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Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMPK signaling pathway

Published online by Cambridge University Press:  11 May 2021

Long Cheng
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Jingkang Wang
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Yongcheng An
Affiliation:
College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
Hongyu Dai
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Yuhui Duan
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Lu Shi
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Yinglan Lv
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Huimin Li
Affiliation:
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Chen Wang
Affiliation:
College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
Haifeng Du
Affiliation:
The Third Municipal Hospital of Chengde, 067000, Chengde, China
Xiaoqing Zhong
Affiliation:
Guilin Sanjin Pharmaceutical Co., Ltd., Guilin, 541004, China
Baosheng Zhao
Affiliation:
Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Corresponding
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Abstract

The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experiment results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats including reducing body weight (BW) gain, Lee’s index, food intake, inguinal white adipose tissue (IWAT) accumulation, blood lipid fasting insulin level and fasting blood glucose level, increasing the ratios of brown adipose tissue (BAT) mass to BW, and improving insulin sensitivity and liver function. In addition, mulberry leaf induced browning of IWAT by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated BAT by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT1) protein in both IWAT and BAT via a mechanism involving Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.

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© The Authors 2021
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Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMPK signaling pathway
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Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMPK signaling pathway
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