Sln, also known as sarcolipin, is a key regulator in human skeletal muscle cells. It uncouples sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA), increasing ATP consumption and contributing to heat liberation. This thermogenic mechanism in skeletal muscle has potential implications for counteracting obesity and associated metabolic disorders [1].

In a study generating human skeletal muscle cells with stable Sln knockdown (SLN-KD), it was found that depletion of Sln did not influence cell viability. However, glucose and oleic acid (OA) oxidation were diminished in SLN-KD cells compared to control myotubes. Basal respiration was also reduced. The metabolic perturbation was reflected by reduced gene expression levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and forkhead box O1 (FOXO1). Additionally, OA accumulation, lipid formation, and incorporation of OA into complex lipids increased in SLN-KD cells. De novo lipogenesis and lipid droplet accumulation were also enhanced [1].

In conclusion, Sln is crucial for maintaining metabolic homeostasis in human skeletal muscle. Findings from Sln-KD models suggest that Sln-mediated futile cycling of SERCA could be a significant therapeutic strategy for obesity and associated metabolic disorders. These models help us understand the role of Sln in metabolic regulation and offer potential directions for treating related diseases.

References:

1. Mengeste, Abel M, Katare, Parmeshwar, Dalmao Fernandez, Andrea, Thoresen, G Hege, Kase, Eili Tranheim. 2022. Knockdown of sarcolipin (SLN) impairs substrate utilization in human skeletal muscle cells. In Molecular biology reports, 49, 6005-6017. doi:10.1007/s11033-022-07387-0. https://pubmed.ncbi.nlm.nih.gov/35364719/