Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway.

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

Diabetes

journal_title

Diabetes

authors

Kase ET,Wensaas AJ,Aas V,Højlund K,Levin K,Thoresen GH,Beck-Nielsen H,Rustan AC,Gaster M

doi

10.2337/diabetes.54.4.1108

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

1108-15

issue

4

eissn

0012-1797

issn

1939-327X

pii

54/4/1108

journal_volume

54

pub_type

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