PMID- 19435851
OWN - NLM
STAT- MEDLINE
DCOM- 20090810
LR  - 20211020
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 297
IP  - 1
DP  - 2009 Jul
TI  - Central role of ceramide biosynthesis in body weight regulation, energy 
      metabolism, and the metabolic syndrome.
PG  - E211-24
LID - 10.1152/ajpendo.91014.2008 [doi]
AB  - Although obesity is associated with multiple features of the metabolic syndrome 
      (insulin resistance, leptin resistance, hepatic steatosis, chronic inflammation, 
      etc.), the molecular changes that promote these conditions are not completely 
      understood. Here, we tested the hypothesis that elevated ceramide biosynthesis 
      contributes to the pathogenesis of obesity and the metabolic syndrome. Chronic 
      treatment for 8 wk of genetically obese (ob/ob), and, high-fat diet-induced obese 
      (DIO) mice with myriocin, an inhibitor of de novo ceramide synthesis, decreased 
      circulating ceramides. Decreased ceramide was associated with reduced weight, 
      enhanced metabolism and energy expenditure, decreased hepatic steatosis, and 
      improved glucose hemostasis via enhancement of insulin signaling in the liver and 
      muscle. Inhibition of de novo ceramide biosynthesis decreased adipose expression 
      of suppressor of cytokine signaling-3 (SOCS-3) and induced adipose uncoupling 
      protein-3 (UCP3). Moreover, ceramide directly induced SOCS-3 and inhibited UCP3 
      mRNA in cultured adipocytes suggesting a direct role for ceramide in regulation 
      of metabolism and energy expenditure. Inhibition of de novo ceramide synthesis 
      had no effect on adipose tumor necrosis factor-alpha (TNF-alpha) expression but 
      dramatically reduced adipose plasminogen activator inhibitor-1 (PAI-1) and 
      monocyte chemoattactant protein-1 (MCP-1). This study highlights a novel role for 
      ceramide biosynthesis in body weight regulation, energy expenditure, and the 
      metabolic syndrome.
FAU - Yang, Guang
AU  - Yang G
AD  - Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San 
      Diego, CA 92121, USA.
FAU - Badeanlou, Leylla
AU  - Badeanlou L
FAU - Bielawski, Jacek
AU  - Bielawski J
FAU - Roberts, Amanda J
AU  - Roberts AJ
FAU - Hannun, Yusuf A
AU  - Hannun YA
FAU - Samad, Fahumiya
AU  - Samad F
LA  - eng
GR  - R01-HL-071146/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090512
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Ceramides)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Ion Channels)
RN  - 0 (Lysophospholipids)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Sphingolipids)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Ucp3 protein, mouse)
RN  - 0 (Uncoupling Protein 3)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - NGZ37HRE42 (Sphingosine)
RN  - YRM4E8R9ST (thermozymocidin)
SB  - IM
MH  - Adipose Tissue/pathology
MH  - Animals
MH  - Body Weight/*physiology
MH  - Ceramides/*biosynthesis/blood/physiology
MH  - Energy Metabolism/*physiology
MH  - Fatty Acids, Monounsaturated/pharmacology
MH  - Ion Channels/metabolism
MH  - Lysophospholipids/blood
MH  - Male
MH  - Metabolic Syndrome/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondrial Proteins/metabolism
MH  - Obesity/metabolism/pathology
MH  - Organ Size/physiology
MH  - Sphingolipids/metabolism
MH  - Sphingosine/analogs & derivatives/blood/metabolism
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/metabolism
MH  - Uncoupling Protein 3
PMC - PMC2711669
EDAT- 2009/05/14 09:00
MHDA- 2009/08/11 09:00
PMCR- 2010/07/01
CRDT- 2009/05/14 09:00
PHST- 2009/05/14 09:00 [entrez]
PHST- 2009/05/14 09:00 [pubmed]
PHST- 2009/08/11 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 91014.2008 [pii]
AID - E-91014-2008 [pii]
AID - 10.1152/ajpendo.91014.2008 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E211-24. doi: 
      10.1152/ajpendo.91014.2008. Epub 2009 May 12.