Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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
Doi: 10.1160/TH16-07-0553
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Anto Michel Nathaly
- Zirlik Andreas
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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