Transcriptome of Primary Adipocytes from Obese Women in Response to a Novel Hydroxycitric Acid–Based Dietary Supplement

Abstract

Obesity is a global public health problem. Traditional herbal medicines may have some potential in managing obesity. The dried fruit rind of Garcinia cambogia, also known as Malabar tamarind, is a unique source of (-)-hydroxycitric acid (HCA), which exhibits a distinct sour taste and has been safely used for centuries in Southeastern Asia to make meals more filling. Recently it has been demonstrated that when taken orally, a novel, highly soluble calcium/potassium salt of HCA (HCA-SX) is safe and bioavailable in the human plasma. Although HCA-SX seems to be conditionally effective in weight management in experimental animals and in humans, its mechanism of action remains unclear. In this study, subcutaneous preadipocytes collected from obese women with body mass index>25 kg/m2 were differentiated to adipocytes for 2 weeks in culture. The effects of low-dose HCA-SX on lipid metabolism and on the adipocyte transcriptome were tested. HCA-SX augmented isoproterenol- and 3-isobutyryl-1-methylxanthine-induced lipolysis. Using oil red O, the production of lipid storage droplets by the cultured mature human adipocytes was visualized and enumerated. HCA-SX caused droplet dispersion facilitating lipase action on the lipids. HCA-SX markedly induced leptin expression in the adipocytes. In the microarray analyses, a total of 54,676 probe sets were screened. HCA-SX resulted in significant down-regulation of 348, and induction of 366 fat- and obesity-related genes. HCA-SX induced transactivation of hypoxia inducible factor (HIF), a novel approach in the management of obesity. Taken together, the net effects support the antilipolytic and antiadipogenic effects of HCA-SX. Further human studies are warranted.