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Anti-obesity potential of 4,4-dimethylsterols by inhibiting pancreatic
 lipase

This study purified three classes of phytosterols from the unsaponifiable matter
 of different vegetable oils using preparative chromatography. Subsequently, their
 anti-obesity activity and lipase inhibitory activity were compared using in vivo mice
 model, in vitro digestion, and molecular docking. Results indicated that the
 4,4-dimethylsterols displayed higher anti-obesity ability through promoting fecal
 triacylglycerol excretion and improving fatty acid profiles in adipose tissues. In
 contrast, the 4-demthylsteols showed higher cholesterol-lowering activity. In vitro
 digestion further proved the 4,4-dimethylsterols significantly decreased the hydrolysis
 activity of pancreatic lipase, achieving a higher fatty acid release than
 4-desmethylsteorls. Finally, the inhibitory mechanism was proposed as that the
 4,4-dimethylsterols possess a hydrogen-binding interaction with the Ser153 in the lipase
 catalytic pocket, presumably due to the polarity of hydroxyl group shielded by the two
 methyl groups in the structure. Overall, the present work concluded that the inhibitory
 activity on pancreatic lipase by 4,4-dimethylsterols can potentially ameliorate
 diet-induced obesity.