title: Interleukin-6 gene knockout antagonizes high-fat-induced trabecular bone loss.
abstract: The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6(-/-)) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6(-/-) mice. The dysregulation of lipid metabolism was more serious in IL6(-/-) mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6(-/-) mice than those in WT mice on the HFD (P < 0.05). IL6(-/-) osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6(-/-) mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss.
authors: Chunyu
authors: C
authors: Wang
authors: Li
authors: L
authors: Tian
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Kun
authors: K
authors: Zhang
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Yaxi
authors: Y
authors: Chen
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Xiang
authors: X
authors: Chen
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Ying
authors: Y
authors: Xie
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: Qian
authors: Q
authors: Zhao
authors: Laboratory of Endocrinology and MetabolismDepartment of Endocrinology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China xijieyu@hotmail.com xijieyu@scu.edu.cn.
authors: Xijie
authors: X
authors: Yu
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics* / Q000473:pathology*; D000071556:Cancellous Bone / Q000378:metabolism* / Q000473:pathology*; D059305:Diet, High-Fat; D055786:Gene Knockout Techniques; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics
chemical_list: D015850:Interleukin-6; D008055:Lipids
keywords: adipocyte; bone metabolism; interleukin-6; lipid metabolism; osteoblasts; osteoclasts