Hegarty Bronwyn D, Cooney Gregory J, Kraegen Edward W, Furler Stuart M
Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Diabetes. 2002 May;51(5):1477-84. doi: 10.2337/diabetes.51.5.1477.
In humans and animal models, increased lipid content of skeletal muscle is strongly associated with insulin resistance. However, it is unclear whether this accumulation is due to increased uptake or reduced utilization of fatty acids (FAs). We used (3)H-R-bromopalmitate tracer to assess the contribution of tissue-specific changes in FA uptake to the lipid accumulation observed in tissues of insulin-resistant, high fat-fed rats (HFF) compared with control rats (CON) fed a standard diet. To study FA metabolism under different metabolic states, tracer was infused under basal conditions, during hyperinsulinemic-euglycemic clamp (low FA availability) or during the infusion of intralipid and heparin (high FA availability). FA clearance was significantly increased in the red gastrocnemius muscle of HFF under conditions of low (HFF = 10.4 +/- 1.1; CON = 7.4 +/- 0.5 ml x min(-1) x 100 g(-1); P < 0.05), basal (HFF = 8.3 +/- 1.4; CON = 4.5 +/- 0.7 ml x min(-1) x 100 g(-1); P < 0.01), and high (HFF = 7.0 +/- 0.8; CON = 4.3 +/- 0.5 ml x min(-1) x 100 g(-1); P < 0.05) FA levels. This indicates an adaptation by muscle for more efficient uptake of lipid. Associated with the enhanced efficiency of FA uptake, we observed increases in CD36/FA translocase mRNA expression (P < 0.01) and acyl-CoA synthetase activity (P < 0.02) in the same muscle. FA clearance into white adipose tissue was also increased in HFF when circulating FA were elevated, but there was little effect of the high-fat diet on hepatic FA uptake. In conclusion, insulin resistance induced by feeding rats a high-fat diet is associated with tissue-specific adaptations that enhance utilization of increased dietary lipid but could also contribute to the accumulation of intramuscular lipid with a detrimental effect on insulin action.
在人类和动物模型中，骨骼肌脂质含量增加与胰岛素抵抗密切相关。然而，尚不清楚这种蓄积是由于脂肪酸（FAs）摄取增加还是利用减少所致。我们使用³H-R-溴棕榈酸示踪剂，评估在高脂肪喂养的胰岛素抵抗大鼠（HFF）组织中观察到的脂质蓄积中，脂肪酸摄取的组织特异性变化与喂食标准饮食的对照大鼠（CON）相比所起的作用。为研究不同代谢状态下的脂肪酸代谢，在基础条件下、高胰岛素-正常血糖钳夹期间（低脂肪酸可用性）或输注脂质乳剂和肝素期间（高脂肪酸可用性）注入示踪剂。在低（HFF = 10.4 ± 1.1；CON = 7.4 ± 0.5 ml·min⁻¹·100 g⁻¹；P < 0.05）、基础（HFF = 8.3 ± 1.4；CON = 4.5 ± 0.7 ml·min⁻¹·100 g⁻¹；P < 0.01）和高（HFF = 7.0 ± 0.8；CON = 4.3 ± 0.5 ml·min⁻¹·100 g⁻¹；P < 0.05）脂肪酸水平条件下，HFF大鼠的红色腓肠肌中脂肪酸清除率显著增加。这表明肌肉为更有效地摄取脂质而产生了适应性变化。与脂肪酸摄取效率增强相关，我们观察到同一块肌肉中CD36/脂肪酸转位酶mRNA表达增加（P < 0.01）以及酰基辅酶A合成酶活性增加（P < 0.02）。当循环脂肪酸升高时，HFF大鼠白色脂肪组织中的脂肪酸清除率也增加，但高脂饮食对肝脏脂肪酸摄取几乎没有影响。总之，给大鼠喂食高脂饮食诱导的胰岛素抵抗与组织特异性适应性变化有关，这些变化增强了对增加的膳食脂质的利用，但也可能导致肌肉内脂质蓄积，对胰岛素作用产生不利影响。
