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

  • Cui Lin Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China https://orcid.org/0000-0002-2331-6580
  • Jihua Chen Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
  • Minmin Hu Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
  • Wenya Zheng Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
  • Ziyu Song Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
  • Hong Qin Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, Hunan, China https://orcid.org/0000-0002-4578-5118
Keywords: sesamol;, obesity;, beige adipocytes;, mitochondrial biogenesis;, mitophagy

Abstract

Background: Obesity is defined as an imbalance between energy intake and expenditure, and it is a serious risk factor of non-communicable diseases. Recently many studies have shown that promoting browning of white adipose tissue (WAT) to increase energy consumption has a great therapeutic potential for obesity. Sesamol, a lignan from sesame oil, had shown potential beneficial functions on obesity treatment.

Objective: In this study, we used C57BL/6J mice and 3T3-L1 adipocytes to investigate the effects and the fundamental mechanisms of sesamol in enhancing the browning of white adipocytes to ameliorate obesity. Methods: Sixteen-week-old C57BL/6J male mice were fed high-fat diet (HFD) for 8 weeks to establish the obesity models. Half of the obese mice were administered with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage for another 8 weeks. Triacylglycerol (TG) and total cholesterol assay kits were used to quantify serum TG and total cholesterol (TC). Oil red O staining was used to detect lipid droplet in vitro. Mito-Tracker Green was used to detect the mitochondrial content. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of beige-specific genes. Immunoblotting was used to detect the proteins involved in beige adipocytes formation.

Results: Sesamol decreased the content of body fat and suppressed lipid accumulation in HFD-induced obese mice. In addition, sesamol significantly upregulated uncoupling protein-1 (UCP1) protein in adipose tissue. Further research found that sesamol also significantly activated the browning program in mature 3T3-L1 adipocytes, manifested by the increase in beige-specific genes and proteins. Moreover, sesamol greatly increased mitochondrial biogenesis, as proved by the upregulated protein levels of mitochondrial biogenesis, and the inhibition of the proteins associated with mitophagy. Furthermore, β3-adrenergic receptor (β3-AR), protein kinase A-C (PKA-C) and Phospho-protein kinase A (p-PKA) substrate were elevated by sesamol, and these effects were abolished by the pretreatment of antagonists β3-AR.

Conclusion: Sesamol promoted browning of white adipocytes by inducing mitochondrial biogenesis and inhibiting mitophagy through the β3-AR/PKA pathway. This preclinical data promised the potential to consider sesamol as a metabolic modulator of HFD-induced obesity.

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Published
2021-05-10
How to Cite
Lin, C., Chen, J., Hu, M., Zheng, W., Song, Z., & Qin, H. (2021). Sesamol promotes browning of white adipocytes to ameliorate obesity by inducing mitochondrial biogenesis and inhibition mitophagy via β3-AR/PKA signaling pathway. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.7577
Section
Original Articles