Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis.

Abstract

Background:

Pre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity.

Methods:

Obese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR).

Results:

The results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat.

Conclusions:

Taken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.

• Authors: Boju Sun, Misa Hayashi, Maya Kudo, Lili Wu, Lingling Qin, Ming Gao, Tonghua Liu
• Journal: Frontiers in endocrinology (Front Endocrinol (Lausanne)) Vol. 12 Pg. 627950 ( 2021) ISSN: 1664-2392 [Print] Switzerland
• PMID: 33767670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Sun, Hayashi, Kudo, Wu, Qin, Gao and Liu.

Chemical References

• Blood Glucose
• Carbohydrates
• Fatty Acids
• RNA, Messenger
• Triglycerides
• Triterpenes
• madecassoside
• Fatty Acid Synthases
• Aspartate Aminotransferases
• Alanine Transaminase
• AMP-Activated Protein Kinases
• Sirtuin 1

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adipose Tissue, Brown (drug effects, metabolism)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Blood Glucose (metabolism)
• Body Mass Index
• Carbohydrates
• Cerebral Cortex (drug effects, metabolism)
• Epididymis (drug effects, metabolism)
• Fatty Acid Synthases (genetics, metabolism)
• Fatty Acids (metabolism)
• Feeding Behavior (drug effects)
• Gene Expression Regulation (drug effects)
• Lipolysis (drug effects, genetics)
• Male
• Mesentery (metabolism)
• Mice
• Organ Size (drug effects)
• Oxidation-Reduction
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Thermogenesis (drug effects, genetics)
• Triglycerides (blood)
• Triterpenes (pharmacology)
• Weight Gain (drug effects, genetics)