Masters Theses

Date of Award

12-2002

Degree Type

Thesis

Degree Name

Master of Science

Major

Nutrition

Major Professor

Michael B. Zemel

Committee Members

Jean Skinner, Jung Han Kim

Abstract

We previously demonstrated a regulatory role for intracellular Ca2+([Ca2+]i) in human and murine adipocyte metabolism, with increased [Ca2+]i coordinately stimulating lipogenesis and inhibiting lipolysis, thereby expanding adipocyte lipid mass. More recently, we reported that 1∝, 25-dihydroxyvitamin D3 [1∝, 25-(OH)2-D3] stimulates adipocyte membrane vitamin D receptor (mVDR)-mediated Ca2+ influx, resulting in a similar Ca2+-mediated modulation of adipocyte lipid metabolism. 1∝, 25-(OH)2-D3 also exerts an inhibitory effect on adipocyte uncoupling protein 2 (UCP2) mRNA and protein levels via the nuclear vitamin D receptor (nVDR), independent of its effects on Ca2+ influx, Furthermore, we reported that suppressing 1∝, 25-(OH)2-D3 levels by increasing dietary calcium reduces adipocyte [Ca2+]i, stimulates lipolysis, inhibits lipogenesis, increases thermogenesis, and consequently results in attenuation of adipocyte lipid accretion and weight/fat gain during over-consumption and acceleration of weight/fat loss during energy restriction. Notably, dairy sources of calcium exerted significantly greater effects than calcium in the form of calcium carbonate, although the reason for this is not yet clear. This thesis study was conducted to extend these observations by determining the efficacy of a fermented dairy product, yogurt, presented either unflavored or strawberry-flavored, compared to calcium carbonate, in accelerating weight/fat loss secondary to caloric restriction in aP2-agouti transgenic mice. Mice were fed a low calcium (0.4%)/high fat/high sucrose diet for 6 weeks in order to induce obesity. Mice were then either maintained on the same low calcium basal diet ad lib or energy-restricted (70% of ad lib) on this diet either unsupplemented (basal) or supplemented with calcium content increased to 1.2% either by replacing 34% of the protein with spray dried plain or strawberry-flavored yogurt (with macronutrient adjustments) or by adding calcium carbonate for 6 weeks. Adipocyte [Ca2+]i was only slightly decreased by energy restriction alone but was further markedly reduced by all three high calcium diets (170±6 nM, n=10 vs. 60±5 nM, n=30, p<0.001). The three high calcium diets caused significant stimulation of both basal and isoproterenol-stimulated lipolysis (78%-137%, p<0.05), with yogurt exerting a significantly greater effect compared to calcium carbonate (p<0.05). Similarly, the three high calcium diets suppressed adipocyte FAS mRNA by an average of 87%. Body weight, as well as individual and total fat pad weight, reflected these changes, with a 45% augmentation in fat loss on the two yogurt diets compared to that on the low calcium diet secondary to caloric restriction (p<0.001). Calcium carbonate supplementation produced an intermediate effect, with a lower 28% augmentation in fat loss compared to that on the low calcium diet secondary to caloric restriction. Furthermore, high calcium diets caused a higher core temperature and an increased white adipose tissue UCP2 expression, indicating increased thermogenesis and decreased metabolic efficiency. In conclusion, our data show that dietary calcium with calcium sources from plain yogurt, strawberry-flavored yogurt and calcium carbonate supplement suppress adipocyte [Ca2+]i and up-regulate UCP2 via the suppression of 1∝, 25-(OH)2-D3, and thereby reduce energy storage, decrease metabolic efficiency and accelerate weight/fat loss during energy restriction, with significantly greater effects exerted by yogurt than by supplemented calcium. Consistent with the animal observations, accumulating human studies strongly support an anti-obesity role for dietary calcium. Therefore, dietary calcium, especially dairy calcium, may be effective dietary regimen for the treatment of obesity.

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