Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 322, Issue 4, Pages E331-E343Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00255.2021
Keywords
Cidea; Cidec; diabetes; fat metabolism; lipid droplets; lipids; obesity
Categories
Funding
- National Institutes of Health (NIH) [RO1DK101711, RO1HL140836, RO1DK124126]
- Osteopathic Heritage Foundation's Vision 2020 to Heritage college of Osteopathic medicine at Ohio University
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This study identifies Fsp27 as a novel protein associated with muscle metabolism. The Fsp27-knockout model reveals that Fsp27 plays a role in muscular-fat storage, muscle endurance, and muscle strength, ultimately impacting limb movement. Additionally, the study suggests a potential metabolic paradox in which Fsp27-knockout mice, presumed to be metabolically healthy based on glucose utilization and oxidative metabolism, exhibit impaired exercise capacity and muscular performance.
Fsp27 was previously identified as a lipid droplet-associated protein in adipocytes. Various studies have shown that it plays a role in the regulation of lipid homeostasis in adipose tissue and liver. However, its function in muscle, which also accumulate and metabolize fat, remains completely unknown. Our present study identifies a novel role of Fsp27 in muscle performance. Here, we demonstrate that Fsp27-/- and Fsp27+ /- mice, both males and females, had severely impaired muscle endurance and exercise capacity compared with wild-type controls. Liver and muscle glycogen stores were similar among all groups fed or fasted, and before or after exercise. Reduced muscle performance in Fsp27-/- and Fsp27+ /- mice was associated with severely decreased fat content in the muscle. Furthermore, results in heterozygous Fsp27+ /- mice indicate that Fsp27 haploinsufficiency undermines muscle performance in both males and females. In summary, our physiological findings reveal that Fsp27 plays a critical role in muscular fat storage, muscle endurance, and muscle strength. NEW & NOTEWORTHY This is the first study identifying Fsp27 as a novel protein associated with muscle metabolism. The Fsp27-knockout model shows that Fsp27 plays a role in muscular-fat storage, muscle endurance, and muscle strength, which ultimately impacts limb movement. In addition, our study suggests a potential metabolic paradox in which FSP27-knockout mice presumed to be metabolically healthy based on glucose utilization and oxidative metabolism are unhealthy in terms of exercise capacity and muscular performance.
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