistance has not been examined. The purpose of this study was to determine whether Ad's effects on FA oxidation and AMPK/ACC would be reduced following different HF diets, and if this coincided with the development of impaired maximal insulin-stimulated glucose transport. Rats were fed a control (10% kcal fat, CON), high unsaturated fat (60% kcal safflower oil, SAFF), or high saturated fat diet (60% kcal lard, LARD) for 4 wk. Following the dietary intervention, glucose transport, lipid metabolism, and AMPK/ACC phosphorylation were measured in the presence and absence of globular Ad (gAd, 2.5 microg/ml) in isolated soleus muscle. LARD rats showed reduced rates of maximal insulin-stimulated glucose transport compared with CON and SAFF (+68 vs. +172 and +184%, P < or = 0.001). gAd increased pACC (+25%, P < or = 0.01) and FA oxidation (+28%, P < or = 0.05) in CON rats, but not in either HF group. Thus 4 wk of HF feeding results in the loss of gAd stimulatory effect on ACC phosphorylation and muscle FA oxidation, and this can occur independently of impaired maximal insulin-stimulated glucose transport.
高脂（HF）饮食会诱发胰岛素抵抗并改变脂质代谢，尽管关于饱和脂肪与多不饱和脂肪的影响仍存在争议。脂联素（Ad）可刺激脂肪酸（FA）氧化并改善人和啮齿动物的胰岛素敏感性，部分原因是激活了AMP活化蛋白激酶（AMPK）并随后使乙酰辅酶A羧化酶（ACC）失活。在遗传性肥胖的糖尿病小鼠中，这种对肌肉中AMPK的急性刺激作用丧失。尚未研究HF饮食诱导骨骼肌Ad抵抗的能力。本研究的目的是确定在不同的HF饮食后，Ad对FA氧化和AMPK/ACC的作用是否会降低，以及这是否与最大胰岛素刺激的葡萄糖转运受损的发展相一致。将大鼠喂食对照饮食（10%千卡脂肪，CON）、高不饱和脂肪饮食（60%千卡红花油，SAFF）或高饱和脂肪饮食（60%千卡猪油，LARD）4周。饮食干预后，在离体比目鱼肌中存在和不存在球状Ad（gAd，2.5微克/毫升）的情况下，测量葡萄糖转运、脂质代谢和AMPK/ACC磷酸化。与CON和SAFF组相比，LARD组大鼠最大胰岛素刺激的葡萄糖转运速率降低（分别为+68%对+172%和+184%，P≤0.001）。gAd使CON组大鼠的pACC增加（+25%，P≤0.01）和FA氧化增加（+28%，P≤0.05），但在任何一个HF组中均未增加。因此，4周的HF喂养导致gAd对ACC磷酸化和肌肉FA氧化的刺激作用丧失，并且这可能独立于最大胰岛素刺激的葡萄糖转运受损而发生。
