PMID- 25700562
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20181113
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Linking)
VI  - 50
IP  - 1
DP  - 2015 Sep
TI  - Preservation of high-fat diet-induced femoral trabecular bone loss through 
      genetic target of TNF-alpha.
PG  - 239-49
LID - 10.1007/s12020-015-0554-5 [doi]
AB  - Obesity and osteoporosis are two common chronic diseases, however, the basis for 
      the correlation between them remains largely unknown. The pro-inflammation 
      cytokine tumor necrosis factor-alpha (TNF-alpha) plays important roles in lipid and 
      bone metabolisms, which may be a good candidate in the correlation between 
      obesity and osteoporosis. We investigated the pathological roles of TNF-alpha in 
      high-fat diet (HFD)-induced bone loss. Wild-type (WT) mice and TNF-alpha knockout 
      (TNF-alpha(-/-)) mice were fed with the standard diet or the HFD for 12 weeks. Bone 
      marrow stromal cells (BMSCs) from both genotypes were induced to differentiate 
      into osteoblasts and treated with palmitic acid (PA). Bone mass and 
      microstructure of femurs were evaluated by micro-CT. Lipid and bone metabolisms 
      were investigated by histological and plasma analyses, and real-time PCR. On the 
      HFD, both TNF-alpha(-/-) and WT mice presented notable visceral obesity, 
      dyslipidemia. Adipogenesis and osteoclastogenesis were enhanced, while 
      osteoblastogenesis was reduced in both genotypes. However, the changes were 
      significantly different between TNF-alpha(-/-) and WT mice after the HFD. The gain of 
      body and fat-pad weight was less and adipocyte area was smaller by 22 % in 
      TNF-alpha(-/-) mice. Osteoclast numbers and plasma CTX level were lower by 40 % and 
      by 23 % in TNF-alpha(-/-) mice. There were more ALP positive cells in the PA-treated 
      TNF-alpha(-/-) BMSCs. mRNA expression of PPAR-gamma was lower while that of Runx2 was 
      higher in the bone from TNF-alpha(-/-) HFD group and in the PA-treated TNF-alpha(-/-) 
      BMSCs, compared to WT on the same treatment. Furthermore, femoral trabecular bone 
      mass and trabecular bone number were significantly decreased in WT mice on the 
      HFD, whereas they were increased by 1.56-fold and 1.53-fold, respectively, in 
      TNF-alpha(-/-) mice on the same diet (P < 0.05). Our results demonstrated that TNF-alpha 
      gene knockout retained HFD-induced femoral trabecular bone loss mainly by 
      suppressing adipogenesis and osteoclastogenesis, and enhancing 
      osteoblastogenesis, which suggests that TNF-alpha plays a critical role in the 
      development of HFD-related bone metabolic disorders and it may be a new potential 
      therapeutic target for obesity-related bone loss.
FAU - Zhang, Kun
AU  - Zhang K
AD  - Laboratory of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, 
      West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, 
      Sichuan, People's Republic of China.
FAU - Wang, Chunyu
AU  - Wang C
FAU - Chen, Yaxi
AU  - Chen Y
FAU - Ji, Xiao
AU  - Ji X
FAU - Chen, Xiang
AU  - Chen X
FAU - Tian, Li
AU  - Tian L
FAU - Yu, Xijie
AU  - Yu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150221
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - 0 (Dietary Fats)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Adipose Tissue/*metabolism
MH  - Animals
MH  - Body Weight
MH  - Dietary Fats/*adverse effects
MH  - Femur/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Obesity/*metabolism
MH  - Osteoblasts/metabolism
MH  - Osteoclasts/metabolism
MH  - Osteoporosis/chemically induced/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 2015/02/24 06:00
MHDA- 2016/06/21 06:00
CRDT- 2015/02/22 06:00
PHST- 2014/11/05 00:00 [received]
PHST- 2015/02/13 00:00 [accepted]
PHST- 2015/02/22 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
AID - 10.1007/s12020-015-0554-5 [doi]
PST - ppublish
SO  - Endocrine. 2015 Sep;50(1):239-49. doi: 10.1007/s12020-015-0554-5. Epub 2015 Feb 
      21.