Sesamol Alleviates Obesity-Related Hepatic Steatosis via Activating Hepatic PKA Pathway

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.

Sesamol ameliorates hepatic lipid accumulation and oxidative stress in steatosis HepG2 cells via the PPAR signaling pathway

“…Figure 4a The up-regulated PPARα and CPT-1A transcriptions were in line with the above results that the amounts of the TG and fat droplets in hepatocytes were lowered by sesamol intervention, suggesting that sesamol potently reduced intracellular fat accumulation by promoting lipolysis. These data agreed with previous publications that PPARα and CPT-1A levels for fatty acid β-oxidation were markedly increased by sesamol treatment in the liver of HFD-induced obese mice (Xu et al, 2020). Moreover, Qin et al (2019) reported that sesamol showed a positive effect on obesity-associated metabolic disorders by improving the expression of CPT-1A.…”

Sesamol promotes browning of white adipocytes to ameliorate obesity by inducing mitochondrial biogenesis and inhibition mitophagy via β3-AR/PKA signaling pathway

“…Eight-week-old male C57BL/6J mice were obtained from Central South University (Hunan, Changsha, China) and maintained under standard laboratory conditions (20–24°C, 40–60% humidity, and light and dark cycle: 12 h/12 h). As previously described ( 25 ), the mice were given 1 week to allow them to adapt to the new environment and allowed free access to water and food. Then, one group was fed a normal-fat diet (NFD), forming the control group ( n = 10), and all other mice received a high-fat diet (HFD group) for 8 weeks to establish the obese model.…”

“…As previously described ( 25 ), after 16 weeks, blood samples were collected from the femoral artery of the mice and stored overnight at 4°C. Then the serum was separated by centrifuging the samples at 3,000 × rpm for 15 min.…”

“…Recent studies have indicated that sesamol, a lignan from sesame oil, had shown potential beneficial functions in obesity treatment (21)(22)(23)(24). Our previous research demonstrated that sesamol could attenuate obesity-associated metabolic disorders by activating the PKA pathway in liver (25). Apart from this, there were some observations that sesamol could upgrade the cognitive function by inhibiting the production of amyloid protein in central nervous system of mice (26).…”

Chronic Transient Hypoxia Alleviates High Fat Diet-Induced Obesity and Fatty Liver in C57 Mice by Upregulating Epinephrine Levels and Activation of AMPK

“…β3-AR, act as an isoform of the adrenergic receptor, initiates the activation of protein kinase A (PKA) [14]. It is well established that PKA is closely related to lipolysis [15], accomplished by activating the AMPK pathway, reducing lipid production, increasing fatty acid βoxidation, and bene cial for improving liver lipid metabolism [16]. AMPK is a universal metabolic sensor that has a crucial role in maintaining lipid homeostasis [17], regulate fatty acid β-oxidation by activating PGC-1α [18], Moreover, the activation of AMPK can also boost the expression of CD206, which is highly expressed in M2 macrophages [19], and transform macrophages from a pro-in ammatory M1 phenotype to an anti-in ammatory M2 phenotype, subsequent reduction the deleterious in ammation [20].…”