Boutant 2015 Mol Metab

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Boutant M, Joffraud M, Kulkarni SS, Garcia-Casarrubios E, Garcia-Roves PM, Ratajczak J, Fernandez-Marcos PJ, Valverde AM, Serrano M, Canto C (2015) SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function. Mol Metab 4:118-31.

» PMID: 25685699 Open access

Boutant M, Joffraud M, Kulkarni SS, Garcia-Casarrubios E, Garcia-Roves PM, Ratajczak J, Fernandez-Marcos PJ, Valverde AM, Serrano M, Canto C (2015) Mol Metab

Abstract: OBJECTIVE: SIRT1 has been proposed to be a key signaling node linking changes in energy metabolism to transcriptional adaptations. Although SIRT1 overexpression is protective against diverse metabolic complications, especially in response to high-fat diets, studies aiming to understand the etiology of such benefits are scarce. Here, we aimed to identify the key tissues and mechanisms implicated in the beneficial effects of SIRT1 on glucose homeostasis.

METHODS: We have used a mouse model of moderate SIRT1 overexpression, under the control of its natural promoter, to evaluate glucose homeostasis and thoroughly characterize how different tissues could influence insulin sensitivity.

RESULTS: Mice with moderate overexpression of SIRT1 exhibit better glucose tolerance and insulin sensitivity even on a low fat diet. Euglycemic-hyperinsulinemic clamps and in-depth tissue analyses revealed that enhanced insulin sensitivity was achieved through a higher brown adipose tissue activity and was fully reversed by housing the mice at thermoneutrality. SIRT1 did not influence brown adipocyte differentiation, but dramatically enhanced the metabolic transcriptional responses to β3-adrenergic stimuli in differentiated adipocytes.

CONCLUSIONS: Our work demonstrates that SIRT1 improves glucose homeostasis by enhancing BAT function. This is not consequent to an alteration in the brown adipocyte differentiation process, but as a result of potentiating the response to β3-adrenergic stimuli.

Keywords: Brown adipose tissue, Energy homeostasis, Insulin resistance, SIRT1

O2k-Network Lab: CH Lausanne Canto C, ES Barcelona Garcia-Roves PM


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Skeletal muscle, Liver, Fat  Preparation: Permeabilized tissue, Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k