In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased β-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.

Purpose Prolonged sitting is associated with cardiometabolic complications. The study purpose was to investigate whether breaking up prolonged sitting with brief stair climbing exercise “snacks” could lower postprandial insulin, glucose, and free fatty acids responses. Methods In two separate randomized crossover studies, 12 young healthy-weight men (study 1) and 11 adults with overweight/obesity (OW; study 2) completed two experimental conditions: i) sedentary (SED; 9-h sitting) and ii) stair climbing snacks (SS; 8 × 15–30 s once per hour). The same high-glycemic index meals were consumed at 0, 3, and 6 h at each condition. The primary outcome was total insulin area under the curve (AUC) across 9 h. Results In healthy-weight men, there were no significant differences between SS and SED for total (9-h) insulin AUC (P = 0.24, d = 0.4), total glucose AUC (P = 0.17, d = 0.48), total nonesterified fatty acid (NEFA) AUC (P = 0.22, d = 0.4), or total triglyceride AUC (P = 0.72). In adults with OW, total insulin AUC (−16.5%, P = 0.036, d = 0.94) and total NEFA AUC (−21%, P = 0.016, d = 1.2) were significantly lower in SS versus SED. No differences were found for total glucose and triglyceride AUC (all, P > 0.31) in participants with OW. Conclusions Breaking up 9 h of prolonged sitting with hourly brief stair climbing exercise snacks lowered postprandial insulin and NEFA levels in adults with overweight/obesity.

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While different polyphenols similarly decreased cellular ROS in this model of steatosis, they differed in their ability to suppress TNF-α expression and induce mitochondrial biogenesis and content.

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