Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis

MacPherson, Rebecca E. K.; Peters, Sandra J.

doi:10.1139/apnm-2014-0485

Cited by 43 publications

(35 citation statements)

References 99 publications

(226 reference statements)

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“…There was a down-regulation in nearly all of the genes responsible for the transport of FFAs into the muscle cells, and the synthesis of TGs from FFAs (53), including CD36, ACSL1, ACSL6, AGPAT9/glycerol-3-phosphate acyltransferase 3, glycerol-3-phosphate acyltransferase 1, mitochondrial, AGPAT1, AGPAT3, AGPAT6, lipin 1-3, and DGAT1-2. PLIN2, which coats lipid droplets and appears to be important for lipid droplet growth and stability (54), was also up-regulated after rotator cuff tear, whereas PLIN5, which also coats lipid droplets but also helps to target fatty acids to mitochondria for oxidation (54), was down-regulated. Consistent with these findings, genes involved with hydrolyzing TG stored in lipid droplets in fatty acids (53,55) were down-regulated after injury, including ATGL and PNPLA3, hormone-sensitive lipase, and monoglyceride lipase.…”

Section: Discussionmentioning

confidence: 99%

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

et al. 2019

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Myosteatosis is the pathologic accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated that the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathologic changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study because the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls or 10, 30, or 60 d after injury and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics, and proteomics, along with bioinformatics techniques to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.—Gumucio, J. P., Qasawa, A. H., Ferrara, P. J., Malik, A. N., Funai, K., McDonagh, B., Mendias, C. L. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis. FASEB J. 33, 7863–7881 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

et al. 2019

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“…FFAs (48), including CD36, ACSL1, ACSL6, AGPAT9/GPAT3, GPAM, AGPAT1, AGPAT3, AGPAT6, lipin 1-3, and DGAT1-2. Perilipin 2, which coats lipid droplets and appears to be important for lipid droplet growth and stability (49) was also upregulated after rotator cuff tear, while perilipin 5 which also coats lipid droplets but also helps to target fatty acids to mitochondria for oxidation (49), was downregulated. Consistent with these findings, genes involved with hydrolyzing triglyceride stored in lipid droplets into fatty acids (48,50) were downregulated after injury, including ATGL and PNPLA3, hormone sensitive lipase, and monoglyceride lipase.…”

Section: Discussionmentioning

confidence: 99%

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Gumucio

Qasawa

Ferrara

et al. 2018

Preprint

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Myosteatosis is the pathological accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathological changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study, as the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls, or 10, 30, or 60 days after injury, and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics and proteomics, along with bioinformatics techniques, to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings, and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.

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“…Each PLIN family member likely performs a unique function in the regulation of lipid droplet dynamics [35], and PLIN1 plays a "switch" role in regulating lipolysis. Native PLIN1 may serve as a barrier, protecting droplet triglycerides from basal lipolysis, whereas phosphorylated PLIN1 could indirectly activate ATGL [36,37]. Previous studies have found that the expression of PLIN1 was higher in muscles with high IMF contents [34,38].…”

Section: Ppar Pathway Regulates Weakened Lipolysis and Enhanced Lipogmentioning

confidence: 98%

Effect of Divergent Selection for Intramuscular Fat Content on Muscle Lipid Metabolism in Chickens

Liu

Cui

Xing

et al. 2019

Animals

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Simple Summary: Intramuscular fat is an important factor affecting meat quality and consumer acceptance. Appropriate increases in the intramuscular fat content contribute to the improvement of meat quality, and genetic selection is an effective method to increase the intramuscular fat content in chickens. In this study, chicken lines divergently selected for their intramuscular fat content were used to investigate the mechanisms behind differential intramuscular fat deposition. These results found in this study may contribute to the improvement of meat quality in chickens.Abstract: Intramuscular fat (IMF)-an important factor affecting meat quality-can be appropriately increased by genetic selection. Chicken lines divergently selected for IMF content were used in this study to investigate the mechanisms behind differential IMF deposition. Sixty 15th generation chickens were genotyped using the IASCHICK 55K single nucleotide polymorphism (SNP) chip. After quality control, 59 chickens and 36,893 SNPs were available for subsequent analysis. Population structure assessment indicated that the lines were genetically differentiated. Based on the top 1% paired fixation index values, three pathways were significantly (p < 0.05) enriched, and nine genes were considered candidate genes for differential IMF deposition. Differences between the lines in the expressions of representative genes involved in the above pathways were detected in 16th generation chickens. This study suggests that genetic selection for increased IMF in the pectoralis major muscle may enhance fatty acid synthesis, transport, and esterification, and reduce triglyceride hydrolysis. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, glycerolipid metabolism, and fatty acid degradation pathway may have contributed to the differences in IMF deposition between the lines. These results contribute to the understanding of the genetic mechanisms behind IMF deposition, and the improvement of chicken meat quality.

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Piecing together the puzzle of perilipin proteins and skeletal muscle lipolysis

Cited by 43 publications

References 99 publications

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Effect of Divergent Selection for Intramuscular Fat Content on Muscle Lipid Metabolism in Chickens

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