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Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone(More)
Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we(More)
The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to(More)
Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and(More)
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells (APCs) isolated from visceral and(More)
Obesity represents a major risk factor for the development of several of our most common medical conditions, including Type 2 diabetes, dyslipidaemia, non-alcoholic fatty liver, cardiovascular disease and even some cancers. Although increased fat mass is the main feature of obesity, not all fat depots are created equal. Adipocytes found in white adipose(More)
Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing beta cells. We have disrupted expression of the mitochondrial protein frataxin selectively in pancreatic beta cells. Mice were born healthy but subsequently developed impaired glucose tolerance progressing to overt diabetes mellitus. These observations were(More)
Maintenance of body temperature is essential for the survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation. Owing to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans, BAT holds great promise for the treatment of obesity and metabolic syndrome.(More)
Body weight is regulated by coordinating energy intake and energy expenditure. Transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling has been shown to regulate energy balance in lower organisms, but whether a similar pathway exists in mammals is unknown. We have previously demonstrated that BMP7 can regulate brown adipogenesis and(More)
More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich(More)