Yu Ma1,2, Xinyue Liu1, Yaliu Wu3, Wendong Wang1, Xiaotong Chang4. 1. Key Laboratory of Clinical Diagnostics, Hebei North University, No 11, Zuanshi South Road, Zhangjiakou, 075000, Hebei, China. 2. Health Center of Xuxinzhuang, Tongzhou District, Beijing, 101121, China. 3. Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China. 4. Key Laboratory of Clinical Diagnostics, Hebei North University, No 11, Zuanshi South Road, Zhangjiakou, 075000, Hebei, China. changxt1212@vip.sina.com.
Abstract
BACKGROUND: Toll-like receptor 2 (TLR2) deficiency can increase insulin sensitivity and improves glucose tolerance. However, it is not yet fully understood about its underlying mechanism. The regulation of M1/M2 macrophage polarization has been verified to involve in insulin resistance. Here, we evaluated whether the beneficial effect of TLR2 deficiency is mediated by TLR2-associated macrophage polarization in mice fed with high-fat diet (HFD). METHODS AND RESULTS: Wild-type and TLR2 knockout (TLR2-/-) mice received HFD for two months. Following intraperitoneal glucose tolerance and insulin resistance tests, peripheral monocytes were isolated, and in vitro induced for differentiation into M1 and M2 macrophages, respectively. Macrophages polarization was evaluated using flow cytometry. The expression of macrophage polarization marker genes and cytokine production in visceral adipose tissue were measured by qRT-PCR and ELISA. Compared to wild-type mice, TLR2-/- mice showed higher glucose tolerance and insulin sensitivity, along with significantly reduced the population of M1 and increased M2 count in vitro. Additionally, TLR2-/- mice demonstrated higher expression of M2 marker iNOS mRNA and interleukin-10 level in adipose tissues. CONCLUSIONS: Our results reveal that TLR2 knockout-mediated macrophages M2 polarization is a crucial factor for preventing against diet-induced insulin resistance in mice. These findings deepen our knowledge about the mechanism underlying HFD-induced insulin resistance.
BACKGROUND: Toll-like receptor 2 (TLR2) deficiency can increase insulin sensitivity and improves glucose tolerance. However, it is not yet fully understood about its underlying mechanism. The regulation of M1/M2 macrophage polarization has been verified to involve in insulin resistance. Here, we evaluated whether the beneficial effect of TLR2 deficiency is mediated by TLR2-associated macrophage polarization in mice fed with high-fat diet (HFD). METHODS AND RESULTS: Wild-type and TLR2 knockout (TLR2-/-) mice received HFD for two months. Following intraperitoneal glucose tolerance and insulin resistance tests, peripheral monocytes were isolated, and in vitro induced for differentiation into M1 and M2 macrophages, respectively. Macrophages polarization was evaluated using flow cytometry. The expression of macrophage polarization marker genes and cytokine production in visceral adipose tissue were measured by qRT-PCR and ELISA. Compared to wild-type mice, TLR2-/- mice showed higher glucose tolerance and insulin sensitivity, along with significantly reduced the population of M1 and increased M2 count in vitro. Additionally, TLR2-/- mice demonstrated higher expression of M2 marker iNOS mRNA and interleukin-10 level in adipose tissues. CONCLUSIONS: Our results reveal that TLR2 knockout-mediated macrophages M2 polarization is a crucial factor for preventing against diet-induced insulin resistance in mice. These findings deepen our knowledge about the mechanism underlying HFD-induced insulin resistance.
Authors: J A Ehses; D T Meier; S Wueest; J Rytka; S Boller; P Y Wielinga; A Schraenen; K Lemaire; S Debray; L Van Lommel; J A Pospisilik; O Tschopp; S M Schultze; U Malipiero; H Esterbauer; H Ellingsgaard; S Rütti; F C Schuit; T A Lutz; M Böni-Schnetzler; D Konrad; Marc Y Donath Journal: Diabetologia Date: 2010-04-21 Impact factor: 10.122