Effects of dairy consumption on SIRT1 and metabolic risk in humans

The beneficial effects of energy restriction are mediated, in part, by SIRT1, and our recent data suggest that dairy components may activate SIRT1. Accordingly, we tested the hypothesis that dairy foods stimulate SIRT1 activity by using an ex vivo/in vitro approach to examine the integrated effects of dairy diets in two key target tissues (adipose and muscle). Serum from 20 overweight and obese subjects fed low or high dairy diets for 28 days was used to reflect the integrated systemic response to the diets and was then added to culture medium (similar to conditioned media) to treat cultured adipocytes and muscle cells for 48 hours. High, but not low, dairy serum caused a 40% increase in SIRT1 expression vs. baseline serum in both tissues (p<0.01) and a 30% increase in SIRT1 activity in adipocytes (p=0.05). This was associated with increased expression of adipocyte mitochondrial NADH dehydrogenase (MT‐ND1) and UCP2 (p<0.04) and muscle UCP3, NRF1 and COX7 (p<0.03). We then tested the potential of leucine and its metabolites α‐ketoisocaproic acid and β‐HMB acid to directly activate SIRT1, and found physiological concentrations of all three to stimulate 30 to 50% increases (p<0.005), while valine exerted no effect. These data demonstrate that dairy activates SIRT1 and key enzymes of mitochondrial biogenesis in key target tissues and may thereby protect against metabolic disease. Supported by the Dairy Research Institute.