Modulation of Lipogenesis by <i>Tetracarpidium conophorum</i> Nuts via SREBP-1/ACCA-1/FASN Inhibition in Monosodium-Glutamate-Induced Obesity in Rats

Abstract

Objectives This study aimed to investigate the modulatory effects of Tetracarpidium conophorum (African walnut) nuts on lipogenesis in adipocytes and hepatocytes by targeting the SREBP-1/ACCA-1/FASN signaling axis, which plays a pivotal role in obesity-associated lipid metabolism. Methods Obesity was induced in rats over 36 weeks, after which groups were treated with whole extract (WE), ethyl acetate fraction (EA), residue (RES) of T. conophorum nuts, or Orlistat (5.14 mg/kg). Post-treatment, hepatic and adipose tissues were collected and analyzed for gene expression levels of SREBP-1, ACCA-1, and FASN using PCR. Additionally, GC-MS-identified compounds from the nut extracts were subjected to molecular docking against the target proteins, and their drug-likeness and ADMET profiles were evaluated. Results Treatment with WE, EA, and RES significantly downregulated the expression of SREBP-1 and FASN in both hepatic and adipose tissues compared to the obese control. ACCA-1 expression in the adipose tissue was not significantly affected, but hepatic overexpression was significantly attenuated by WE (p &lt; 0.05), EA (p &lt; 0.01), and RES (p &lt; 0.01). Molecular docking revealed strong binding affinities and stable interactions between bioactive compounds and the target proteins. Notably, 6-Isopropenyl-4,8a-dimethyl-4a,5,6,7,8,8a-hexahydro-1H-naphthalen-2-one exhibited the strongest binding affinities to SREBP-1 (−7.7 kcal/mol), ACCA-1 (−7.2 kcal/mol), and FASN (−7.8 kcal/mol), outperforming Orlistat (−5.9 to −6.2 kcal/mol). Drug-likeness assessments and ADMET predictions supported the therapeutic potential of the compounds. Conclusion T. conophorum nuts demonstrate significant anti-obesity potential through the inhibition of hepatic and adipose lipogenesis via downregulation of the SREBP-1/ACCA-1/FASN signaling pathway, with specific bioactive compounds showing promising molecular interactions and pharmacokinetic properties.