Recently, much attention has been paid to natural plant-derived compounds as an alternative strategy for developing anti-obesity agents with minimal detrimental effects. Among various natural compounds, caffeine (1, 3, 7-trimethyl xanthine) and alpha lipoic acid (1, 2-dithiolane-3-pentanoic acid; LA) are the natural agents which show a promising result in decreasing fat deposit. Moreover, we have improved efficiencies of LA by CaCO3 NPs because LA had low bioavailability. In the present study, we investigated the effect of combination between caffeine and LA-CaCO3 NPs in lipid accumulation reduction and lipolysis stimulation in human subcutaneous adipocytes and human visceral adipocytes. Our results showed that intracellular lipid accumulation in human subcutaneous adipocytes treated with the combination (5 mM caffeine and 600 ?M LA-CaCO3 NPs) were not significantly different from in the groups treated with LA, LA-CaCO3 NPs, and caffeine while the lipid levels in human visceral adipocytes treated with the combination were lower than those in the groups using caffeine and LA alone. Lipolysis was lower in both human subcutaneous adipocytes and human visceral adipocytes that are treated with the combination than that in the groups treated with each alone. These results indicated that combination between caffeine and LA-CaCO3 NPs were not reduced lipid accumulation in subcutaneous adipocytes but they can reduce lipid accumulation in visceral adipocytes. In term lipolysis, the combination were not stimulated lipolysis in both cells. Moreover, we have established a novel LA-CaCO3 NPs that enhance reduction of lipid accumulation and stimulation of lipolysis in both cells. These results propose that CaCO3 NPs has potential effect for using an alternative method for subcutaneous adipocytes and visceral adipocyte lipid reduction.