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

Abstract

We have demonstrated previously a regulatory role for intracellular Ca2+ ([Ca2+]i) in adipocyte lipogenesis and lipolysis and have recently reported that 1,25-(OH)2-D increases adipocyte [Ca2+]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 [Ca2+]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 [Ca2+]i pad 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 CaCO3 to 1.2% Ca for six weeks. Adipocyte [Ca2+]i was unaffected by Kcal restriction but was reduced markedly by all three high Ca diets (290 vs. 130 nM, p2+]i and thereby reduce energy storage and increase thermogenesis during Kcal restriction.

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

“…Weight loss in subjects consuming an energyrestricted diet that had a moderate level of protein and lowcalcium content (16% energy from protein, 600 mg Ca/d) was equal to subjects consuming an equicaloric diet that was higher in both protein and calcium (27% energy from protein, 1600 mg Ca/d). 11 Weight reduction in obese women was the same in calcium-supplemented (1800 mg Ca/d) and placebo groups (800 mg Ca/d). 12 Our findings contrast a weight loss study (energy deficit of À2 MJ/d for 24 wk) in obese adults where weight loss of subjects allocated to a high dairy diet (1200-1300 mg Ca/d, n ¼ 11) was À10.9% compared to À8.6% in a supplemental calcium group (1200-1300 mg Ca/d, n ¼ 11) and À6.5% in a low-calcium group (500 mg Ca/d, n ¼ 10).…”

“…Two standard servings of alcohol (10 g alcohol/serving) were permitted per wk. EB was achieved by increasing energy intake by 2 MJ/d for each 0.5 kg weight loss per wk (averaged over wk [8][9][10][11][12]. 17 Subjects were provided with a prescriptive meal plan.…”

“…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. 10 Overweight adults following an energy-restricted (À2000 kJ/d) diet that was high in dairy foods/calcium (1200-1300 mg Ca/d) had greater loss of total body weight and fat mass compared to a calcium-supplemented group (1200-1300 mg/d), and the latter group's weight loss was greater than a low-calcium, placebo-treated group (400-500 mg Ca/d).…”

1α, 25-Dihydroxyvitamin D and corticosteroid regulate adipocyte nuclear vitamin D receptor

“…[1][2][3] We have shown that 1a, 25-dihydroxyvitamin D mediates increases in intracellular calcium ([Ca 2 þ ]i) in adipocytes via the 1a, 25-dihydroxyvitamin D-membraneassociated rapid response steroid hormone (1, 25D 3 -MARRS) binding protein, stimulates lipogenesis and inhibit lipolysis via a calcium-dependent mechanism. 4,5 We have also shown a dose-responsive inhibition of uncoupling protein 2 expression by 1a, 25-dihydroxyvitamin D in adipocytes; this is a genomic effect, presumably mediated by the nuclear vitamin D receptor (nVDR).…”

Calcium plus vitamin D supplementation and fat mass loss in female very low-calcium consumers: potential link with a calcium-specific appetite control

“…Indeed, based on results showing that women consuming less than 600 mg calcium/d had an increased percentage body fat (4) , the existence of a threshold of usual calcium intake below which a supplementation in this mineral would effectively promote fat mass loss is possible. The first objective of the present study was to investigate this hypothesis and to assess the impact of a calcium plus vitamin D (calciumþD) supplementation on the outcome of a weightreducing programme in female low-and very low-calcium consumer (VL-CC) overweight/obese subjects.Up to now, the potential effect of calcium on energy balance and adiposity has been explained by a suppression of calcitriol (1,25-dihydroxyvitamin D) which decreases intra-adipocyte calcium influx and concentration (5) leading to a reduced lipogenic gene expression and stimulation of lipolysis and adipocytes uncoupling protein 2 expression (6,7) .Moreover, a diet high in calcium was also shown to increase 24 h lipid oxidation (8) and to reduce lipid absorption due to the intestinal formation of calcium-fatty acids insoluble 'soaps' that are excreted in the faeces (9) . From another perspective, the idea of a 'calcium-specific appetite control' was proposed by Tordoff (10) who documented the possibility that low calcium intake or stores might trigger episodes of increased desire to eat and stimulate motivation to seek out or choose calcium-containing items, and potentially other nutrients and/or food 'recognised' as calcium-rich (10) .…”