Hydroxycitric Acid‑Induced Activation of Peroxisome Proliferator‑Activated Receptors in 3T3‑L1 Adipocyte Cells

Background: Increase in obesity incidence has become serious threat to civilized human population. Traditional Indian System of Medicines may have many potential leads in managing obesity. (‑)‑Hydroxycitric acid (HCA), a unique compound which is present in Garcinia species, has been safely used for centuries in Southeastern Asia for various purposes. Objective: To determine the effect of HCA treatment on peroxisome proliferator‑activated receptors (PPARs) and their target genes. Materials and Methods: Effect of the calcium salt of HCA on adipogenic transcription factors PPARs and their target genes (lipoprotein lipase, fatty acid synthase, fatty acid binding protein, glucose transporter 4, and adiponectin) during adipogenesis in 3T3‑L1 was investigated. The extent of adipogenesis was checked by measuring the lipid accumulation and glucose uptake in the presence and absence of HCA. Results: HCA treatment modulated the differentiation of adipocytes in a dose‑dependent manner, wherein lower concentrations showed increased accumulation of lipid depots. HCA treatment increased PPARγ and its target genes during adipocyte differentiation, which emphasize the role of HCA in adipocity and obesity. Moreover, the binding conformations of HCA and PPARα and PPARγ were predicted using flexible docking and confirmed with known agonists, which also confirms the bioactivity. Conclusion: HCA decreases circulating lipids through raised levels of adipogenic‑specific genes activated by the PPARs, thereby augmenting adiposity and related complications.