The brown fat specific UnCoupling Protein 1 (UCP1) is involved in thermogenesis, a process by which energy is dissipated as heat in response to cold stress and excess of caloric intake. Thermogenesis has potential implications for body mass control and cellular fat metabolism. In fact, in humans, the variability of the UCP1 gene is associated with obesity, fat gain and metabolism. Since regulation of metabolism is one of the key-pathways in lifespan extension, we tested the possible effects of UCP1 variability on survival.
White adipose tissue now emerges as a pivotal organ controlling lifespan. Calorie restriction, which so far extends lifespan in all organisms, primarily affects energy stores in adipose tissue. Genetic manipulations aiming at modifying fat mass also impact on the duration of life in several model organisms. We recently proposed that silent information regulator 2 (SIR2) ortholog, sirtuin 1 (SIRT1), the mammalian ortholog of the life-extending yeast gene SIR2, is involved in the molecular mechanisms linking lifespan to adipose tissue.
Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1-/- mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1-/- mice maintained in a room at 23 degrees C.
Members of the sirtuin family of NAD(+)-dependent protein deacetylases are important regulators of longevity in yeast, worms, and flies. Mammals have seven sirtuins (SIRT1-7), each characterized by differences in subcellular localization, substrate preference, and biological function. While it is unclear whether sirtuins regulate aging in mammals, it is clear that sirtuins influence diverse aspects of their metabolism. Indeed, SIRT1 promotes oxidation of fatty acids in liver and skeletal muscle, cholesterol metabolism in liver, and lipid mobilization in white adipose tissue.
Caloric restriction (CR) causes a reduction in body temperature (T(b)) which is suggested to contribute to changes that increase lifespan. Moreover, low T(b) has been shown to improve health and longevity independent of CR. In this review we examine the connections between CR, T(b) and mechanisms that influence longevity and ageing.
In virtually all organisms, life expectancy is profoundly affected by caloric intake. For example, dietary restriction (DR; a feeding regimen of fewer calories compared to the ad libitum level without causing malnutrition) has been shown to lengthen, whereas hypercaloric (HC) diet feeding to shorten, lifespan. Recent findings in invertebrates indicate that specialized groups of cells (e.g.: metabolic-sensing neurons) detect changes in caloric intake and convey energy-status-variation signals to other cells in the body to regulate lifespan.
Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months.
OBJECTIVE: We examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet. RESEARCH DESIGN AND METHODS: In dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber.
Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and adiposity and is a drug target for the treatment of obesity and diabetes. Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B substrate in adipocytes. PTP1B deficiency leads to increased PKM2 total tyrosine and Tyr(105) phosphorylation in cultured adipocytes and in vivo. Substrate trapping and mutagenesis studies identify PKM2 Tyr-105 and Tyr-148 as key sites that mediate PTP1B-PKM2 interaction.
We studied the effects of a 3-day fast and 20 days of refeeding on lipoprotein lipase activity (LPL) in the interscapular brown adipose tissue (BAT) of sexually mature male rats. Rats were refed either ad libitum or restricted quantities (75 or 50% of normal ad libitum food intake). BAT-LPL, expressed on a per depot basis, decreased with fasting and returned to control values by day 3 of refeeding ad libitum. In contrast, refeeding restricted quantities for 5 to 20 days limited regain of body weight and increased BAT-LPL significantly above the values observed in rats refed ad libitum.