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

BackgroundPre-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 agains...

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Main Authors: Boju Sun, Misa Hayashi, Maya Kudo, Lili Wu, Lingling Qin, Ming Gao, Tonghua Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.627950/full
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author Boju Sun
Misa Hayashi
Maya Kudo
Lili Wu
Lingling Qin
Ming Gao
Ming Gao
Tonghua Liu
author_facet Boju Sun
Misa Hayashi
Maya Kudo
Lili Wu
Lingling Qin
Ming Gao
Ming Gao
Tonghua Liu
author_sort Boju Sun
collection DOAJ
description BackgroundPre-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.MethodsObese 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).ResultsThe 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.ConclusionsTaken 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.
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spelling doaj.art-c1fdb4d3ea8749ae9548e6c5e47e27b42022-12-21T22:11:47ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-03-011210.3389/fendo.2021.627950627950Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to ThermogenesisBoju Sun0Misa Hayashi1Maya Kudo2Lili Wu3Lingling Qin4Ming Gao5Ming Gao6Tonghua Liu7Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Pharmaceutical Sciences, Mukogawa Women’s University, Hyogo, JapanSchool of Pharmaceutical Sciences, Mukogawa Women’s University, Hyogo, JapanKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, ChinaTechnology Department, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Pharmaceutical Sciences, Mukogawa Women’s University, Hyogo, JapanInstitute for Biosciences, Mukogawa Women’s University, Hyogo, JapanKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, ChinaBackgroundPre-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.MethodsObese 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).ResultsThe 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.ConclusionsTaken 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.627950/fullmadecassosideobesityUCP-1SIRT1-AMPK signaling pathwaybrown fat
spellingShingle Boju Sun
Misa Hayashi
Maya Kudo
Lili Wu
Lingling Qin
Ming Gao
Ming Gao
Tonghua Liu
Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
Frontiers in Endocrinology
madecassoside
obesity
UCP-1
SIRT1-AMPK signaling pathway
brown fat
title Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
title_full Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
title_fullStr Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
title_full_unstemmed Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
title_short Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
title_sort madecassoside inhibits body weight gain via modulating sirt1 ampk signaling pathway and activating genes related to thermogenesis
topic madecassoside
obesity
UCP-1
SIRT1-AMPK signaling pathway
brown fat
url https://www.frontiersin.org/articles/10.3389/fendo.2021.627950/full
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