Expression of human chemerin induces insulin resistance in the skeletal muscle but does not affect weight, lipid levels, and atherosclerosis in LDL receptor knockout mice on high-fat diet.
OBJECTIVE
Chemerin is a recently discovered hepatoadipokine that regulates adipocyte differentiation as well as chemotaxis and activation of dendritic cells and macrophages. Chemerin was reported to modulate insulin sensitivity in adipocytes and skeletal muscle cells in vitro and to exacerbate glucose intolerance in several mouse models in vivo. In humans, chemerin was shown to be associated with multiple components of the metabolic syndrome including BMI, triglycerides, HDL cholesterol, and hypertension. This study aimed to examine the effect of chemerin on weight, glucose and lipid metabolism, as well as atherosclerosis in vivo.


METHODS
We used recombinant adeno-associated virus to express human chemerin in LDL receptor knockout mice on high-fat diet.


RESULTS
Expression of chemerin did not significantly alter weight, lipid levels, and extent of atherosclerosis. Chemerin, however, significantly increased glucose levels during the intraperitoneal glucose tolerance test without affecting endogenous insulin levels and the insulin tolerance test. Chemerin reduced insulin-stimulated Akt1 phosphorylation and activation of 5'AMP-activated protein kinase (AMPK) in the skeletal muscle, but had no effect on Akt phosphorylation and insulin-stimulated AMPK activation in the liver and gonadal adipose tissue.


CONCLUSIONS
Chemerin induces insulin resistance in the skeletal muscle in vivo. Chemerin is involved in the cross talk between liver, adipose tissue, and skeletal muscle.
Becker
Melanie
M
Department of Internal Medicine II, University of Munich, Munich, Germany.
Rabe
Katja
K
Lebherz
Corinna
C
Zugwurst
Julia
J
Göke
Burkhard
B
Parhofer
Klaus G
KG
Lehrke
Michael
M
Broedl
Uli C
UC
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D018925:Chemokines / Q000097:blood / Q000235:genetics* / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000172:deficiency*
D001786:Blood Glucose; D018925:Chemokines; D004041:Dietary Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D055372:AMP-Activated Protein Kinases