PMID- 21750268
OWN - NLM
STAT- MEDLINE
DCOM- 20111118
LR  - 20211020
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 301
IP  - 4
DP  - 2011 Oct
TI  - Homocysteine suppresses lipolysis in adipocytes by activating the AMPK pathway.
PG  - E703-12
LID - 10.1152/ajpendo.00050.2011 [doi]
AB  - Hyperhomocysteinemia (HHcy) is an independent risk factor for coronary artery 
      disease. Emerging evidence suggests that HHcy is also associated with adipocyte 
      tissue dysfunction. One of the principal functions of adipose tissue is to 
      provide energy substrate via lipolysis. In the present study, we investigated the 
      effects of homocysteine (Hcy) on lipolysis in adipocytes. We found that Hcy 
      inhibited release of glycerol and fatty acids, two typical indicators of the 
      lipolytic response, in primary adipocytes and fully differentiated 3T3-L1 
      adipocytes in a dose-dependent manner under both basal and 
      isoproterenol-stimulated conditions. In differentiated 3T3-L1 adipocytes, 
      decreased glycerol and free fatty acid (FFA) release was associated with 
      elevation of intracellular TG content. Further studies showed that Hcy-mediated 
      antilipolytic responses were independent of the cyclic AMP-PKA and MEK-ERK1/2 
      pathways. However, Hcy increased phosphorylation levels of AMP-activated protein 
      kinase (AMPK) and its downstream enzyme acetyl-CoA carboxylase. Compound C, an 
      AMPK inhibitor, abolished Hcy-induced reduction of glycerol and FFA release under 
      both basal and isoproterenol-stimulated conditions. Furthermore, AMPKalpha1 siRNA 
      reversed Hcy-inhibited glycerol release. Supplementation of exogenous Hcy in the 
      diet for 2 wk lowered circulating glycerol and FFA levels. Moreover, Hcy 
      supplementation was associated with elevated leptin levels and reduced 
      adiponectin levels in plasma. These results show that Hcy inhibits lipolysis 
      through a pathway that involves AMPK activation.
FAU - Wang, Zhigang
AU  - Wang Z
AD  - Department of Kinesiology and Nutrition, University of Illinois at Chicago, USA.
FAU - Pini, Maria
AU  - Pini M
FAU - Yao, Tong
AU  - Yao T
FAU - Zhou, Zhanxiang
AU  - Zhou Z
FAU - Sun, Changhao
AU  - Sun C
FAU - Fantuzzi, Giamila
AU  - Fantuzzi G
FAU - Song, Zhenyuan
AU  - Song Z
LA  - eng
GR  - R01 DK083328/DK/NIDDK NIH HHS/United States
GR  - K01-AA-015344/AA/NIAAA NIH HHS/United States
GR  - R01-AA-017442/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110712
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Acetyl-CoA Carboxylase/metabolism
MH  - Adenylate Kinase/*metabolism
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Homocysteine/*metabolism/pharmacology
MH  - Lipolysis/drug effects/*physiology
MH  - Mice
MH  - Phosphorylation/physiology
MH  - Signal Transduction/drug effects/*physiology
PMC - PMC3191546
EDAT- 2011/07/14 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/01
CRDT- 2011/07/14 06:00
PHST- 2011/07/14 06:00 [entrez]
PHST- 2011/07/14 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - ajpendo.00050.2011 [pii]
AID - E-00050-2011 [pii]
AID - 10.1152/ajpendo.00050.2011 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2011 Oct;301(4):E703-12. doi: 
      10.1152/ajpendo.00050.2011. Epub 2011 Jul 12.