High-fat diet-induced obesity and insulin resistance were ameliorated via enhanced fecal bile acid excretion in tumor necrosis factor-alpha receptor knockout mice

Mayumi Yamato, Takeshi Shiba, Tomomi Ide, Naoko Seri, Wataru Kudo, Makoto Ando, Ken Ichi Yamada, Shintaro Kinugawa, Hiroyuki Tsutsui

研究成果: ジャーナルへの寄稿記事

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Tumor necrosis factor-α (TNF-α) is one of the main mediators of inflammatory response activated by fatty acids in obesity, and this signaling through TNF-α receptor (TNFR) is responsible for obesity-associated insulin resistance. Recently, TNF-α has shown to affect lipid metabolism including the regulation of lipase activity and bile acid synthesis. However, there is scanty in vivo evidence for the involvement of TNF-α in this process, and the mechanistic role of TNFR remains unclear. In this study, TNFR2 knockout mice (R2KO) and wild-type (WT) mice were fed commercial normal diet (ND) or high-fat diet (HFD) for 8 weeks. In R2KO/HFD mice, the increase in body weight and the accumulation of fat were significantly ameliorated compared with WT/HFD mice in association with the decrease in plasma total cholesterol (137.7 ± 3.1 vs. 98.6 ± 3.1 mg/dL, P < 0.005), glucose (221.9 ± 14.7 vs. 167.3 ± 8.1 mg/dL, P < 0.01), and insulin (5.1 ± 0.3 vs. 3.4 ± 0.3 ng/mL, P < 0.05). Fecal excretion of lipid contents was significantly increased in R2KO mice. In R2KO/HFD mice, the decrease in hepatic cholesterol-7a-hydroxylase activity, the rate-limiting enzyme in bile acid synthesis, was inhibited (1.7 ± 0.2 vs. 8.1 ± 1.0 pmol/min/mg protein, P < 0.01). These results suggested that HFD-induced obesity with metabolic derangements could be ameliorated in mice lacking TNF-α receptor 2 via increasing fecal bile acid and lipid content excretion. Therefore, TNF-α signaling through TNFR2 is essentially involved in the bile acid synthesis and excretion of lipids, resulting in its beneficial effects.

元の言語英語
ページ(範囲)161-167
ページ数7
ジャーナルMolecular and cellular biochemistry
359
発行部数1-2
DOI
出版物ステータス出版済み - 1 1 2012

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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