Regulation of adiposity by dietary calcium

Abstract

Recent data from this laboratory demonstrate that increasing adipocyte intracellular Ca(2+) results in a coordinated stimulation of lipogenesis and inhibition of lipolysis. We have also noted that increasing dietary calcium of obese patients for 1 year resulted in a 4.9 kg loss of body fat (P<0.01). Accordingly, we tested the possibility that calcitrophic hormones may act on adipocytes to increase Ca(2+) and lipid metabolism by measuring the effects of 1, 25-(OH)(2)-D in primary cultures of human adipocytes, and found significant, sustained increases in intracellular Ca(2+) and a corresponding marked inhibition of lipolysis (EC(50) approximately 50 pM; P<0.001), suggesting that dietary calcium could reduce adipocyte mass by suppressing 1,25-(OH)(2)-D. To test this hypothesis, we placed transgenic mice expressing the agouti gene specifically in adipocytes on a low (0.4%) Ca/high fat/high sucrose diet either unsupplemented or with 25 or 50% of the protein replaced by non-fat dry milk or supplemented to 1.2% Ca with CaCO(3) for 6 wk. Weight gain and fat pad mass were reduced by 26-39% by the three high calcium diets (P<0.001). The high calcium diets exerted a corresponding 51% inhibition of adipocyte fatty acid synthase expression and activity (P<0.002) and stimulation of lipolysis by 3. 4- to 5.2-fold (P<0.015). This concept of calcium modulation of adiposity was further evaluated epidemiologically in the NHANES III data set. After controlling for energy intake, relative risk of being in the highest quartile of body fat was set to 1.00 for the lowest quartile of Ca intake and was reduced to 0.75, 0.40, and 0.16 for the second, third, and fourth quartiles, respectively, of calcium intake for women (n=380;P<0.0009); a similar inverse relationship was also noted in men (n=7114; P<0.0006). Thus, increasing dietary calcium suppresses adipocyte intracellular Ca(2+) and thereby modulates energy metabolism and attenuates obesity risk.

Dietary calcium regulates ROS production in aP2-agouti transgenic mice on high-fat/high-sucrose diets

“…18,19 In addition, 1a, 25-(OH) 2 -D 3 also plays a role in regulating human adipocyte UCP2 expression, suggesting that the suppression of 1a, 25-(OH) 2 -D 3 and the resulting upregulation of UCP2 may contribute to increased rates of energy utilization. 10,11 Accordingly, the suppression of 1a, 25-(OH) 2 -D 3 by increasing dietary calcium attenuates adipocyte triglyceride accumulation and caused a net reduction in fat mass in both mice and humans in the absence of caloric restriction, 13 a marked augmentation of body weight and fat loss during energy restriction in both mice and humans, 13,20 and a reduction in the rate of weight and fat regain following energy restriction in mice. 14 Our previous data demonstrate that 1a, 25(OH) 2 D 3 stimulates Ca 2 þ signaling and suppresses UCP2 expression on human and murine adipocytes 11,14 and suppresses UCP3 expression in skeletal muscle in mice; 14 accordingly, dietary calcium suppression of ROS production is likely due to suppression of circulating 1a, 25(OH) 2 D 3 levels and resultant reductions in Ca 2 þ signaling and increases in UCP2 and UCP3 expression.…”

“…Six mice randomly selected from each group were killed to provide baseline data and the remaining six mice in each group were put on a modified AIN 93 G diet 15 with sucrose as the sole carbohydrate source and providing 64% of energy, and fat increased to 25% of energy with lard as previously described. 13,14 Mice were studied for 9 days, during which food intake and spillage were measured daily and body weight, fasting blood glucose and food consumption assessed weekly. At the conclusion of the study, all mice were killed under isofluorane anesthesia and fat pads were immediately excised, weighed and used for further study, as described below.…”

“…aP2-agouti transgenic mice were used as a model of obesityinduced oxidative stress. We previously described these mice as useful models for diet-induced obesity in a genetically susceptible human population in that they are not obese on a standard AIN-93 G diet, but develop mild to moderate obesity and hyperglycemia when fed high-sucrose and/or high-fat diets, 13,14 indicating that aP2-agouti transgenic mice may be a potential animal model to study obesityassociated oxidative stress. Accordingly, before the dietary calcium experiments, we compared adipose ROS production between aP2 transgenic mice and wild-type mice following short-term exposure to the high-fat-high-sucrose diet in order to verify its suitability as an animal model.…”

Effect of calcium and dairy foods in high protein, energy-restricted diets on weight loss and metabolic parameters in overweight adults

“…Fat pad mass is lower after consumption of diets high in calcium carbonate or dairy calcium compared to an equicaloric, low-calcium, high-fat, high-sucrose diet. 10 Highcalcium diets result in greater loss of total and fat pad mass, increased lipolysis and lower lipogenesis compared to the control diet when the energy intake of obese mice is reduced to 70% of ad libitum consumption. 11 Unintentional weight loss (À4.9 kg of fat mass) occurred after 1 y of increased calcium intake (1000 mg/d) in obese African-Americans.…”

Milk intake is inversely related to obesity in men and in young women: data from the Portuguese Health Interview Survey 1998–1999

“…Several epidemiological and experimental studies have shown that dietary calcium intake is negatively related to body mass index (BMI), both in adults [1][2][3][4] and in children. 5,6 Overall, each 300 mg increment in regular calcium intake is associated with approximately 1 kg less body fat in children, and 2.5-3.0 kg lower body weight in adults.…”