Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-01-14

AUTHORS

Keitarou Kawasaki, Masanori Abe, Fujimasa Tada, Yoshio Tokumoto, Shiyi Chen, Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Yoichi Hiasa, Morikazu Onji

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. More... »

PAGES

311-321

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.2012.176

DOI

http://dx.doi.org/10.1038/labinvest.2012.176

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034991680

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23318884


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81 lipid metabolism
82 liver
83 metabolic syndrome
84 metabolism
85 mice
86 nonalcoholic steatohepatitis
87 number
88 obesity
89 patients
90 process
91 progression
92 protective role
93 resistance
94 role
95 sensitivity
96 serum IgG
97 serum levels
98 signaling
99 steatohepatitis
100 steatosis
101 syndrome
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