Abstract
BackgroundMusclin is a novel skeletal muscle-derived secretory factor considered to be a potent regulator of the glucose metabolism and therefore may contribute to the pathogenesis of obesity and insulin resistance (IR).MethodsTo test this hypothesis, we examined the plasma musclin levels in overweight/obese subjects and lean controls. Rats on a high fat diet (HFD) were used as the annimal model of obesity. Radioimmunoassay and western blot were used to determine musclin levels in plasma and skeletal muscle.ResultsAccording to radioimmunoassays,the overweight/obese subjects exhibited elevated musclin plasma levels compared with the lean controls (89.49 ± 19.00 ng/L vs 80.39 ± 16.35 ng/L, P < 0.01). The musclin levels were positively correlated with triglyceride, fasting plasma glucose, and homeostasis model assessment of IR levels. These observations were confirmed with a high-fat diet(HFD) rat model. HFD rats also exhibited increased musclin immunoreactivity in plasma (P < 0.01) and in skeletal muscle (P < 0.05), as well as increased musclin mRNA levels in skeletal muscle (P < 0.01). Musclin incubation significantly inhibited muscles 3H-2-DG uptake in the normal diet(ND) group (P < 0.01). The protein expression of glucose transporter type 4 was significantly down regulated by 30% (P < 0.05) in the ND group after soleusmuscle was incubated with musclin compared with the control. Musclin incubation also increased the protein levels of glucose-regulated protein (GRP)78 and GRP94 by 146.8 and 54% (both P < 0.05), respectively, in ND rats.ConclusionsOur data support the hypothesis that musclin has a strong relationship with obesity-associated IR by impairing the glucose metabolism and, at least in part, through causing endoplasmic reticulum stress.
Highlights
Musclin is a novel skeletal muscle-derived secretory factor considered to be a potent regulator of the glucose metabolism and may contribute to the pathogenesis of obesity and insulin resistance (IR)
Plasma musclin levels were not associated with BMI, Diastolic blood pressure (DBP), SBP, or the other variables
The present study demonstrated for the first time that plasma musclin levels were significantly higher in subjects with obesity than in lean controls
Summary
Musclin is a novel skeletal muscle-derived secretory factor considered to be a potent regulator of the glucose metabolism and may contribute to the pathogenesis of obesity and insulin resistance (IR). The precise mechanism linking obesity to IR and T2DM are unknown, extensive evidence suggests that impaired glucose disposal in skeletal muscle plays a crucial role in development of obesity-associated disease [2]. Nishizawa et al reported that musclin mRNA expression was augmented in the skeletal muscle of obese mice [9]. Musclin has been shown to be a novel, endogenous obesity-related factor in animal models, the mechanism of its bioactivity and its expression in humans remain largely unknown
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