PMID- 21850461
OWN - NLM
STAT- MEDLINE
DCOM- 20120615
LR  - 20211020
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 359
IP  - 1-2
DP  - 2012 Jan
TI  - High-fat diet-induced obesity and insulin resistance were ameliorated via 
      enhanced fecal bile acid excretion in tumor necrosis factor-alpha receptor 
      knockout mice.
PG  - 161-7
LID - 10.1007/s11010-011-1010-3 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of the main mediators of inflammatory 
      response activated by fatty acids in obesity, and this signaling through TNF-alpha 
      receptor (TNFR) is responsible for obesity-associated insulin resistance. 
      Recently, TNF-alpha 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-alpha 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-alpha receptor 2 via increasing fecal bile acid and 
      lipid content excretion. Therefore, TNF-alpha signaling through TNFR2 is essentially 
      involved in the bile acid synthesis and excretion of lipids, resulting in its 
      beneficial effects.
FAU - Yamato, Mayumi
AU  - Yamato M
AD  - Department REDOX Medicinal Science, Faculty of Pharmaceutical Sciences, Kyushu 
      University, Fukuoka, 812-8582, Japan. yamato68@redoxnavi.med.kyushu-u.ac.jp
FAU - Shiba, Takeshi
AU  - Shiba T
FAU - Ide, Tomomi
AU  - Ide T
FAU - Seri, Naoko
AU  - Seri N
FAU - Kudo, Wataru
AU  - Kudo W
FAU - Ando, Makoto
AU  - Ando M
FAU - Yamada, Ken-ichi
AU  - Yamada K
FAU - Kinugawa, Shintaro
AU  - Kinugawa S
FAU - Tsutsui, Hiroyuki
AU  - Tsutsui H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110818
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Lipids)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Bile Acids and Salts/metabolism/*physiology
MH  - *Diet, High-Fat
MH  - Feces/chemistry
MH  - *Insulin Resistance
MH  - Lipid Metabolism
MH  - Lipids/biosynthesis
MH  - Mice
MH  - Mice, Knockout
MH  - *Obesity
MH  - Receptors, Tumor Necrosis Factor, Type II/*deficiency
MH  - Tumor Necrosis Factor-alpha
EDAT- 2011/08/19 06:00
MHDA- 2012/06/16 06:00
CRDT- 2011/08/19 06:00
PHST- 2011/05/24 00:00 [received]
PHST- 2011/07/27 00:00 [accepted]
PHST- 2011/08/19 06:00 [entrez]
PHST- 2011/08/19 06:00 [pubmed]
PHST- 2012/06/16 06:00 [medline]
AID - 10.1007/s11010-011-1010-3 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2012 Jan;359(1-2):161-7. doi: 10.1007/s11010-011-1010-3. Epub 
      2011 Aug 18.