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Objective: Polycystic 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. Methods: All subjects underwent 5-hour intralipid/saline infusion with a hyperinsulinemic-euglycaemic clamp in the final 2 hours. Plasma samples were collected to measure circulating MOTS-c using a commercial ELISA kit. Subsequently, this was repeated following an eight-week exercise intervention. Results: Intralipid 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 232±124% 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. Conclusions In 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.

Background Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. Results Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. Conclusions Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.