title: Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity.
abstract: Chronic inflammation is an important contributor to the development and progression of metabolic syndrome. Recent evidence indicates that, in addition to innate immune cells, adaptive immune cells have an important role in this process. We previously showed that the serum level of B-cell-activating factor (BAFF) was increased in patients with nonalcoholic steatohepatitis. However, it is currently unknown whether BAFF and BAFF-R (BAFF-R) have a role in lipid metabolism in the liver. To address this issue, the role played by BAFF and BAFF-R signaling in the development of insulin resistance and hepatic steatosis was examined in BAFF-R(-/-) mice fed a high-fat diet (HFD). Furthermore, the effect of BAFF on lipid metabolism in hepatocytes was analyzed in vitro. BAFF-R(-/-) mice showed improvements in HFD-induced obesity and insulin resistance. In addition, the number of B cells, levels of serum IgG, and inflammation of visceral fat were reduced in these mice. However, the expression of steatogenic genes and fatty acid deposition in the liver was higher in these mice than in control mice. BAFF was also found to downregulate the expression of steatogenesis genes and enhance steatosis in hepatocytes through BAFF-R. Collectively, these data indicated that, in addition to its known functions in inflammation and glucose metabolism, BAFF has a protective role in hepatic steatosis by regulating lipid metabolism in the liver.
authors: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Keitarou
authors: K
authors: Kawasaki
authors: Masanori
authors: M
authors: Abe
authors: Fujimasa
authors: F
authors: Tada
authors: Yoshio
authors: Y
authors: Tokumoto
authors: Shiyi
authors: S
authors: Chen
authors: Teruki
authors: T
authors: Miyake
authors: Shinya
authors: S
authors: Furukawa
authors: Bunzo
authors: B
authors: Matsuura
authors: Yoichi
authors: Y
authors: Hiasa
authors: Morikazu
authors: M
authors: Onji
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007074:Immunoglobulin G; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014280:Triglycerides; D002784:Cholesterol