Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women

Institute of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
International journal of obesity (2005) (Impact Factor: 5). 06/2008; 32(8):1250-5. DOI: 10.1038/ijo.2008.78
Source: PubMed


Calorie restriction increases the life span in a number of different organisms. This effect is dependent upon activation of the Sirt1 enzyme, and many of the beneficial effects of calorie restriction can be mimicked using resveratrol, which activates the Sirt1 enzyme. Nothing is known about this system in human adipose tissue; therefore, we investigated this system in human adipose tissue.
Sirt1 mRNA was measured in adipose tissue biopsies from human volunteers before and after 6 days of total fasting. In addition, adipose tissue from lean and obese individuals was compared and in vitro investigations were performed.
Long-term total fasting (6 days) of nine human volunteers increased Sirt1 mRNA expression in subcutaneous adipose tissue more than twofold (0.197-0.454 arbitrary units, P<0.05). Likewise, lean women (n=12) had more than twofold higher Sirt1 expression in subcutaneous adipose tissue compared to obese women (n=12; 0.33-0.73 arbitrary units, P<0.05). Sirt1 was equally expressed in the stroma-vascular fraction and the isolated adipocyte fraction. Finally, in vitro, we demonstrated that resveratrol (a Sirt1 activator) significantly enhanced the lipolytic effect of epinephrine in human adipose tissue (P<0.05).
Human adipose tissue contains Sirt1 and the expression of Sirt1 can be regulated by calorie restriction as in other species. Furthermore, we demonstrated that resveratrol affects human fat-cell metabolism similar to the effects in rodents (that is, increased epinephrine induced lipolysis). These findings indicated that the beneficial effects of calorie restriction in humans might involve the activation of Sirt1. Thus, based on these findings, we propose that Sirt1 might play important roles for the beneficial effects of calorie restriction in humans.

Download full-text


Available from: Bjørn Richelsen, Nov 19, 2014
  • Source
    • "Nevertheless, there appears to be a connection between fasting (as an inducer of autophagy), sirtuin activation, and fat metabolism. For instance, SIRT1 expression in human adipose tissue is decreased in obese women but restored upon fasting (Pedersen et al., 2008). The mitochondrial sirtuin paralog SIRT3 stimulates fasting-induced fatty acid oxidation in mice via deacetylation-mediated activation of long chain acyl-CoA dehydrogenase (LCAD) (Hirschey et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The phenomenon of aging is an intrinsic feature of life. Accordingly, the possibility to manipulate it has fascinated humans likely since time immemorial. Recent evidence is shaping a picture where low caloric regimes and exercise may improve healthy senescence, and several pharmacological strategies have been suggested to counteract aging. Surprisingly, the most effective interventions proposed to date converge on only a few cellular processes, in particular nutrient signaling, mitochondrial efficiency, proteostasis, and autophagy. Here, we critically examine drugs and behaviors to which life- or healthspan-extending properties have been ascribed and discuss the underlying molecular mechanisms.
    Cell 06/2014; 157(7):1515-1526. DOI:10.1016/j.cell.2014.05.031 · 32.24 Impact Factor
  • Source
    • "Treatment with pioglitazone, a PPARγ agonist, enhanced SIRT1 expression [60]. Similar attenuations in SIRT1 levels were reported in adipocytes from ob/ob mice [61] and adipose tissue from obese women [62]. SIRT1 gain-of-function studies in various models of insulin resistance and diabetes have revealed improved glucose tolerance and decreased energy expenditure that is due to lower hepatic glucose production and increased adiponectin levels [63] suggesting that SIRT1-mediated longevity may be related to improvements in insulin sensitivity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions.
    Experimental Diabetes Research 01/2012; 2012(11):642038. DOI:10.1155/2012/642038 · 4.33 Impact Factor
  • Source
    • "Circumstances that result in SIRT1 under-expression in adipose tissue enhanced adipogenesis, while circumstances that promote fat SIRT1 over-expression were characterized by attenuated adipogenesis and increased lipolysis [111]. Consistent with this idea, lean women had more than twofold higher SIRT1 expression compared to obese women [112]. Benefits of SIRT1 over-expression also included less inflammation, better glucose tolerance, and almost complete protection against hepatic steatosis, suggesting that SIRT1 plays an important role in obesity-associated metabolic adverse effects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered.
    Journal of Translational Medicine 11/2011; 9(1):202. DOI:10.1186/1479-5876-9-202 · 3.93 Impact Factor
Show more