4.5 Article

Tanshinone IIA and its derivative activate thermogenesis in adipocytes and induce beiging of white adipose tissue

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 544, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2022.111557

Keywords

Tanshinone; Obesity; Metabolic disorder; AMPK; PGC-1 alpha

Funding

  1. Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population [2018B030322003KF01]
  2. Shenzhen Science and Technology Project [JCYJ20190807154205627]
  3. Guangdong Natural Science Fund [2020A1515010365]
  4. Guangzhou Science and Technology Project [201807010069]

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In this study, the effects of TAN2A and TAN20 on adipogenesis, lipid metabolism, and thermogenesis were investigated. Both TAN2A and TAN20 were found to increase mitochondria content in adipose tissue, enhance energy expenditure, reduce body weight, and improve insulin sensitivity and metabolic homeostasis in obese and diabetic mouse models. TAN20 was also shown to promote the transformation from white to beige adipose tissue and activate brown adipose tissue. The increased expression of UCP1 and other thermogenic genes in adipocytes was mediated through the AMPK-PGC-1alpha signaling pathway.
Tanshinone IIA (TAN2A) is a major active ingredient of Salvia miltiorrhiza used in traditional Chinese medicine and tanshinone 20 (TAN20) is a derivative of TAN2A. In this study, we examined the effects of TAN2A and TAN20 on adipogenesis, lipid metabolism, and thermogenesis. Our experiments showed that both TAN2A and TAN20 increased mitochondria content in adipose tissue, enhanced energy expenditure, reduced body weight, and improved insulin sensitivity and metabolic homeostasis in obese and diabetic mouse models. We demonstrated that TAN20 can facilitate the transformation from white to beige adipose tissue, as well as activate brown adipose tissue. In uncoupling protein 1 (UCP1) knockout mouse model, the effects of TAN2A and TAN20 on body weight and glucose tolerance were not observed, suggesting that such effects were UCP1 dependent. Furthermore, we found that TAN2A and TAN20 increased the expression of UCP1 and other thermogenic genes in adipocytes through AMPK-PGC-1 alpha signaling pathway. Our findings indicate that TAN2A and its derivative TAN20 are potential interesting energy expenditure regulators and may be implicated in treatment of obesity and other metabolic disorders.

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