Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.
10.1016/S1875-5364(23)60481-9
- Author:
Long CHENG
1
,
2
;
Lu SHI
3
;
Changhao HE
3
;
Chen WANG
4
;
Yinglan LV
3
;
Huimin LI
3
;
Yongcheng AN
4
;
Yuhui DUAN
3
;
Hongyu DAI
3
;
Huilin ZHANG
3
;
Yan HUANG
4
;
Wanxin FU
4
;
Weiguang SUN
5
;
Baosheng ZHAO
6
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
2. Department of Pharmacognosy, School of Pharmacy, China Medical University, Shenyang 110122, China.
3. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
4. College of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
5. GuangZhou Baiyunshan Xingqun Pharmaceutical Co., Ltd., Guangzhou 510288, China. Electronic address: suntcm@163.com.
6. Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: zhaobs1973@163.com.
- Publication Type:Journal Article
- Keywords:
AMPK/SIRT1/PGC-1α;
Brown adipose tissue;
Browning of white adipose tissue;
Mulberry leaf flavonoids;
Type 2 diabetes
- MeSH:
Mice;
Animals;
Adipose Tissue, Brown;
Sirtuin 1/pharmacology*;
Diabetes Mellitus, Type 2/metabolism*;
AMP-Activated Protein Kinases/metabolism*;
Morus/metabolism*;
Flavonoids/metabolism*;
Prospective Studies;
Signal Transduction;
Adipose Tissue, White;
Plant Leaves;
Uncoupling Protein 1/metabolism*;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(11):812-829
- CountryChina
- Language:English
-
Abstract:
Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
