Intramuscular adipose tissue restricts functional muscle recovery

Summary: With age and disease, skeletal muscle is progressively lost and replaced by fibrotic scar and intramuscular adipose tissue (IMAT). While strongly correlated, it remains unclear whether IMAT has a functional impact on muscle. In the present study, we evaluated the impact of IMAT on muscle re...

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Main Authors: Alessandra M. Norris, Victoria R. Palzkill, Ambili B. Appu, Kiara E. Fierman, Christian D. Noble, Terence E. Ryan, Daniel Kopinke
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725007922
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author Alessandra M. Norris
Victoria R. Palzkill
Ambili B. Appu
Kiara E. Fierman
Christian D. Noble
Terence E. Ryan
Daniel Kopinke
author_facet Alessandra M. Norris
Victoria R. Palzkill
Ambili B. Appu
Kiara E. Fierman
Christian D. Noble
Terence E. Ryan
Daniel Kopinke
author_sort Alessandra M. Norris
collection DOAJ
description Summary: With age and disease, skeletal muscle is progressively lost and replaced by fibrotic scar and intramuscular adipose tissue (IMAT). While strongly correlated, it remains unclear whether IMAT has a functional impact on muscle. In the present study, we evaluated the impact of IMAT on muscle regeneration by creating a mouse model where the cellular origin of IMAT, fibro/adipogenic progenitors (FAPs), is prevented from differentiating into adipocytes (mFATBLOCK model). We found that blocking IMAT after an adipogenic injury allowed muscle to regenerate more efficiently, resulting in enhanced functional recovery. Our data explain why acute muscle injuries featuring IMAT infiltration, such as rotator cuff tears and acute denervation injuries, exhibit poor regeneration and lead to a loss of muscle function. It also demonstrates the therapeutic importance of preventing IMAT formation in acute injuries in order to maximize regeneration and minimize loss in muscle mass and function.
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spelling doaj-art-9926a7c8cdfd4f14a40887e200aad5922025-08-20T03:27:58ZengElsevierCell Reports2211-12472025-08-0144811602110.1016/j.celrep.2025.116021Intramuscular adipose tissue restricts functional muscle recoveryAlessandra M. Norris0Victoria R. Palzkill1Ambili B. Appu2Kiara E. Fierman3Christian D. Noble4Terence E. Ryan5Daniel Kopinke6University of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Applied Physiology and Kinesiology, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Applied Physiology and Kinesiology, Myology Institute, Gainesville, FL, USAUniversity of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USA; Corresponding authorSummary: With age and disease, skeletal muscle is progressively lost and replaced by fibrotic scar and intramuscular adipose tissue (IMAT). While strongly correlated, it remains unclear whether IMAT has a functional impact on muscle. In the present study, we evaluated the impact of IMAT on muscle regeneration by creating a mouse model where the cellular origin of IMAT, fibro/adipogenic progenitors (FAPs), is prevented from differentiating into adipocytes (mFATBLOCK model). We found that blocking IMAT after an adipogenic injury allowed muscle to regenerate more efficiently, resulting in enhanced functional recovery. Our data explain why acute muscle injuries featuring IMAT infiltration, such as rotator cuff tears and acute denervation injuries, exhibit poor regeneration and lead to a loss of muscle function. It also demonstrates the therapeutic importance of preventing IMAT formation in acute injuries in order to maximize regeneration and minimize loss in muscle mass and function.http://www.sciencedirect.com/science/article/pii/S2211124725007922CP: Metabolism
spellingShingle Alessandra M. Norris
Victoria R. Palzkill
Ambili B. Appu
Kiara E. Fierman
Christian D. Noble
Terence E. Ryan
Daniel Kopinke
Intramuscular adipose tissue restricts functional muscle recovery
Cell Reports
CP: Metabolism
title Intramuscular adipose tissue restricts functional muscle recovery
title_full Intramuscular adipose tissue restricts functional muscle recovery
title_fullStr Intramuscular adipose tissue restricts functional muscle recovery
title_full_unstemmed Intramuscular adipose tissue restricts functional muscle recovery
title_short Intramuscular adipose tissue restricts functional muscle recovery
title_sort intramuscular adipose tissue restricts functional muscle recovery
topic CP: Metabolism
url http://www.sciencedirect.com/science/article/pii/S2211124725007922
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