Dataset Information

Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

ABSTRACT:

Unlabelled

: Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipose depots, it likely affects tissue function outside its boundaries. Therefore, we characterized the epimuscular (EM) fat depot of the human rotator cuff, defined its response to RC tears, and evaluated its influence on myogenesis in vitro. EM fat biopsies exhibited morphological and functional features of human beige fat compared with patient-matched s.c. biopsies, which appeared whiter. The transcriptional profile of EM fat and isolated EM adipose-derived stem cells (ASCs) shifted as a function of the tear state; EM fat from intact cuffs had significantly elevated expression of the genes associated with uncoupled respiration, and the EM fat from torn cuffs had increased expression of beige-selective genes. EM ASC cocultures with human- and mouse-derived myogenic cells exhibited increased levels of myogenesis compared with s.c. cultures. Increased fusion and decreased proliferation of myogenic cells, rather than changes to the ASCs, were found to underlie this effect. Taken together, these data suggest that EM fat in the human rotator cuff is a novel beige adipose depot influenced by cuff state with therapeutic potential for promoting myogenesis in neighboring musculature.

Significance

Rotator cuff tears affect millions of people in the U.S.; however, current interventions are hindered by persistent muscle degeneration. This study identifies the therapeutic potential for muscle recovery in the epimuscular fat in the rotator cuff, previously considered a negative feature of the pathology, and finds that this fat is beige, rather than white. This is important for two reasons. First, the stem cells that were isolated from this beige fat are more myogenic than those from white fat, which have been the focus of stem cell-based therapies to date, suggesting epimuscular fat could be a better stem cell source to augment rotator cuff repair. Second, these beige stem cells promote myogenesis in neighboring cells in culture, suggesting the potential for this fat to be manipulated therapeutically to promote muscle recovery through secreted signals.

SUBMITTER: Meyer GA

PROVIDER: S-EPMC4479624 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

Meyer Gretchen A GA Gibbons Michael C MC Sato Eugene E Lane John G JG Ward Samuel R SR Engler Adam J AJ

Stem cells translational medicine 20150521 7

<h4>Unlabelled</h4>: Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipose depots, it likely affects tissue function outside its boundaries. Therefore, we characterized the epimuscular (EM) fat depot of the human rotator cuff, defined its respo ...[more]

PMID: 25999520

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Project description:Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis.

Project description:Purpose To compare patient-reported and surgical outcome measures in patients with and without secondary shoulder stiffness (SSS) undergoing rotator cuff repair (RCR). Methods Patients undergoing rotator cuff repair from 2014 to 2020 with complete patient-reported outcome measures (PROMs) by the short-form 12 survey (SF-12) were retrospectively reviewed to identify if operative intervention for SSS was performed alongside the RCR. Those patients with operative intervention for SSS were propensity matched to a group without prior intervention for stiffness by age, sex, laterality, body mass index, diabetes mellitus status, and the presence of a thyroid disorder. The groups were compared by rotator cuff tear (RCT) size, surgical outcomes, further surgical intervention, rotator cuff retear rate, postoperative range of motion (ROM), and SF-12 results at 1 year after surgery. Delta values were calculated for component scores of the SF-12 and ROM values by subtracting the preoperative result from the postoperative result. Results A total of 89 patients with SSS were compared to 156 patients in the control group at final analysis. The patients in the SSS group experienced a significant improvement in the delta mental health component score (MCS-12) of the SF-12 survey that was not seen in the control group (P = .005 to P = .539). Both groups experienced significant improvement by the delta physical health component score (PCS-12) of the SF-12 survey (SSS: 7.68; P < .001; control: 6.95; P < .001). The SSS group also experienced greater improvement of their forward flexion (25.8° vs 12.9°; P = .005) and external rotation (7.13° vs 1.65°; P = .031) ROM than the control group. Conclusions Operative intervention of SSS at the time of RCR has equivalent postoperative SF-12 survey outcome scores when compared to patients undergoing RCR without preoperative stiffness despite those patients having lower preoperative scores. Level of Evidence Level III retrospective comparative study.

Dataset Information

Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

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Significance

Publications

Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

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