Impaired noradrenaline-induced lipolysis in white fat of aP2-Ucp1 transgenic mice is associated with changes in G-protein levels
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12023879
PubMed Central
PMC1222581
DOI
10.1042/bj20011438
PII: BJ20011438
Knihovny.cz E-resources
- MeSH
- Adenosine Diphosphate metabolism MeSH
- Adenosine Triphosphate metabolism MeSH
- Cyclic AMP metabolism MeSH
- DNA Primers MeSH
- Genotype MeSH
- Hepatocytes enzymology MeSH
- Ion Channels MeSH
- Lipase genetics MeSH
- Lipolysis * MeSH
- Membrane Proteins genetics physiology MeSH
- Mitochondrial Proteins MeSH
- Mice, Inbred C57BL MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Norepinephrine metabolism MeSH
- GTP-Binding Proteins metabolism MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Base Sequence MeSH
- Carrier Proteins genetics physiology MeSH
- Adipose Tissue enzymology metabolism MeSH
- Uncoupling Protein 1 MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine Diphosphate MeSH
- Adenosine Triphosphate MeSH
- Cyclic AMP MeSH
- DNA Primers MeSH
- Ion Channels MeSH
- Lipase MeSH
- Membrane Proteins MeSH
- Mitochondrial Proteins MeSH
- Norepinephrine MeSH
- GTP-Binding Proteins MeSH
- Carrier Proteins MeSH
- Ucp1 protein, mouse MeSH Browser
- Uncoupling Protein 1 MeSH
In vitro experiments suggest that stimulation of lipolysis by catecholamines in adipocytes depends on the energy status of these cells. We tested whether mitochondrial uncoupling proteins (UCPs) that control the efficiency of ATP production could affect lipolysis and noradrenaline signalling in white fat in vivo. The lipolytic effect of noradrenaline was lowered by ectopic UCP1 in white adipocytes of aP2-Ucp1 transgenic mice, overexpressing the UCP1 gene from the aP2 gene promoter, reflecting the magnitude of UCP1 expression, the impaired stimulation of cAMP levels by noradrenaline and the reduction of the ATP/ADP ratio in different fat depots. Thus only subcutaneous but not epididymal fat was affected. UCP1 also down-regulated the expression of hormone-sensitive lipase and lowered its activity, and altered the expression of trimeric G-proteins in adipocytes. The adipose tissue content of the stimulatory G-protein alpha subunit was increased while that of the inhibitory G-protein alpha subunits decreased in response to UCP1 expression. Our results support the idea that the energy status of cells, and the ATP/ADP ratio in particular, modulates the lipolytic effects of noradrenaline in adipose tissue in vivo. They also demonstrate changes at the G-protein level that tend to overcome the reduction of lipolysis when ATP level in adipocytes is low. Therefore, respiratory uncoupling may exert a broad effect on hormonal signalling in adipocytes.
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