Anti-obesity action of INDUS810, a natural compound from Trigonella foenum-graecum: AMPK-dependent lipolysis effect in adipocytes
Journal
Obesity Research and Clinical Practice
Journal Volume
12
Journal Issue
6
Pages
562-569
Date Issued
2018
Author(s)
Abstract
Objective: We investigated the anti-obesity effect and underlying action mechanism of INDUS810 isolated from Trigonella foenum-graecum L. (Fabaceae), an annual herb commonly known as fenugreek and reported to have hypocholesterolemic, antidiabetic, anticancer and gastroprotective properties. Methods: For obese animal study, 4-week old mice were fed with normal diet or high-fat diet together with or without intraperitoneal injection of INDUS810 (200 mg/kg) twice per week for 15 weeks. 3T3-L1 cells were used to study action mechanism of INDUS810 in adipocyte differentiation and lipid metabolism. Results: We found that INDUS810 can reduce high-fat diet-induced weight increase in epididymal white adipose tissue, interscapular brown adipose tissue and liver, as well as serum levels of total cholesterol and low-density lipoprotein cholesterol. Moreover, the insulin sensitivity was significantly improved in INDUS810-treated obese mice. In 3T3-L1 adipocytes, we found that INDUS810 could inhibit lipid accumulation at either differentiating or mature stages, and increase lipolysis activity in mature adipocytes. Additionally, INDUS810 has no effects on cell viability nor the expressions of adipocyte differentiation markers like fatty acid synthase, peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α. In contrast, INDUS810 can increase protein levels of peroxisome proliferator-activated receptor α peroxisome-proliferator-activated receptor-γ co-activator 1β sirtuin 1 and sirtuin 3. Of note, INDUS810 can activate adenosine monophosphate-activated protein kinase, which leads to the reduction of lipid contents in adipocytes. Conclusion: Our in vitro and in vivo studies suggest that INDUS810 is a potential anti-obesity agent, and this action depends on activate adenosine monophosphate-activated protein kinase activation. ? 2018 Asia Oceania Association for the Study of Obesity
SDGs
Other Subjects
6,7 dihydro 4 hydroxy 3 (2' hydroxy 1,1' biphenyl 4 yl) 6 oxothieno[2,3 b]pyridine 5 carbonitrile; antiobesity agent; CCAAT enhancer binding protein alpha; cholesterol; fatty acid synthase; glucose; high density lipoprotein cholesterol; indus 810; low density lipoprotein cholesterol; natural product; peroxisome proliferator activated receptor gamma; peroxisome proliferator activated receptor gamma coactivator 1beta; protein kinase B; sirtuin 1; sirtuin 3; unclassified drug; wortmannin; adenylate kinase; antiobesity agent; insulin; plant extract; 3T3-L1 cell line; adipose tissue; AMPK signaling; animal cell; animal experiment; animal model; animal tissue; antidiabetic activity; antineoplastic activity; Article; body weight; body weight gain; caloric intake; cell differentiation; cell viability; cholesterol blood level; diet induced obesity; drug effect; drug mechanism; drug purity; fasting; fenugreek; glucose blood level; glucose level; glucose tolerance test; herbal medicine; high density lipoprotein cholesterol level; hypercholesterolemia; immunoblotting; in vivo study; insulin sensitivity; insulin tolerance test; interscapular brown adipose tissue; lipid degradation; lipid diet; lipid metabolism; lipid storage; lipolysis; liver; liver weight; low density lipoprotein cholesterol level; MAPK signaling; mouse; nonhuman; obesity; Pi3K/Akt signaling; priority journal; protein blood level; protein expression; protein phosphorylation; release assay; staining; stomach protection; white adipose tissue; adipocyte; adipogenesis; animal; blood; drug effect; insulin resistance; metabolism; obesity; physiology; Trigonella; 3T3-L1 Cells; Adenylate Kinase; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; Blood Glucose; Cell Differentiation; Insulin; Insulin Resistance; Lipid Metabolism; Lipolysis; Mice; Obesity; Plant Extracts; Trigonella
Publisher
Elsevier Ltd
Type
journal article