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Neuronal modulation of brown adipose activity through perturbation of white adipocyte lipogenesis
A. Guilherme, DJ. Pedersen, F. Henriques, AH. Bedard, E. Henchey, M. Kelly, DA. Morgan, K. Rahmouni, MP. Czech,
Language English Country Germany
Document type Journal Article, Research Support, N.I.H., Extramural
Grant support
P01 HL084207
NHLBI NIH HHS - United States
R01 DK030898
NIDDK NIH HHS - United States
R01 DK103047
NIDDK NIH HHS - United States
R37 DK030898
NIDDK NIH HHS - United States
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- MeSH
- Adiposity MeSH
- Adipocytes, Beige metabolism MeSH
- Adipose Tissue, White metabolism MeSH
- Adipocytes, White metabolism MeSH
- Adipose Tissue, Brown metabolism MeSH
- Adipocytes, Brown metabolism MeSH
- Lipogenesis MeSH
- Mice MeSH
- Neurons metabolism MeSH
- Obesity metabolism MeSH
- Signal Transduction MeSH
- Fatty Acid Synthases MeSH
- Fatty Acid Synthase, Type I genetics metabolism MeSH
- Thermogenesis MeSH
- Body Temperature Regulation MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT). METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This increased sympathetic innervation could be observed at both 22 °C and 30 °C, indicating it is not a response to heat loss but rather adipocyte signaling. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. CONCLUSION: These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.
Department of Pharmacology University of Iowa Carver College of Medicine Iowa City IA 52242 USA
Program in Molecular Medicine University of Massachusetts Medical School Worcester MA 01605 USA
References provided by Crossref.org
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