Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance
Du C, Zhang C, Wu W, Liang Y, Wang A, Wu S, Zhao Y, Hou L, +2 more
Pediatric Diabetes (2018) · n=97
Circulating MOTS-c was significantly lower in obese male Chinese children and adolescents than in normal-weight controls and correlated inversely with HOMA-IR — the first paediatric demonstration of the mitochondrial-derived-peptide-and-insulin-resistance association predicted by Lee 2015.
This 2018 Pediatric Diabetes paper from Wuhan Tongji Hospital is one of the earliest human-cohort confirmations that circulating MOTS-c levels track inversely with insulin resistance — and the first such demonstration in a paediatric population. The investigators enrolled 97 children and adolescents (40 with obesity, 57 normal-weight controls) and measured fasting plasma MOTS-c, HOMA-IR, lipid panel, and anthropometric measures. Circulating MOTS-c was significantly decreased in the obese subgroup, but the difference was driven entirely by male participants — among obese boys, MOTS-c was substantially lower than in normal-weight boys and correlated inversely with HOMA-IR, fasting insulin, waist circumference, and triglycerides. Female obesity status was not associated with significant MOTS-c differences in the cohort, an unexpected sex-difference finding. The paper aligns with the broader Lee 2015 mouse-model framing — exogenous MOTS-c prevented diet-induced insulin resistance, and endogenous levels track inversely with the obesity-and-insulin-resistance phenotype — and contributes to the human-correlational evidence base from which MOTS-c-as-metabolic-biomarker discussions have emerged.
This is a cross-sectional cohort study, not an interventional trial — the inverse correlation between MOTS-c and insulin-resistance markers does not establish causal direction. The 97-patient sample is small for the male-female stratification the paper reports, and the sex-difference finding (significant in boys, not in girls) has not been independently replicated to a degree that would settle it. The cohort is Chinese paediatric, which may not generalise to other ethnic populations or to adult metabolic disease. The MOTS-c ELISA used to measure circulating levels has known cross-reactivity and standardisation issues across publications in this literature — the absolute values reported across human-cohort papers are not directly comparable. As with the rest of the human MOTS-c evidence, the correlation does not justify exogenous MOTS-c administration in metabolic disease without interventional data, which does not yet exist.
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