Exploring SCoR2: A Novel Target in MASLD and Obesity

SCoR2 is a protein denitrosylase that shifts cellular lipid programs from synthesis toward oxidation, identifying a potential therapeutic target for obesity and metabolic dysfunction-associated steatotic liver disease (MASLD).

Cellular mechanistic assays show target-specific denitrosylation by SCoR2. Measurements of S‑nitrosylation on transcriptional regulators and lipid biosynthetic enzymes — including mature SREBP1 and PPARγ regulators, FASN, and ACC — indicate that SCoR2’s denitrosylase activity restores processing and function of these factors. In cells, changes in S‑nitrosylation paralleled altered expression of lipogenic genes and reductions in lipid synthesis rates, supporting direct mechanistic control of lipid accrual by SCoR2-mediated denitrosylation.

In animal models, genetic deletion or small-molecule SCoR2 inhibition reduced adipose mass and improved metabolic markers. Reported phenotypes include resistance to diet‑induced weight gain, increased hepatic fatty acid oxidation, and lower triglyceride content in liver and adipose tissue. Reproducible protection against steatosis alongside higher energy expenditure reinforces SCoR2 as a tractable preclinical target.

Clinical correlations from patient samples associate higher SCoR2 expression with larger adipocyte size and greater hepatic steatosis, linking elevated activity to more severe lipid accumulation. Assays of SCoR2 expression or activity could therefore help stratify disease severity or monitor therapeutic response, but prospective validation in independent cohorts and standardization of activity assays are required as the next essential steps.