PMID- 33971987 OWN - NLM STAT- MEDLINE DCOM- 20220427 LR - 20220427 IS - 1475-2662 (Electronic) IS - 0007-1145 (Linking) VI - 127 IP - 6 DP - 2022 Mar 28 TI - Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMP-activated protein kinase signalling pathway. PG - 810-822 LID - 10.1017/S0007114521001537 [doi] AB - 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 experimental results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats. In addition, mulberry leaf induced browning of inguinal white adipose tissue (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-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), 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 brown adipose tissue (BAT) by increasing the expressions of brown-mark genes including UCP1, PGC-1alpha, PPARalpha, 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 (CPT-1) proteins in both IWAT and BAT via a mechanism involving AMP-activated protein kinase (AMPK) and PGC-1alpha 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. FAU - Cheng, Long AU - Cheng L AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Wang, Jingkang AU - Wang J AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - An, Yongcheng AU - An Y AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Dai, Hongyu AU - Dai H AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Duan, Yuhui AU - Duan Y AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Shi, Lu AU - Shi L AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Lv, Yinglan AU - Lv Y AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Li, Huimin AU - Li H AD - Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Wang, Chen AU - Wang C AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China. FAU - Du, Haifeng AU - Du H AD - The Third Municipal Hospital of Chengde, 067000 Chengde, People's Republic of China. FAU - Zhong, Xiaoqing AU - Zhong X AD - Guilin Sanjin Pharmaceutical Co. Ltd, Guilin 541004, People's Republic of China. FAU - Zhao, Baosheng AU - Zhao B AD - Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210511 PL - England TA - Br J Nutr JT - The British journal of nutrition JID - 0372547 RN - 0 (PPAR alpha) RN - 0 (Uncoupling Protein 1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/genetics/metabolism MH - Adipose Tissue, Brown/metabolism MH - Adipose Tissue, White/metabolism MH - Animals MH - *Diabetes Mellitus, Experimental/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - *Morus/metabolism MH - PPAR alpha/metabolism MH - Plant Leaves MH - Rats MH - Uncoupling Protein 1/genetics/metabolism OTO - NOTNLM OT - AMP-activated protein kinase signalling pathway OT - Brown adipose tissue OT - Browning of white adipose tissue OT - Mulberry leaf OT - Type 2 diabetes mellitus OT - White adipose tissue EDAT- 2021/05/12 06:00 MHDA- 2022/04/28 06:00 CRDT- 2021/05/11 05:45 PHST- 2021/05/12 06:00 [pubmed] PHST- 2022/04/28 06:00 [medline] PHST- 2021/05/11 05:45 [entrez] AID - S0007114521001537 [pii] AID - 10.1017/S0007114521001537 [doi] PST - ppublish SO - Br J Nutr. 2022 Mar 28;127(6):810-822. doi: 10.1017/S0007114521001537. Epub 2021 May 11.