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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalMolecular and cellular biochemistry
Volume359
Issue number1-2
DOIs
Publication statusPublished - Jan 1 2012

Fingerprint

Tumor Necrosis Factor Receptors
High Fat Diet
Nutrition
Bile Acids and Salts
Knockout Mice
Insulin Resistance
Tumor Necrosis Factor-alpha
Obesity
Fats
Insulin
Receptors, Tumor Necrosis Factor, Type II
Lipids
Cholesterol
Mixed Function Oxygenases
Lipase
Lipid Metabolism
Fatty Acids
Body Weight
Association reactions
Diet

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

High-fat diet-induced obesity and insulin resistance were ameliorated via enhanced fecal bile acid excretion in tumor necrosis factor-alpha receptor knockout mice. / Yamato, Mayumi; Shiba, Takeshi; Ide, Tomomi; Seri, Naoko; Kudo, Wataru; Ando, Makoto; Yamada, Ken Ichi; Kinugawa, Shintaro; Tsutsui, Hiroyuki.

In: Molecular and cellular biochemistry, Vol. 359, No. 1-2, 01.01.2012, p. 161-167.

Research output: Contribution to journalArticle

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AU - Kudo, Wataru

AU - Ando, Makoto

AU - Yamada, Ken Ichi

AU - Kinugawa, Shintaro

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