Effect of Adipose Differentiation-Related Protein (ADRP) on Glucose Uptake of Skeletal Muscle

Abstract

Background: Skeletal muscle is the most important tissue contributing to insulin resistance. Several studies have shown that accumulation of intramyocellular lipid is associated with the development of insulin resistance. Thus, proteins involved in lipid transport, storage and metabolism might also be involved in insulin action in skeletal muscle. Adipose differentiation-related protein (ADRP), which is localized at the surface of lipid droplets, is known to be regulated by peroxisome proliferator activated receptor γ (PPARγ). However, it is not known whether ADRP plays a role in regulating glucose uptake and insulin action in skeletal muscle. Methods: ADRP expression in skeletal muscle was measured by RT-PCR and western blot in db/db mice with and without PPARγ agonist. The effect of PPARγ agonist or high lipid concent ration (0.4% intralipos) on ADRP expression was also obtained in cultured human skeletal mu scle cells. Glucose uptake was measured when ADRP was down-regulated with siRNA or when ADRP was overexpressed with adenovirus. Results: ADRP expression increased in the skeletal muscle of db/db mice in comparison with normal controls and tended to increase with the treatment of PPARγ agonist. In cultured human skeletal muscle cells, the treatment of PPARγ agonist or high lipid concentration increased ADRP expression. siADRP treatment decreased both basal and insulin-stimulated glucose uptake whereas ADRP overexpression increased glucose uptake in cultured human skeletal muscle cells. Conclusion: ADRP expression in skeletal muscle is increased by PPARγ agonist or exposure to high lipid concentration. In these conditions, increased ADRP contributed to increase glucose uptake. These results suggest that insulin-sensitizing effects of PPARγ are at least partially achieved by the increase of ADRP expression, and ADRP has a protective effect against intramyoce llular lipid-induced insulin resistance. (Korean Diabetes J 33:206-214, 2009)