title: Metformin Down-regulates TNF-α Secretion via Suppression of Scavenger Receptors in Macrophages.
abstract: Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) through down-regulation of NF-κB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-α and reduced the protein and mRNA expression of TNF-α in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-α and the expressions of scavenger receptors.
authors.affiliation: College of Pharmacy, Sahmyook University, Seoul 139-742, Korea.
authors.forename: Bobae
authors.initials: B
authors.lastname: Hyun
authors.forename: Seulmee
authors.initials: S
authors.lastname: Shin
authors.forename: Aeri
authors.initials: A
authors.lastname: Lee
authors.forename: Sungwon
authors.initials: S
authors.lastname: Lee
authors.forename: Youngcheon
authors.initials: Y
authors.lastname: Song
authors.forename: Nam-Joo
authors.initials: NJ
authors.lastname: Ha
authors.forename: Kyung-Hea
authors.initials: KH
authors.lastname: Cho
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Kim
keywords: Metformin; Obesity-induced inflammation; Scavenger receptors; TNF-α