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Study wrapper · #736

Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss.

Yoon SH, Yuan F, Zhu X, et al. Journal of clinical & translational endocrinology. 2026.
MixedOtherMentions: MOTS-c

Editor's note

This exploratory human study reports that circulating MOTS-c was higher in adults with obesity than lean controls (273 vs 223 pg/mL), with BMI and insulin resistance independently predicting elevated levels and a nonlinear, biphasic relationship with HOMA-IR. In 10 patients followed after bariatric surgery, MOTS-c did not change despite major weight loss, and adipose-tissue MOTS-c neither differed by group nor tracked with blood levels. The authors frame elevated MOTS-c as a possible compensatory response. This is a small, cross-sectional-plus-brief-longitudinal observational study; associations cannot establish causation. It usefully complicates the MOTS-c picture: contrast with reports of reduced MOTS-c in PCOS and other states shows the direction is context-dependent. Weight it as hypothesis-generating and explicitly awaiting larger validation.

Plain-language abstract

MOTS-c is a mitochondria-derived peptide involved in how the body handles sugar and fat. Researchers compared blood MOTS-c in 32 adults with obesity (scheduled for weight-loss surgery) and 22 lean adults. MOTS-c was higher in the obesity group, and both body mass index and insulin resistance independently predicted higher levels; the relationship with insulin resistance was not a straight line but rose sharply past a certain point. In 10 people re-tested six months after surgery, MOTS-c stayed the same even though they had lost significant weight. MOTS-c in fat tissue did not differ between groups or match blood levels. The authors suggest higher MOTS-c may be a compensating response to metabolic stress rather than a cause. Because this looked mainly at one time point in a small sample, it cannot prove cause and effect, and it points in the opposite direction to some other conditions where MOTS-c is lower. Larger studies are needed to confirm.