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This study aimed to investigate the effect of sesamol (SEM) on the protein kinase A (PKA) pathway in obesity-related hepatic steatosis treatment by using high-fat diet (HFD)-induced obese mice and a palmitic acid (PA)-treated HepG2 cell line. SEM reduced the body weight gain of obese mice and alleviated related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation. Furthermore, lipid accumulation in the liver and HepG2 cells was reduced by SEM. SEM downregulated the gene and protein levels of lipogenic regulator factors, and upregulated the gene and protein levels of the regulator factors responsible for lipolysis and fatty acid β-oxidation. Meanwhile, SEM activated AMP-activated protein kinase (AMPK), which might explain the regulatory effect of SEM on fatty acid β-oxidation and lipogenesis. Additionally, the PKA-C and phospho-PKA substrate levels were higher after SEM treatment. Further research found that after pretreatment with the PKA inhibitor, H89, lipid accumulation was increased even with SEM administration in HepG2 cells, and the effect of SEM on lipid metabolism-related regulator factors was abolished by H89. In conclusion, SEM has a positive therapeutic effect on obesity and obesity-related hepatic steatosis by regulating the hepatic lipid metabolism mediated by the PKA pathway.

BackgroundObesity has currently become a serious social problem to be solved. Sesamol, a natural bioactive substance extracted from sesame oil, has shown multiple physiological functions, and it might have an effect on the treatment of obesity.ObjectiveThis study was conducted to investigate the therapeutic effect and potential mechanisms of sesamol on the treatment of obesity and metabolic disorders in high-fat diet (HFD)-induced obese mice.MethodsC57BL/6J male mice were fed HFD for 8 weeks to induce obesity, followed by supplementation with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage) for another 4 weeks. Hematoxylin and eosin staining was used to observe lipid accumulation in adipose tissues and liver. Chemistry reagent kits were used to measure serum lipids, hepatic lipids, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. ELISA kits were used to determine the serum insulin and free fatty acid (FFA) levels. Western blotting was used to detect the protein levels involved in lipid metabolism in the liver.ResultsSesamol significantly reduced the body weight gain of obese mice and suppressed lipid accumulation in adipose tissue and liver. Sesamol also improved serum and hepatic lipid profiles, and increased insulin sensitivity. In the sesamol-treated group, the levels of serum ALT and AST decreased significantly. Furthermore, after sesamol treatment, the hepatic sterol regulatory element binding protein-1 (SREBP-1c) decreased, while the phosphorylated hormone sensitive lipase (p-HSL), the carnitine palmitoyltransferase 1α (CPT1α), and the peroxisome proliferator-activated receptor coactivator-1α (PGC1α) increased, which were responsible for the fatty acid synthesis, lipolysis, and fatty acid β-oxidation, respectively.ConclusionsSesamol had a positive effect on anti-obesity and ameliorated the metabolic disorders of obese mice. The possible mechanism of sesamol might be the regulation of lipid metabolism in the liver.

Cardiovascular disease (CVD) is a major global cause of mortality, which has prompted numerous studies seeking to reduce the risk of heart failure and sudden cardiac death. While regular physical activity is known to improve CVD associated morbidity and mortality, the optimal duration, frequency, and intensity of exercise remains unclear. To address this uncertainty, various animal models have been used to study the cardioprotective effects of exercise and related molecular mechanism such as the mice training models significantly decrease size of myocardial infarct by affecting Kir6.1, VSMC sarc-KATP channels, and pulmonary eNOS. Although these findings cement the importance of animal models in studying exercise induced cardioprotection, the vast assortment of exercise protocols makes comparison across studies difficult. To address this issue, we review and break down the existent exercise models into categories based on exercise modality, intensity, frequency, and duration. The timing of sample collection is also compared and sorted into four distinct phases: pre-exercise (Phase I), mid-exercise (Phase II), exercise recovery (Phase III), and post-exercise (Phase IV). Finally, because the life-span of animals so are limited, small changes in animal exercise duration can corresponded to untenable amounts of human exercise. To address this limitation, we introduce the Life-Span Relative Exercise Time (RETlife span) as a method of accurately defining short-term, medium-term and long-term exercise relative to the animal’s life expectancy. Systematic organization of existent protocols and this new system of defining exercise duration will allow for a more solid framework from which researchers can extrapolate animal model data to clinical application.

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