Understanding the role of the Histone Deacetylase SIRT6 in brown adipose tissue

CLAUDIA COSENTINO; S SEREDA; LIESA M; D.M. SILBERMAN; SHIRIHAI O; ETCHEGARAY JP; CHOI J; CARLOS SEBASTIÁN; LEI ZHONG; DEBORAH TOIBER; KUGEL S; RAUL MOSTOSLAVSKY

Keystone

Simposio; Adipose Tissue Biology Keystone Symposia; 2013

Being overweight or obese in childhood or adolescence increases the risk ofdeveloping type 2 diabetes and cardiovascular disease independent of adulthoodobesity, suggesting that excessive white adipose tissue (WAT) accumulation andaltered lipid pro les may be particularly harmful at speci c developmental points.The aim of this study is to characterize the cellular and molecular mechanismsinvolved in the establishment, maintenance and expansion of visceral andsubcutaneous WAT and their impact on glucose homeostasis and heart function.Methods: The timing and duration of high fat diet-induced obesity in maleC57BL/6J mice was modulated to induce adipocyte precursor proliferationand di erentiation in speci c depots in vivo, and assess the impact on bodycomposition, energy homeostasis and cardiovascular disease.Results: Exposure to obesogenic stimuli only during adolescence (postnatal day18 to P35) leads to increased fat mass that persists for 4-5 weeks after a switch toa low-fat control diet. Moreover, adolescent, but not adult, high-fat diet results inthe proliferation and di erentiation of adipocyte precursors in both subcutaneousand visceral WAT depots. Despite the recovery of fat mass to control levels there ispersistence of signi cant glucose intolerance and insulin resistance. Furthermore,reduced heart function, shown by signi cantly reduced ejection fraction, isobserved at 6 months of age in mice fed high-fat diet during adolescencecompared to obesity induced in adulthood and standard diet controls.Conclusions: This study indicates that short diet-induced obesogenic stimuliduring adolescence results in long-term changes in adipose tissue set point,glucose homeostasis and increased risk of cardiovascular disease.