Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity.

摘要: Rats selectively bred for high endurance running capacity (HCR) have higher insulin sensitivity and improved metabolic health compared with those low (LCR). We investigated several skeletal muscle characteristics, in vitro vivo, that could contribute to the phenotypes observed sedentary LCR HCR rats. After 16 generations of selective breeding, had approximately 400% (P < 0.001), lower fasting plasma glucose triglycerides 0.05) LCR. Skeletal ceramide diacylglycerol content, basal AMP-activated protein kinase (AMPK) activity, lipolysis were similar between HCR. However, stimulation response 10 μm isoproterenol was 70% = 0.004). Impaired associated triacylglycerol lipase Ser660 phosphorylation HSL, β2-adrenergic receptor content muscle. Expression orphan nuclear Nur77, which is induced by β-adrenergic signaling sensitivity, 0.05). Muscle Nur77 target genes, including uncoupling 3, fatty acid translocase/CD36, AMPK γ3 subunit also Our investigation associates whole-body resistance impaired reduced expression genes are critical regulators lipid metabolism identify signal transduction as a potential mechanism after artificial selection intrinsic exercise capacity.