Abstract:Tetracarpidium conophorum nuts are nutrient‐dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low‐grade inflammation. Ethanol whole extract (EWE), ethyl‐acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG‐induced obese rats for 6 weeks (n = 6). Afterward, the RNA synthesis of inflammation‐associated genes was measured, and GC–MS ligands in the extract and fractions were docked against their protein products in silico. The study found that in obese animals, PPAR‐γ and Adiponectin expressions were down‐regulated, while TNF‐α was up‐regulated, indicating an increased low‐grade inflammatory process in adipose tissue. After 6‐week oral treatments with EWE, EAF and RES, PPAR‐γ and Adiponectin expressions increased significantly, while TNF‐α expression decreased, suggesting the modulation of obesity‐induced inflammation in adipose tissue. The in silico molecular docking analysis identified four lead compounds likely responsible for the observed effect, namely 6‐Isopropenyl‐4,8a‐dimethyl‐4a,5,67,8,8a‐hexahydro‐1H‐naphthalen‐2‐one, 9,12,15‐Octadecatrienoic methyl ester (Z,Z,Z), 9,12,15‐Octadecatrienoic acid and Hexanedioic acid, bis(2‐ethylhexyl). Of these compounds, 6‐Isopropenyl‐4,8a‐dimethyl‐4a,5,67,8,8a‐hexahydro‐1H‐naphthalen‐2‐one demonstrated the strongest affinity to the binding cavities of PPARγ (−7.3 kcal/mol), Leptin (−5.2 kcal/mol), Adiponectin (−7.1 kcal/mol) and TNF‐α (−6.3 kcal/mol) and was better than the standard drug, Orlistat (−6.7, −4.4, −6.8 and − 4.5 kcal/mol, respectively). The study reveals that T. conophorum nuts possess bioactive compounds/drug candidates that can exert positive modulation, at the molecular level, the low‐grade inflammatory process associated with obesity, which normally facilitates the outset of complications.
