Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.

ObjectivePolycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS-c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK-dependent pathways. The current study was designed to examine the response of MOTS-c to lipids (intralipid) followed by insulin in PCOS and healthy subjects. MethodsAll subjects underwent 5-hour intralipid/saline infusion with a hyperinsulinemic-euglycaemic clamp in the final 2hours. Plasma samples were collected to measure circulating MOTS-c using a commercial ELISA kit. Subsequently, this was repeated following an eight-week exercise intervention. ResultsIntralipid significantly increased plasma MOTS-c both in controls and PCOS subjects, whilst the insulin infusion blunted the intralipid-induced response seen for both lipids and MOT-c. Intralipid elevated plasma MOTS-c to 232124% of basal in control (P<0.01) and to 349 +/- 206% of basal in PCOS (P<0.001) subjects. Administration of insulin suppressed intralipid-induced MOTS-c from 232 +/- 124% to 165 +/- 97% (NS) in control and from 349 +/- 206% to 183 +/- 177% (P<0.05) in PCOS subjects, respectively. Following exercise, intralipid elevated plasma MOTS-c to 305 +/- 153% of basal in control (P<0.01) and to 215 +/- 103% of basal in PCOS (P<0.01) subjects; insulin suppressed intralipid-induced MOTS-c only in controls. ConclusionsIn conclusion, this is the first study to show increased lipid enhanced circulating MOTS-c whilst insulin attenuated the MOTS-c response in human. Further, eight weeks of moderate exercise training did not show any changes in circulating MOTS-c levels in healthy controls and in women with PCOS.