Abstract
BackgroundRecent data from this laboratory suggest that components of dairy foods may serve as activators of SIRT1 (Silent Information Regulator Transcript 1), and thereby participate in regulation of glucose and lipid metabolism. In this study, an ex-vivo/in-vitro approach was used to examine the integrated effects of dairy diets on SIRT1 activation in two key target tissues (adipose and muscle tissue).MethodsSerum from overweight and obese subjects fed low or high dairy diets for 28 days was added to culture medium (similar to conditioned media) to treat cultured adipocytes and muscle cells for 48 hours.ResultsTreatment with high dairy group conditioned media resulted in 40% increased SIRT1 gene expression in both tissues (p < 0.01) and 13% increased enzyme activity in adipose tissue compared to baseline. This was associated with increased gene expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF1), cytochrome oxidase c subunit 7 (Cox 7), NADH dehydrogenase and uncoupling protein 2 (UCP2) in adipocytes as well as uncoupling protein 3 (UCP3), NRF1 and Cox 7 in muscle cells (p < 0.05). Further, direct incubation of physiological concentrations of leucine and its metabolites α-Ketoisocaproic acid (KIC) and β-hydroxy-methylbuteric acid (HMB) with recombinant human SIRT1 enzyme resulted in 30 to 50% increase of SIRT1 activity (p < 0.05).ConclusionsThese data indicate that dairy consumption leads to systemic effects, which may promote mitochondrial biogenesis in key target tissues such as muscle and adipose tissue both by direct activation of SIRT1 as well as by SIRT1-independent pathways.
Highlights
Recent data from this laboratory suggest that components of dairy foods may serve as activators of SIRT1 (Silent Information Regulator Transcript 1), and thereby participate in regulation of glucose and lipid metabolism
Consistent with reports of SIRT1 effects on lifespan, dairy-rich diets reduced the early mortality in mice [15]. These observations provided the mechanistic framework for our hypothesis that calcitriol and leucine modulation of SIRT1 in adipose tissue and skeletal muscle is the central signaling event that links the effects of calcitriol, leucine and dairy foods on fatty acid oxidation, oxidative stress, insulin sensitivity and inflammatory stress
Dairy feeding resulted in 43% increase of SIRT1 gene expression in the muscle cells (p < 0.05), which was significantly different from baseline and soy-based control (Figure 5b)
Summary
Recent data from this laboratory suggest that components of dairy foods may serve as activators of SIRT1 (Silent Information Regulator Transcript 1), and thereby participate in regulation of glucose and lipid metabolism. The beneficial effects of energy restriction on lifespan and protection against metabolic disease are mediated, in part, by SIRT1 (Silent Information Regulator Transcript 1) and SIRT3 in mammals and by the SIRT1 orthologue Sir in lower species [1]. Dairy foods have been reported to have multiple effects on adipocyte and muscle metabolism and play a significant role in modulating energy metabolism and obesity risk [7,8,9] While some of these effects appear to be mediated by dietary calcium [10], recent evidence indicates that the high concentration of branched chain amino acids (BCAA) contribute to these effects. The BCAA leucine plays a distinct role as it has a pivotal function in protein synthesis signaling and as it appears to play an important role in the re-partitioning of dietary energy from adipose to skeletal muscle [11], it is not clear whether these effects are mediated by intact leucine or by its’ metabolites a-ketoisocaproate (KIC) and b-Hydroxy-b-Methylbutyrate (HMB)
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