Kisspeptin does not have detrimental metabolic effects in women

Chioma  Izzi-Engbeaya; Muhammad Choudhury; Bijal Patel; Beatrice Muzi; Ambreen Qayum; Edouard G Mills; Maheen Ahsan; Maria Phylactou; Sophie Clarke; Laura Aslett; Alexander Comninos; Ali Abbara; Tricia Tan; Waljit Dhillo

doi:10.1530/endoabs.90.RC10.4

Background: There is emerging evidence that kisspeptin, a hormone with well-established reproductive effects, may also have important metabolic effects. Acute kisspeptin administration enhances insulin secretion under hyperglycaemic conditions in male rodents and men, and kisspeptin receptor agonism improves steatohepatits in male mice in a rodent model of non-alcoholic fatty liver disease. However, the metabolic effects of kisspeptin may exhibit sexual dimorphism as female (but not male) kisspeptin receptor knockout mice have reduced food intake. Kisspeptin administration has been shown to have no effect on food intake in men, but the effect of kisspeptin on food intake in women has not been investigated.

Methods: We performed a single-blinded randomized controlled crossover study in women with overweight or obesity (BMI >25 kg/m²) who had not received exogenous estrogens or progestins in the preceding 3 months. Each woman attended two study visits (in random order) following a 14-hour fast. During each study visit either an intravenous infusion of kisspeptin-54 at a rate of 1.0 nmol/kg/hr, or a rate-matched vehicle infusion, were administered for 120 minutes. At regular intervals during the study visits, blood samples were taken. Participants completed visual analogue scales (VAS) to assess hunger prior to the start of the infusions, 30 minutes after the start of the infusions (pre-meal) and 75 minutes after the start of the infusion (post-meal). Forty-five minutes after the start of each infusion, the women were given an ad libitum meal. All data are presented as mean±SD.

Results: Seventeen women (BMI 34±7 kg/m², n=12 with BMI >30 kg/m²) completed both study visits. Kisspeptin administration increased LH levels (P<0.01), consistent with its known reproductive effects. However, pre-meal estradiol levels were unaffected by kisspeptin administration (P=0.34). Kisspeptin administration did not affect appetite pre-meal (hunger VAS scores at 30 mins: kisspeptin 5.2±2.7 vs vehicle 5.9±2.3, P=0.33) nor post-meal (hunger VAS scores at 75 mins: kisspeptin 0.5±1.0 vs vehicle 0.4±0.6, P=0.87). Food intake was similar during kisspeptin and vehicle infusions (kisspeptin 604±267 kcal vs vehicle 560±217 kcal, P=0.41). Glucose (P=0.97) and insulin (P=0.68) levels were similar during the infusions.

Conclusions: This is the first study to investigate the metabolic effects of kisspeptin in women. Similar to findings in men with BMI <25 kg/m², acute administration of a pharmacologically active dose of kisspeptin to women with BMI >25 kg/m² did not affect appetite or food intake. These data provide reassurance that kisspeptin receptor agonism is unlikely to have undesirable orexigenic effects in humans.

Endocrine Abstracts

RC10.4