Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD

Abstract Mitochondrial function is crucial for hepatic lipid metabolism. Current research identifies two types of mitochondria based on their contact with lipid droplets: peridroplet mitochondria (PDM) and cytoplasmic mitochondria (CM). This work aimed to investigate the alterations of CM and PDM in...

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Main Authors: Ye Xu, Yuan Zhang, Wen Sun, Qiang Tang, Wanyu Feng, Hongjian Xiao, Jingjie Wang, Xinmeng Yuan, Mengqi Xiang, Yaran Gao, Hanyu Zhang, Jiao Lu
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87871-2
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author Ye Xu
Yuan Zhang
Wen Sun
Qiang Tang
Wanyu Feng
Hongjian Xiao
Jingjie Wang
Xinmeng Yuan
Mengqi Xiang
Yaran Gao
Hanyu Zhang
Jiao Lu
author_facet Ye Xu
Yuan Zhang
Wen Sun
Qiang Tang
Wanyu Feng
Hongjian Xiao
Jingjie Wang
Xinmeng Yuan
Mengqi Xiang
Yaran Gao
Hanyu Zhang
Jiao Lu
author_sort Ye Xu
collection DOAJ
description Abstract Mitochondrial function is crucial for hepatic lipid metabolism. Current research identifies two types of mitochondria based on their contact with lipid droplets: peridroplet mitochondria (PDM) and cytoplasmic mitochondria (CM). This work aimed to investigate the alterations of CM and PDM in metabolic dysfunction-associated steatotic liver disease (MASLD) induced by spontaneous type-2 diabetes mellitus (T2DM) in db/db mice. It was found that insulin resistance increased both the number and size of lipid droplets in the liver by enhancing the accumulation of free fatty acids, which is accompanied by an increase in contacts with mitochondria. We described the different patterns of tight contacts between small lipid droplets and mitochondria in purified CM and PDM by examining their oxidation states and morphological characteristics. In CM, enhanced fatty acid oxidation resulted in elongated mitochondria that surrounded single small lipid droplets and were responsible for lipid droplet consumption, while in PDM, increased substrates for lipid synthesis promoted lipid droplet expansion with the assistance of the endoplasmic reticulum. These data show the different ways in which mitochondrial contact with lipid droplets could provide new insights for future research on liver lipid metabolism.
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spelling doaj-art-fd6ab79bf85243a5a00f31f4b12d776f2025-02-02T12:19:15ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87871-2Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLDYe Xu0Yuan Zhang1Wen Sun2Qiang Tang3Wanyu Feng4Hongjian Xiao5Jingjie Wang6Xinmeng Yuan7Mengqi Xiang8Yaran Gao9Hanyu Zhang10Jiao Lu11School of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteDepartment of General Surgery, Nanjing Maternity and Child Health Care Hospital, Womens Hospital of Nanjing Medical UniversitySchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteSchool of Sports and Health, Nanjing Sport InstituteAbstract Mitochondrial function is crucial for hepatic lipid metabolism. Current research identifies two types of mitochondria based on their contact with lipid droplets: peridroplet mitochondria (PDM) and cytoplasmic mitochondria (CM). This work aimed to investigate the alterations of CM and PDM in metabolic dysfunction-associated steatotic liver disease (MASLD) induced by spontaneous type-2 diabetes mellitus (T2DM) in db/db mice. It was found that insulin resistance increased both the number and size of lipid droplets in the liver by enhancing the accumulation of free fatty acids, which is accompanied by an increase in contacts with mitochondria. We described the different patterns of tight contacts between small lipid droplets and mitochondria in purified CM and PDM by examining their oxidation states and morphological characteristics. In CM, enhanced fatty acid oxidation resulted in elongated mitochondria that surrounded single small lipid droplets and were responsible for lipid droplet consumption, while in PDM, increased substrates for lipid synthesis promoted lipid droplet expansion with the assistance of the endoplasmic reticulum. These data show the different ways in which mitochondrial contact with lipid droplets could provide new insights for future research on liver lipid metabolism.https://doi.org/10.1038/s41598-025-87871-2Lipid droplets-mitochondria contactsCytoplasmic mitochondriaPeridroplet mitochondriaNonalcoholic fatty liver diseaseType-2 diabetes mellitusLipid metabolism
spellingShingle Ye Xu
Yuan Zhang
Wen Sun
Qiang Tang
Wanyu Feng
Hongjian Xiao
Jingjie Wang
Xinmeng Yuan
Mengqi Xiang
Yaran Gao
Hanyu Zhang
Jiao Lu
Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
Scientific Reports
Lipid droplets-mitochondria contacts
Cytoplasmic mitochondria
Peridroplet mitochondria
Nonalcoholic fatty liver disease
Type-2 diabetes mellitus
Lipid metabolism
title Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
title_full Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
title_fullStr Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
title_full_unstemmed Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
title_short Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD
title_sort characteristics of different lipid droplet mitochondrial contacts patterns during lipid droplet metabolism in t2dm induced masld
topic Lipid droplets-mitochondria contacts
Cytoplasmic mitochondria
Peridroplet mitochondria
Nonalcoholic fatty liver disease
Type-2 diabetes mellitus
Lipid metabolism
url https://doi.org/10.1038/s41598-025-87871-2
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