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SHR Neuro Cancer Cardio Lipid

Wolf, D; Bukosza, N; Engel, D; Poggi, M; Jehle, F; Anto Michel, N; Chen, YC; Colberg, C; Hoppe, N; Dufner, B; Boon, L; Blankenbach, H; Hilgendorf, I; von Zur Muhlen, C; Reinöhl, J; Sommer, B; Marchini, T; Febbraio, MA; Weber, C; Bode, C; Peter, K; Lutgens, E; Zirlik, A.
Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11b/CD18) in diet-induced obesity (DIO).
Thromb Haemost. 2017; 117(2):325-338
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Authors Med Uni Graz:
Anto Michel Nathaly
Zirlik Andreas
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Abstract:
Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1's adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antibodies, Monoclonal - pharmacology
CD11b Antigen - deficiency
CD11b Antigen - genetics
CD11b Antigen - metabolism
CD18 Antigens - deficiency
CD18 Antigens - genetics
CD18 Antigens - metabolism
Cell Adhesion -
Cells, Cultured -
Chemotaxis - drug effects
Cytokines - metabolism
Diet - adverse effects
Disease Models, Animal -
Genotype -
Hyperlipidemias - genetics
Hyperlipidemias - metabolism
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Insulin Resistance -
Intra-Abdominal Fat - drug effects
Intra-Abdominal Fat - metabolism
Intra-Abdominal Fat - pathology
Leukocytes - drug effects
Leukocytes - metabolism
Leukocytes - pathology
Macrophage-1 Antigen - genetics
Macrophage-1 Antigen - metabolism
Macrophages - drug effects
Macrophages - metabolism
Macrophages - pathology
Mice, Inbred C57BL -
Mice, Knockout -
Obesity - genetics
Obesity - metabolism
Obesity - pathology
Phenotype -
Signal Transduction - drug effects
Weight Gain -

Find related publications in this database (Keywords)
Obesity
metabolic disorders
inflammation
macrophage
adhesion molecules
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