title: Relationship of C5L2 receptor to skeletal muscle substrate utilization.
abstract: OBJECTIVE
  To investigate the role of Acylation Stimulating Protein (ASP) receptor C5L2 in skeletal muscle fatty acid accumulation and metabolism as well as insulin sensitivity in both mice and human models of diet-induced insulin resistance.
  
  
  METHODS
  Male wildtype (WT) and C5L2 knockout (KO) mice were fed a low (LFD) or a high (HFD) fat diet for 10 weeks. Intramyocellular lipid (IMCL) accumulation (by oil red O staining) and beta-oxidation HADH enzyme activity were determined in skeletal muscle. Mitochondria were isolated from hindleg muscles for high-resolution respirometry. Muscle C5L2 protein content was also determined in obese type 2 diabetics and age- and BMI matched men.
  
  
  RESULTS
  IMCL levels were increased by six-fold in C5L2KO-HFD compared to WT-HFD mice (p<0.05) and plasma insulin levels were markedly increased in C5L2KO-HFD mice (twofold, p<0.05). Muscle HADH activity was elevated in C5L2KO-LFD mice (+75%, p<0.001 vs. WT-LFD) and C5L2KO-HFD displayed increased mitochondrial fatty acid oxidative capacity compared to WT-HFD mice (+23%, p<0.05). In human subjects, C5L2 protein content was reduced (-48%, p<0.01) in type 2 diabetic patients when compared to obese controls. Further, exercise training increased C5L2 (+45%, p = 0.0019) and ASP (+80%, p<0.001) in obese insulin-resistant men.
  
  
  CONCLUSIONS
  The results suggest that insulin sensitivity may be permissive for coupling of C5L2 levels to lipid storage and utilization.
authors: Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada.
authors: Christian
authors: C
authors: Roy
authors: Sabina
authors: S
authors: Paglialunga
authors: Gert
authors: G
authors: Schaart
authors: Esther
authors: E
authors: Moonen-Kornips
authors: Ruth C
authors: RC
authors: Meex
authors: Esther
authors: E
authors: Phielix
authors: Joris
authors: J
authors: Hoeks
authors: Matthijs K C
authors: MK
authors: Hesselink
authors: Katherine
authors: K
authors: Cianflone
authors: Patrick
authors: P
authors: Schrauwen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism; D015444:Exercise; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000097:blood / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: C417003:C5aR2 protein, human; C000594938:C5ar2 protein, mouse; D007328:Insulin; D017382:Reactive Oxygen Species; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine