Leucine and calcium regulate fat metabolism and energy partitioning in murine adipocytes and muscle cells

Dietary calcium modulation of adiposity is mediated, in part, by suppression of calcitriol, while the additional effect of dairy products is mediated by additional components; these include the high concentration of leucine, a key factor in the regulation of muscle protein turnover. We investigated the effect of leucine, calcitriol and calcium on energy metabolism in murine adipocytes and muscle cells and on energy partitioning between adipocytes and skeletal muscle. Leucine induced a marked increase in fatty acid oxidation in C2C12 muscle cells (P < 0.001) and decreased FAS expression by 66% (P < 0.001) in 3T3L1 adipocytes. Calcitriol decreased muscle cell fatty acid oxidation by 37% (P < 0.001) and increased adipocyte FAS gene expression by threefold (P < 0.05); these effects were partially reversed by either leucine or calcium channel antagonism with nifedipine. Coculture of muscle cells with adipocytes or incubation with 48-h adipocyte conditioned medium decreased muscle fatty acid oxidation by 62% (P < 0.001), but treating adipocytes with leucine and/or nifedipine attenuated this effect. Leucine, nifedipine and calcitriol also modulated adiponectin production and thereby exerted additional indirect effects on fatty acid oxidation in C2C12 myotubes. Adiponectin increased IL-15 and IL-6 release by myotubes and partially reversed the inhibitory effects of calcitriol. Comparable effects of leucine, calcitriol and adiponectin were found in myotubes treated with conditioned medium derived from adipocytes or co-cultured with adipocytes. These data suggest that leucine and nifedipine promote energy partitioning from adipocytes to muscle cells, resulting in decreased energy storage in adipocytes and increasing fatty acid utilization in muscle.