PT  - JOURNAL ARTICLE
AU  - Luis Rodrigo Cataldo
AU  - Rodrigo Fernández-Verdejo
AU  - José Luis Santos
AU  - Jose Eduardo Galgani
TI  - Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals
AID  - 10.1136/jim-2017-000681
DP  - 2018 Mar 27
TA  - Journal of Investigative Medicine
PG  - jim-2017-000681
4099  - http://hw-f5-jim.highwire.org/content/early/2018/03/27/jim-2017-000681.short
4100  - http://hw-f5-jim.highwire.org/content/early/2018/03/27/jim-2017-000681.full
AB  - Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that attenuates weight gain and hyperinsulinemia when administered to high fat-fed mice. MOTS-c is therefore a potential regulator of metabolic homeostasis under conditions of high-energy supply. However, the effect of insulin resistance and obesity on plasma MOTS-c concentration in humans is unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c concentration and analyzed its relationship with insulin sensitivity surrogates, in lean and obese humans (n=10 per group). Obese individuals had impaired insulin sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and obese individuals (0.48±0.16 and 0.52±0.15 ng/mL; p=0.60), it was correlated with HOMA (r=0.53; p<0.05) and Matsuda index (r=−0.46; p<0.05). Notably, when the groups were analyzed separately, the associations remained only in lean individuals. We conclude that plasma MOTS-c concentration is unaltered in human obesity. However, MOTS-c associates positively with insulin resistance mostly in lean individuals, indicating that plasma MOTS-c concentration depends on the metabolic status in this population. Such dependence seems altered when obesity settles. The implications of plasma MOTS-c for human metabolic homeostasis deserve future examination.