Abstract:
:Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR agonist increases the uptake, distribution into complex cellular lipids, and oxidation of palmitate as well as the uptake and oxidation of glucose in cultured human skeletal muscle cells. Furthermore, the effect of the LXR agonist was additive to acute effects of insulin on palmitate uptake and metabolism. Consistently, activation of LXRs induced the expression of relevant genes: fatty acid translocase (CD36/FAT), glucose transporters (GLUT1 and -4), sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor-gamma, carnitine palmitoyltransferase-1, and uncoupling protein 2 and 3. Interestingly, in response to activation of LXRs, myotubes from patients with type 2 diabetes showed an elevated uptake and incorporation of palmitate into complex lipids but an absence of palmitate oxidation to CO(2). These results provide evidence for a functional role of LXRs in both lipid and glucose metabolism and energy uncoupling in human myotubes. Furthermore, these data suggest that increased intramyocellular lipid content in type 2 diabetic patients may involve an altered response to activation of components in the LXR pathway.
journal_name
Diabetesjournal_title
Diabetesauthors
Kase ET,Wensaas AJ,Aas V,Højlund K,Levin K,Thoresen GH,Beck-Nielsen H,Rustan AC,Gaster Mdoi
10.2337/diabetes.54.4.1108subject
Has Abstractpub_date
2005-04-01 00:00:00pages
1108-15issue
4eissn
0012-1797issn
1939-327Xpii
54/4/1108journal_volume
54pub_type
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