A phytoestrogen secoisolariciresinol diglucoside induces browning of white adipose tissue and activates non-shivering thermogenesis through AMPK pathway. (August 2020)

• Record Type: Journal Article
• Authors: Kang, JongWook; Park, Jinbong; Park, Woo Yong; Jiao, Wenjun; Lee, Sujin; Jung, Yunu; Youn, Dong-Hyun; Song, Gahee; Cho, Seon Yeon; Kim, Whi Young; Park, Ja Yeon; Ahn, Kwang Seok; Kwak, Hyun-Jeong; Um, Jae-Young
• Is Part Of: Pharmacological research. Volume 158(2020)
• Publication Date: 2020-08
• Subjects: ACC acetyl-CoA carboxylase -- ALT alanine transaminase -- AST aspartate aminotransferase -- ATGL adipose triglyceride lipase -- AMPK AMP-activated protein kinase α: BAT, brown adipose tissue -- C/EBPa CCAAT/enhancer-binding protein a -- CIDEA cell death activator -- COX-2 cyclooxygenase-2 -- COX4 cytochrome c oxidase subunit 4 -- COX8 cytochrome c oxidase subunit 8 -- CPT1 carnitine palmitoyltransferase 1 -- CytoC cytochrome c -- eWAT epididymal white adipose tissue -- FIS1 mitochondrial fission 1 -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- HDL high density lipoprotein density lipoprotein -- H&E hematoxylin and eosin -- HFD high-fat diet -- HSL hormone-sensitive lipase -- IF immunofluorescence -- iWAT inguinal white adipose tissue -- LDL low density lipoprotein -- LKB1 liver kinase B1 -- MFN1 mitofusin-1 -- MTS 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium -- ND normal diet -- NRF1 nuclear respiratory factor 1 -- OGTT oral glucose tolerance test -- PGC1a peroxisome proliferator activated receptor g-coactivator 1-a -- PPARg peroxisome proliferator activated receptor g -- PRDM16 PR domain containing 16 -- SCD1 stearoyl-CoA desaturase-1 -- SDG secoisolariciresinol diglucoside -- siRNA small interfering RNA -- SIRT3 sirtuin-3 -- SREBP1 sterol regulatory element-binding protein 1 -- TC total cholesterol -- TG triglyceride -- UCP1 uncoupling protein 1 -- WAT white adipose tissue -- WT wild type; Secoisolariciresinol diglucoside (SDG) -- PubChem CID: 9917980; Secoisolariciresinol diglucoside -- Obesity -- Brown/Beige adipocytes -- Thermogenesis -- AMPKα -- Mitochondria; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104852
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.