In vitro and in vivo effects of Momordica cochinchinensis Lour. Spreng carotenoid-rich fruit extracts on adipogenesis

Momordica cochinchinensis (Gac fruit) is noted for its high carotenoid content, particularly lycopene and beta-carotene, known for their potent antioxidant properties. Despite these benefits, the anti-obesity potential of Gac fruit remains underexplored. This study investigates the effects of Gac fruit extracts (GFE) and Gac aril carotenoids-rich extracts (GACRE) on adipogenesis, utilizing mouse embryo fibroblast cells (3T3-L1 preadipocytes) lines and Sprague-Dawley (SD) rats. The GFE and GACRE were obtained using a carotenoid extraction method involving a mixture of n-hexane, acetone, and ethanol (50:25:25 v/v/v) to achieve the highest yield (38.96%). The carotenoid levels and antioxidant activity of Gac fruit components (peel, pulp, and aril) were quantified, and the impacts of these extracts on lipid accumulation, intracellular triglyceride levels, adipocyte differentiation, and porcine pancreatic lipase inhibition in vitro were examined. Additionally, the effects of GACRE on biochemical parameters, adipose tissue mass, adipocyte hyperplasia and hypertrophy, liver and kidney histology, and peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding proteins (C/EBPs), and uncoupling protein 1 (UCP1) genes expression in SD rats fed a high-fat diet (HFD) (40% fat) were assessed. Chemical analysis revealed the highest concentrations of lycopene (31.7–103.7 mg/g), astaxanthin (3.23–4.91 mg/g), zeaxanthin (0.52–1.49 mg/g), and lutein (0.20–1.35 mg/g) in the aril, while β-carotene (3.58–9.64 mg/g) was predominant in the peel. The antioxidant activity, measured by DPPH assay, showed significant activity across all fruit parts, with peel, pulp, and aril demonstrating varying degrees of free radical scavenging and IC50 values. In vitro, GFE significantly reduced lipid accumulation and triglyceride levels in 3T3-L1 adipocytes, with the pulp extract showing the greatest effect. GFE concentrations above 200 µg/mL drastically decreased cell viability, indicating a dose-dependent inhibition of adipogenesis. GFE also demonstrated significant porcine pancreatic lipase inhibition. In vivo, rats fed HFD with GACRE-50 (low dose) and GACRE-200 (high dose) did not show significant body weight reduction. However, GACRE-200 treatment significantly lowered aspartate transaminase levels, and both doses markedly reduced creatine levels by approximately 50%. No substantial differences were observed in pancreatic markers (amylase and lipase). GACRE-200 significantly decreased blood glucose, creatine kinase, and triglyceride levels by 32.17%, 22.16%, and 31.30%, respectively. Although GACRE treatment did not significantly reduce adipocyte hyperplasia and hypertrophy in white and brown adipose tissues (WAT/BAT), it resulted in notable histological changes in the liver and kidneys. High-dose GACRE induced microvesicular steatosis and hepatic sinusoidal congestion while potentially preventing glomerulus dysfunction. Gene expression analysis revealed elevated PPARγ and UCP1 expression in brown adipose tissue relative to white adipose tissue, correlating with increased BAT numbers and enhanced thermogenesis. In conclusion, Gac fruit exhibits promising anti-obesity properties attributed to its high carotenoid and antioxidant content. GFE effectively reduced lipid accumulation, triglyceride content, and demonstrated significant porcine pancreatic lipase inhibition in vitro, preventing adipogenesis in a dose-dependent manner. Enhanced thermogenesis and UCP1 activation, driven by higher BAT counts, contribute to the anti-obesity effects of GACRE. These findings highlight the potential of Gac fruit carotenoids as natural agents in obesity management.

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