Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energy‐restricted aP2‐agouti transgenic mice

We have demonstrated previously a regulatory role for intracellular Ca 2+ ([Ca 2+ ] i ) in adipocyte lipogenesis and lipolysis and have recently reported that 1,25‐(OH) 2 ‐D increases adipocyte [Ca 2+ ]i, which causes increased lipogenesis and decreased lipolysis. We have now tested the hypothesis that suppressing 1,25‐(OH)2‐D by increasing dietary calcium will suppress adipocyte [Ca 2+ ] i , thereby facilitating weight loss by stimulating lipolysis and inhibiting lipogenesis in calorically (Kcal)‐restricted (70% of ad lib) aP2‐agouti transgenic (aP2‐a) mice. Mice (aP2‐a) exhibiting a pattern of obesity gene expression similar to humans were fed a low‐Ca (0.4%)/high‐fat/high‐sucrose diet for six weeks, resulting in a 27% and twofold increase in body weight and total fat pad mass, respectively, with a twofold increase in adipocyte [Ca 2+ ] i (p<0.001). Mice were then either maintained on the same low‐Ca basal diet ad lib or Kcal‐restricted (70% of ad lib) on this diet either unsupplemented (basal) or with 25% or 50% of the protein replaced by non‐fat dry milk (medium or high) dairy or supplemented with CaCO 3 to 1.2% Ca for six weeks. Adipocyte [Ca 2+ ] i was unaffected by Kcal restriction but was reduced markedly by all three high Ca diets (290 vs. 130 nM, p<0.001). Body weight was reduced by 11%, 19%, 25%, and 29% by the restricted basal, high‐Ca, medium‐dairy and high‐dairy diets, with corresponding decreases in fat pad mass of 8, 42, 60, and 69% vs. ad lib basal (p<0.001), respectively. The high‐Ca diets caused similar decreases in fatty acid synthase activity 35%‐63%, p<0.001), increases in lipolysis (two‐ to threefold, p<0.001). All three high‐Ca diets increased adipocyte uncoupling protein 2 expression approximately twofold (p<0.02), with a corresponding increase in core temperature (0.48‐0.67°C, p<0.05). Thus, high‐Ca diets suppress adipocyte [Ca 2+ ] i and thereby reduce energy storage and increase thermogenesis during Kcal restriction.