Exercise Intensity, Insulin Sensitivity and Sex, but not Obesity, Impact Ghrelin and Appetite Responses to Acute Exercise

Background: The hormone ghrelin has 2 isoforms, acylated (AG) and deacylated (DAG), and has biological effects that include energy balance, appetite, and glucose homeostasis. Ghrelin dysregulation is common in adults with obesity and/or diabetes and exercise has been shown to influence its release. However, the relationship between obesity, insulin sensitivity status (IS), and appetite is understudied, especially in females. Thus, the purpose of this study was to investigate the effects of obesity (BMI≥30), IS (Matsuda Index > 4.3), and ghrelin (TG, AG, DAG) on appetite after acute exercise of differing intensity. HYPOTHESES: We hypothesized that high intensity exercise and obesity status would lead to a suppression of appetite and decreases in all ghrelin isoforms. Methods: Seventeen lean adults (11IS/9F; Age: 41.2.0±9.2 y.; BMI: 22.2±1.7 kg/m 2 ; VO 2peak : 32.5±6.3 ml/kg/min) and eleven adults with obesity (3IS/7F; Age: 35.1±11.2 y.; BMI: 32.2±2.6 kg/m 2 ; VO 2peak : 21.5±3.9 ml/kg/min) underwent maximal exercise testing on a cycle ergometer. The lactate threshold (LT) and VO 2peak from maximal testing were used to determine intensities for randomized, calorically matched exercise conditions – moderate intensity (MOD): power output at LT; high intensity (HIGH): power output at 75% of difference between VO 2peak and LT; and control (CON): rest. Plasma glucose and insulin values during an oral glucose tolerance test were used to determine IS via the Matsuda Index. Plasma blood samples were obtained from an indwelling catheter at baseline at 60, 90, 120, 150, and 180 mins during experimental visits and used to measure total ghrelin (TG), AG, and DAG. At the same timepoints, participants also completed a visual analog scale (VAS) to assess desired to eat (EAT), hunger (HUN), fullness (FULL), satisfaction (SAT), and appetite (APP). APP scores were calculated with the formula: APP = EAT + HUN + (100 – FULL) + (100 – SAT))/4. Total area under the curve (AUC) was calculated for AG, DAG, TG, and VAS variables using the trapezoidal method. Linear mixed models were used to determine the appetite response to exercise, with participant as the random factor and obesity status, IS, sex, and condition as fixed factors. F-tests of nested models were used to determine differences in fixed effects. Estimated marginal means were utilized to estimate the means that were adjusted for the factors in each model. Data are reported as mean ± SE. Results: For ghrelin, there was a main effect of condition in AG AUC and TG AUC models, with reduced levels in HIGH v. MOD ( p =0.017-0.033) and a main effect of IS, where participants with insulin resistance had reduced levels of AG AUC regardless of condition( p =0.033). There was also a main effect of condition in APP AUC (HIGH < MOD; p =0.017) and an interaction between condition and sex where females had suppressed APP AUC in HIGH v. MOD ( p =0.02) and CON ( p <0.001). There were no effects found in males or based on obesity status ( p >0.05). Conclusions: Ghrelin and appetite are suppressed with high intensity exercise, with sex and insulin sensitivity status impacting this response. Future research should investigate if short-to-long-term high intensity exercise interventions elicit consistently suppressed ghrelin and appetite in untrained adults. UVA School of Education and Human Development and NIH NIDDK (R01 DK129510). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.