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Xiao-Lu Tang, Chang-Nan Wang, Xiao-Yan Zhu, Xin Ni
Rosiglitazone (RSG) can cause bone loss, however the mechanisms remain largely unknown. This study aims to investigate the effects of RSG on differentiation and mineralization of osteoblasts using primary cultured mouse fetal calvaria-derived osteoblasts as a model, and elucidate the receptor and signaling pathways responsible for these effects. We found that RSG suppressed the differentiation and mineralization of calvaria-derived osteoblasts. Peroxisome proliferators-activated receptor γ (PPARγ) siRNA significantly reversed the inhibitory effect of RSG on osteogenic differentiation...
September 15, 2015: Molecular and Cellular Endocrinology
Fabien Wauquier, Claire Philippe, Laurent Léotoing, Sylvie Mercier, Marie-Jeanne Davicco, Patrice Lebecque, Jérôme Guicheux, Paul Pilet, Elisabeth Miot-Noirault, Vincent Poitout, Thierry Alquier, Véronique Coxam, Yohann Wittrant
The mechanisms linking fat intake to bone loss remain unclear. By demonstrating the expression of the free fatty acid receptor G-coupled protein receptor 40 (GPR40) in bone cells, we hypothesized that this receptor may play a role in mediating the effects of fatty acids on bone remodeling. Using micro-CT analysis, we showed that GPR40(-/-) mice exhibit osteoporotic features suggesting a positive role of GPR40 on bone density. In primary cultures of bone marrow, we showed that GW9508, a GRP40 agonist, abolished bone-resorbing cell differentiation...
March 1, 2013: Journal of Biological Chemistry
Jinwei Wu, Peng Sun, Xiaodong Zhang, Hong Liu, Hualiang Jiang, Weiliang Zhu, Heyao Wang
Chronic exposure to elevated concentration of free fatty acids (FFA) has been verified to induce endoplasmic reticulum (ER) stress, which leads to pancreatic β-cell apoptosis. As one of the medium and long chain FFA receptors, GPR40 is highly expressed in pancreatic β cells, mediates both acute and chronic effects of FFA on β-cell function, but the role of GPR40 in FFA-induced β-cell apoptosis remains unclear. In this study, we investigated the possible effects of GPR40 in palmitate-induced MIN6 β-cell apoptosis, and found that DC260126, a novel small molecular antagonist of GPR40, could protect MIN6 β cells from palmitate-induced ER stress and apoptosis...
April 2012: Journal of Cellular Biochemistry
Dexuan Ma, Bangbao Tao, Shogo Warashina, Susumu Kotani, Li Lu, Desislav B Kaplamadzhiev, Yoshimi Mori, Anton B Tonchev, Tetsumori Yamashima
The G-protein coupled receptor 40 (GRP40) is a transmembrane receptor for free fatty acids, and is known for its relation to insulin secretion in the pancreas. Recent studies demonstrated that spatial memory and hippocampal long-term potentiation of rodents and cognitive function of humans are improved by a dietary supplementation with arachidonic and/or docosahexaenoic acids, which are possible ligands for GPR40. While free fatty acid effects on the brain might be related to GPR40 activation, the role of GPR40 in the central nervous system (CNS) is at present not known...
August 2007: Neuroscience Research
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