Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle

doi:10.1074/jbc.M702329200

	Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle
	Kraemer, David Kitz ; Al-Khalili, Lubna ; Guigas, Bruno ; Leng, Ying; Garcia-Roves, Pablo M.; Krook, Anna
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2007-07-06
卷号	282 期号:27 页码:19313-19320
ISSN号	0021-9258
DOI	10.1074/jbc.M702329200
文献子类	Article
英文摘要	The peroxisome proliferator-activated receptor (PPAR)delta has been implicated in the regulation of lipid metabolism in skeletal muscle. Furthermore, activation of PPAR delta has been proposed to improve insulin sensitivity and reduce glucose levels in animal models of type 2 diabetes. We recently demonstrated that the PPAR delta agonist GW501516 activates AMP-activated protein kinase ( AMPK) and stimulates glucose uptake in skeletal muscle. However, the underlying mechanism remains to be clearly identified. In this study, we first confirmed that incubation of primary cultured human muscle cells with GW501516 induced AMPK phosphorylation and increased fatty acid transport and oxidation and glucose uptake. Using small interfering RNA, we have demonstrated that PPAR delta expression is required for the effect of GW501516 on the intracellular accumulation of fatty acids. Furthermore, we have shown that the subsequent increase in fatty acid oxidation induced by GW501516 is dependenton both PPAR delta and AMPK. Concomitant with these metabolic changes, we provide evidence that GW501516 increases the expression of key genes involved inlipid metabolism(FABP3, CPT1, and PDK4) by a PPAR delta-dependent mechanism. Finally, we have also demonstrated that the GW501516-mediated increase in glucose uptake requires AMPK but not PPAR alpha. In conclusion, the PPAR delta agonist GW501516 promotes changes in lipid/glucose metabolism and gene expression in human skeletal muscle cells by PPAR delta- and AMPK-dependent and -independent mechanisms.
WOS关键词	ACTIVATED-RECEPTOR-DELTA ; SINGLE NUCLEOTIDE POLYMORPHISMS ; PROTEIN-KINASE ; GENE-EXPRESSION ; FATTY-ACIDS ; COMPLEX I ; ALPHA ; PHOSPHORYLATION ; TRANSPORT ; OBESITY
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000247650600006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273203]
专题	中国科学院上海药物研究所
通讯作者	Krook, Anna
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China 3.Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden 4.Karolinska Inst, Dept Mol Med, SE-17177 Stockholm, Sweden 5.Karolinska Inst, Dept Surg, SE-17177 Stockholm, Sweden 6.Univ Catholique Louvain, Sch Med, Hormone & Metab Res Unit, B-1200 Brussels, Belgium 7.Inst Cellular Pathol, B-1200 Brussels, Belgium
推荐引用方式 GB/T 7714	Kraemer, David Kitz,Al-Khalili, Lubna,Guigas, Bruno,et al. Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2007,282(27):19313-19320.
APA	Kraemer, David Kitz,Al-Khalili, Lubna,Guigas, Bruno,Leng, Ying,Garcia-Roves, Pablo M.,&Krook, Anna.(2007).Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle.JOURNAL OF BIOLOGICAL CHEMISTRY,282(27),19313-19320.
MLA	Kraemer, David Kitz,et al."Role of AMP kinase and PPAR delta in the regulation of lipid and glucose metabolism in human skeletal muscle".JOURNAL OF BIOLOGICAL CHEMISTRY 282.27(2007):19313-19320.