Effects of mitochondrial uncoupling on adipocyte intracellular Ca(2+) and lipid metabolism

The Journal of Nutritional Biochemistry
Xiaocun Sun, Michael B Zemel

Abstract

Previous data from this laboratory demonstrate that increased intracellular Ca(2+) ([Ca(2+)]i) coordinately regulates human and murine adipocyte lipid metabolism by stimulating lipogenesis and inhibiting lipolysis. However, recent data demonstrate metabolic uncoupling increases [Ca(2+)]i but inhibits lipogenesis by suppressing fatty acid synthase (FAS) activity. Accordingly, we have evaluated the interaction between mitochondrial uncoupling, adipocyte [Ca(2+)]i, and adipocyte lipid metabolism. Pretreatment of 3T3-L1 cells with mitochondrial uncouplers (DNP or FCCP) amplified the [Ca(2+)]i response to depolarization with KCl by 2-4 fold (p <0.001), while this increase was prevented by [Ca(2+)]i channel antagonism with lanthanum. Mitochondrial uncouplers caused rapid (within 4hr) dose-dependent inhibition of FAS activity (p <0.001), while lanthanum caused a further additive inhibition. The suppression of FAS activity induced by uncoupling was reversed by addition of ATP. Mitochondrial uncouplers increased FAS expression significantly while [Ca(2+)]i antagonism with lanthanum decreased FAS expression (P <0.001). In contrast, mitochondrial uncouplers independently inhibited basal and isoproterenol-stimulated lipolysis (20-40%, p <0...Continue Reading

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Citations

Nov 7, 2008·The British Journal of Nutrition·Lucía Pérez-GallardoFrancisca Serra
Apr 13, 2012·Clinical Science·Ramaroson AndriantsitohainaIsmail Laher
Mar 8, 2006·International Journal of Obesity : Journal of the International Association for the Study of Obesity·X Sun, M B Zemel
Aug 9, 2011·Life Sciences·Tomasz Szkudelski, Katarzyna Szkudelska

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