FRI007 Kisspeptin Does Not Affect Food Intake In Women With Overweight Or Obesity

Abstract

Abstract Disclosure: C. Izzi-Engbeaya: None. M. Choudhury: None. B. Patel: None. B. Muzi: None. A. Qayum: None. E.G. Mills: None. M. Ahsan: None. M. Phylactou: None. S. Clarke: None. L. Aslett: None. A.N. Comninos: None. A. Abbara: None. T. Tan: None. W.S. Dhillo: None. Background: Kisspeptin neurons in the hypothalamus are believed to play a role in mediating the interaction between metabolic and reproductive health. Functional neuroanatomical connections exist between kisspeptin neurons and appetite-regulating neurons in the arcuate nucleus of the hypothalamus. Female (but not male) global kisspeptin receptor knockout mice have reduced food intake compared to controls. However, studies of kisspeptin administration have yielded conflicting results, with either decreased, or unchanged food intake reported in rodent studies. Consistent with some of the literature, kisspeptin administration does not influence food intake in men. However, the effects of kisspeptin on food intake have not previously been studied in women. Research Question: What is the effect of kisspeptin administration on food intake in women? Methodology: A randomized controlled crossover study was performed in women with overweight or obesity (BMI >25 kg/m2) who were not in receipt of exogenous oral and/or transdermal estrogens or progestins. Each woman attended two study visits in random order following an overnight fast. During each study visit they received either a 2-hour intravenous infusion of kisspeptin-54 at a rate of 1.0 nmol/kg/hr, or a rate-matched vehicle infusion. The study was single-blinded, with participants unaware of the infusion identity. Participants were given an ad libitum meal 45 minutes after the start of each infusion. Blood samples were taken for reproductive and metabolic profiling, and visual analogue scales (VAS) to assess hunger were completed at regular intervals throughout both study visits. Data are presented as mean±SD. Results: 17 women (age 49±12 years, BMI 34±7 kg/m2) completed both study visits. As expected, LH levels were higher during kisspeptin than during vehicle infusion (p<0.01), confirming bioactivity of the kisspeptin dose. Pre-meal estradiol levels were similar during kisspeptin and vehicle infusions (p=0.34). There were no differences in pre-meal hunger VAS scores 30 mins after the start of the infusion (kisspeptin 5.2±2.7 vs vehicle 5.9±2.3, p=0.33) or bodyweight-adjusted food intake (kisspeptin 6.8±3.7 kcal/kg vs vehicle 6.2±2.8 kcal/kg, p=0.33). There were also no differences in glucose (p=0.97) or insulin (p=0.68) levels between kisspeptin and vehicle infusions. Conclusions: Acute intravenous administration of a biologically active dose of kisspeptin did not affect food intake or hunger in women with overweight or obesity. Furthermore, kisspeptin administration did not alter fasting or post-prandial glucose levels. This is the first study to examine the effects of kisspeptin on hunger and food intake in women and provides reassuring safety data for the ongoing development of kisspeptin-based therapeutics. Presentation: Friday, June 16, 2023