Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes
Lee, YS; Park, MS; Choung, JS; Kim, SS; Oh, HH; Choi, CS; Ha, SY; Kang, Y; Kim, Y; Jun, HS
Diabetologia, 55(9):2456-2468, 2012
AIMS/HYPOTHESIS: Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
METHODS: We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an ob/ob mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
RESULTS: Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Macrophage populations (F4/80(+) and F4/80(+)CD11b(+)CD11c(+) cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated ob/ob mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
CONCLUSIONS/INTERPRETATION: We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.
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