C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice

Immunobiology. 2013 Jan;218(1):127-33. doi: 10.1016/j.imbio.2012.04.001. Epub 2012 Apr 21.


Introduction: Acylation stimulating protein (ASP) is a hormone secreted by the adipose tissue that has been shown to increase triglyceride storage and glucose transport in adipocytes. These effects are mediated by C5L2 receptor, which has also been associated with inflammatory effects. C5L2 deficient mice on a low-fat diet are hyperphagic yet lean due to increased energy expenditure. The present study assessed insulin sensitivity and metabolic and inflammatory changes in C5L2KO mice vs WT in diet-induced obesity.

Methods: We placed C5L2KO and WT mice on a diabetogenic diet for 12 weeks and examined in vivo and ex vivo metabolism.

Results: C5L2KO mice on a diabetogenic diet exhibit decreased insulin sensitivity. Whole body substrate partitioning is evidenced through increased glucose uptake by the liver and decreased uptake by adipose tissue and skeletal muscle. Lipid content of both liver and skeletal muscle was higher in C5L2KO mice vs WT. Furthermore, elevated levels of macrophage markers were found in adipose tissue, liver and skeletal muscle of C5L2KO mice vs WT. Several inflammatory cytokines such as IL-6, MIP-1α and KC were also elevated in plasma of C5L2KO mice vs WT.

Conclusions: Overall, we demonstrated that C5L2KO mice fed a diabetogenic diet develop more severe insulin resistance than WT mice through altered substrate partitioning, ectopic fat deposition and a pro-inflammatory phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism*
  • Animals
  • Body Fat Distribution
  • Cells, Cultured
  • Complement C3
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diet / adverse effects
  • Inflammation Mediators / metabolism
  • Insulin Resistance / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Liver / immunology
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism*
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / immunology
  • Obesity / metabolism*
  • Receptor, Anaphylatoxin C5a
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism*
  • Triglycerides / genetics
  • Triglycerides / metabolism


  • C3 protein, mouse
  • C5ar2 protein, mouse
  • Complement C3
  • Cytokines
  • Inflammation Mediators
  • Intercellular Signaling Peptides and Proteins
  • Receptor, Anaphylatoxin C5a
  • Receptors, Chemokine
  • Triglycerides