Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4 Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-Fed Mice
作者： Maziyar Saberi , Niels-Bjarne Woods , Carl de Luca , Simon Schenk , Juu Chin Lu
DOI: 10.1016/J.CMET.2009.09.006
关键词: TLR4 、 Glucose clamp technique 、 Adipose tissue 、 Adipose tissue macrophages 、 Hyperinsulinemia 、 Endocrinology 、 Fasting hyperinsulinemia 、 Biology 、 Internal medicine 、 Inflammation 、 Insulin resistance 、 Cell biology 、 Physiology 、 Molecular biology
摘要: Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) a key initiator inflammatory responses macrophages. We performed bone marrow transplantation (BMT) Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4(-/-)) and (BMT-WT) mice. After 16 weeks high-fat diet (HFD), BMT-WT developed obesity, hyperinsulinemia, glucose intolerance, In contrast, BMT-Tlr4(-/-) became obese but did not develop fasting hyperinsulinemia had improved hepatic sensitivity during euglycemic clamp studies, compared HFD controls. also showed markedly reduced tissue markers macrophage content. summary, our results indicate that signaling hematopoietic-derived for the development resistance
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