From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Sun Jun 11 2000 - 12:10:11 MDT
FASEB J 14(9): 1132-1138 Jun 2000
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) 50pM;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 expresing 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 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.
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