Abstract
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.
Highlights
Obesity is a prevalent metabolic disease worldwide and has become an important public health concern [1]
It is reported that obesity commonly plays a direct role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), which is strongly linked to related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation [2,3]
We found that serum TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) levels were significantly reduced, while the high-density lipoprotein cholesterol (HDL-C) level was increased by SEM compared with the high-fat diet (HFD) group (Table 2), which demonstrated that SEM could ameliorate obesity-related dyslipidemia
Summary
Obesity is a prevalent metabolic disease worldwide and has become an important public health concern [1]. It is reported that obesity commonly plays a direct role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), which is strongly linked to related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation [2,3]. Hepatic steatosis is the main pathological feature of NAFLD and the key cause of more severe and progressive disease [5]. There is an urgent need to seek an effective strategy to alleviate hepatic steatosis, which will be instrumental in blocking the further progression of NAFLD. The specific mechanism of obesity-induced hepatic steatosis remains unclear, which makes it difficult to treat NAFLD. Hepatic steatosis is characterized by excessive lipid accumulation in the liver. Hepatic steatosis occurs when hepatic lipid homeostasis is disrupted by obesity, which
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