SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance

Giorgio Ramadori, Teppei Fujikawa, Jason Anderson, Eric D. Berglund, Renata Frazao, Shaday Michán, Claudia R. Vianna, David A. Sinclair, Carol F. Elias, Roberto Coppari

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

Original languageEnglish (US)
Pages (from-to)301-312
Number of pages12
JournalCell Metabolism
Volume14
Issue number3
DOIs
StatePublished - Sep 7 2011

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Steroidogenic Factor 1
Insulin Resistance
Obesity
Diet
Neurons
Type 2 Diabetes Mellitus
Energy Metabolism
Skeletal Muscle
Leptin
Neuropeptides
Hormones

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Ramadori, G., Fujikawa, T., Anderson, J., Berglund, E. D., Frazao, R., Michán, S., ... Coppari, R. (2011). SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metabolism, 14(3), 301-312. https://doi.org/10.1016/j.cmet.2011.06.014

SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. / Ramadori, Giorgio; Fujikawa, Teppei; Anderson, Jason; Berglund, Eric D.; Frazao, Renata; Michán, Shaday; Vianna, Claudia R.; Sinclair, David A.; Elias, Carol F.; Coppari, Roberto.

In: Cell Metabolism, Vol. 14, No. 3, 07.09.2011, p. 301-312.

Research output: Contribution to journalArticle

Ramadori, G, Fujikawa, T, Anderson, J, Berglund, ED, Frazao, R, Michán, S, Vianna, CR, Sinclair, DA, Elias, CF & Coppari, R 2011, 'SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance', Cell Metabolism, vol. 14, no. 3, pp. 301-312. https://doi.org/10.1016/j.cmet.2011.06.014
Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michán S et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metabolism. 2011 Sep 7;14(3):301-312. https://doi.org/10.1016/j.cmet.2011.06.014
Ramadori, Giorgio ; Fujikawa, Teppei ; Anderson, Jason ; Berglund, Eric D. ; Frazao, Renata ; Michán, Shaday ; Vianna, Claudia R. ; Sinclair, David A. ; Elias, Carol F. ; Coppari, Roberto. / SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. In: Cell Metabolism. 2011 ; Vol. 14, No. 3. pp. 301-312.
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