Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR alpha in adipocytes have been unclarified. We examined the functions of PPAR alpha using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR alpha by GW7647, a potent PPAR alpha agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR gamma, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR alpha activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR gamma is activated. On the other hand, PPAR alpha activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR alpha-dependent manner. Moreover, PPAR alpha activation increased the production of CO2 and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR alpha stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR alpha agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPAR alpha activation are very valuable for managing diabetic conditions accompanied by obesity, because PPAR gamma agonists, usually used as antidiabetic drugs, induce excessive lipid accumulation in adipocytes in addition to improvement of insulin resistance. (C) 2011 Elsevier Inc. All rights reserved.