PMID- 14693700
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20190516
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 53
IP  - 1
DP  - 2004 Jan
TI  - Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is 
      glucose dependent: implications for long-term regulation of lipolysis.
PG  - 74-81
AB  - Tumor necrosis factor-alpha (TNF-alpha) and hyperglycemia both impair insulin 
      sensitivity in vivo. This may be secondary to stimulation of adipose tissue 
      lipolysis and consequent increased circulating free fatty acids (FFAs). Here we 
      report that neither TNF-alpha nor glucose alone has a pronounced effect on 
      lipolysis in 3T3-L1 adipocytes. However, the combination of TNF-alpha plus 
      glucose markedly stimulates lipolysis. Glucose does not affect the ability of 
      isoproterenol to stimulate lipolysis. Alternative substrates such as acetate, 
      pyruvate, and lactate do not allow the TNF-alpha effect. Mannose was almost as 
      effective as glucose; fructose was marginally effective, but galactose was 
      ineffective. The effectiveness of the sugars corresponded with production of 
      lactate, i.e., the cells readily produced lactate from glucose or mannose, 
      slightly from fructose, and not at all from galactose. The ability of TNF-alpha 
      to phosphorylate extracellular signal-regulated kinase 1 (ERK1) and ERK2 and to 
      downregulate perilipin (which has been implicated in the lipolytic effect of 
      TNF-alpha) was not affected by glucose. We conclude that the lipolytic action of 
      TNF-alpha is influenced by glucose in 3T3-L1 adipocytes. The findings suggest 
      that glucose metabolism is required for the lipolytic response to TNF-alpha but 
      not for early signaling events. These findings suggest novel mechanisms by which 
      TNF-alpha and hyperglycemia raise FFA levels and induce insulin resistance.
FAU - Green, Allan
AU  - Green A
AD  - Bassett Research Institute, Bassett Healthcare, Cooperstown, New York 13326, USA. 
      allan.green@basett.org
FAU - Rumberger, John M
AU  - Rumberger JM
FAU - Stuart, Charles A
AU  - Stuart CA
FAU - Ruhoff, Mary S
AU  - Ruhoff MS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Acetates)
RN  - 0 (Carrier Proteins)
RN  - 0 (Lactates)
RN  - 0 (Perilipin-1)
RN  - 0 (Phosphoproteins)
RN  - 0 (Pyruvates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3 Cells
MH  - Acetates/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Carrier Proteins
MH  - Glucose/metabolism/*pharmacology
MH  - Homeostasis/drug effects/physiology
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Lactates/metabolism
MH  - Lipolysis/*drug effects
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Perilipin-1
MH  - Phosphoproteins/drug effects/metabolism
MH  - Phosphorylation
MH  - Pyruvates/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2003/12/25 05:00
MHDA- 2004/02/28 05:00
CRDT- 2003/12/25 05:00
PHST- 2003/12/25 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2003/12/25 05:00 [entrez]
AID - 10.2337/diabetes.53.1.74 [doi]
PST - ppublish
SO  - Diabetes. 2004 Jan;53(1):74-81. doi: 10.2337/diabetes.53.1.74.