Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice

Abstract Skeletal muscle atrophy is a complication of obesity, partially induced by impaired mitophagy. This study investigates whether Berberine(BBR) protects mice from obese skeletal muscle atrophy and the underlying molecular mechanism. Twenty C57BL/6 mice were fed a high-fat diet until they weig...

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Main Authors: Yijie Wu, Yanhui Yang, Caixia Du, Xiaoyue Peng, Wenying Fan, Baocheng Chang, Chunyan Shan
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-89297-2
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author Yijie Wu
Yanhui Yang
Caixia Du
Xiaoyue Peng
Wenying Fan
Baocheng Chang
Chunyan Shan
author_facet Yijie Wu
Yanhui Yang
Caixia Du
Xiaoyue Peng
Wenying Fan
Baocheng Chang
Chunyan Shan
author_sort Yijie Wu
collection DOAJ
description Abstract Skeletal muscle atrophy is a complication of obesity, partially induced by impaired mitophagy. This study investigates whether Berberine(BBR) protects mice from obese skeletal muscle atrophy and the underlying molecular mechanism. Twenty C57BL/6 mice were fed a high-fat diet until they weighed more than 20% of the average body weight of the control group. The mice were then divided into two groups and gavaged with BBR or vehicle for 8 weeks. 10 mice were used as controls. Fasting blood glucose was measured, an oral glucose tolerance test was performed, and the mice were measured for grip strength and exercise capacity. H&E and Oil Red O staining were used to observe the pathological changes of skeletal muscle. MURF1, FBXO32, BAX, BCL2, P62, LC3 and mitophagy receptor FUNDC1 were observed in mice. BBR was intervened in C2C12 myotubes. The role of FUNDC1 was verified by RNA interference. We found that BBR treatment increased grip strength and improved muscle function. BBR not only reduced weight gain, excessive lipid accumulation and hyperlipidemia, but also ameliorated obesity-induced skeletal muscle atrophy and apoptosis. BBR promoted autophagy and increased FUNDC1 protein expression. The same positive effects were observed after BBR intervening on C2C12 myotubes, whereas FUNDC1 RNA interference attenuated the anti-skeletal muscle atrophy effect of BBR. These results suggest that BBR ameliorated obesity-induced skeletal muscle atrophy in mice by modulating the skeletal muscle mitophagy receptor FUNDC1, which may be a potential therapeutic target for obesity-induced skeletal muscle atrophy.
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spelling doaj-art-2d88465d05ab47be9bdf76fbd603346f2025-08-20T03:00:58ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-89297-2Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of miceYijie Wu0Yanhui Yang1Caixia Du2Xiaoyue Peng3Wenying Fan4Baocheng Chang5Chunyan Shan6NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyAbstract Skeletal muscle atrophy is a complication of obesity, partially induced by impaired mitophagy. This study investigates whether Berberine(BBR) protects mice from obese skeletal muscle atrophy and the underlying molecular mechanism. Twenty C57BL/6 mice were fed a high-fat diet until they weighed more than 20% of the average body weight of the control group. The mice were then divided into two groups and gavaged with BBR or vehicle for 8 weeks. 10 mice were used as controls. Fasting blood glucose was measured, an oral glucose tolerance test was performed, and the mice were measured for grip strength and exercise capacity. H&E and Oil Red O staining were used to observe the pathological changes of skeletal muscle. MURF1, FBXO32, BAX, BCL2, P62, LC3 and mitophagy receptor FUNDC1 were observed in mice. BBR was intervened in C2C12 myotubes. The role of FUNDC1 was verified by RNA interference. We found that BBR treatment increased grip strength and improved muscle function. BBR not only reduced weight gain, excessive lipid accumulation and hyperlipidemia, but also ameliorated obesity-induced skeletal muscle atrophy and apoptosis. BBR promoted autophagy and increased FUNDC1 protein expression. The same positive effects were observed after BBR intervening on C2C12 myotubes, whereas FUNDC1 RNA interference attenuated the anti-skeletal muscle atrophy effect of BBR. These results suggest that BBR ameliorated obesity-induced skeletal muscle atrophy in mice by modulating the skeletal muscle mitophagy receptor FUNDC1, which may be a potential therapeutic target for obesity-induced skeletal muscle atrophy.https://doi.org/10.1038/s41598-025-89297-2Obesity-induced skeletal muscle atrophyBerberineMitophagyFUNDC1
spellingShingle Yijie Wu
Yanhui Yang
Caixia Du
Xiaoyue Peng
Wenying Fan
Baocheng Chang
Chunyan Shan
Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
Scientific Reports
Obesity-induced skeletal muscle atrophy
Berberine
Mitophagy
FUNDC1
title Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
title_full Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
title_fullStr Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
title_full_unstemmed Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
title_short Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice
title_sort berberine attenuates obesity induced skeletal muscle atrophy via regulation of fundc1 in skeletal muscle of mice
topic Obesity-induced skeletal muscle atrophy
Berberine
Mitophagy
FUNDC1
url https://doi.org/10.1038/s41598-025-89297-2
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