Growth Differentiation Factor 15 Is Linked to Reduced Preference for Fatty Foods in Adults with Overweight or Obesity

Abstract

Abstract Objectives Growth differentiation factor 15 (GDF15) reduces food intake, dietary fat preference, and body weight in pre-clinical studies. Through recent human and in vitro studies, we have identified a role for GDF15 in the energy expenditure (exercise) side of the energy balance equation. Collectively, GDF15 has emerged as a novel candidate for the treatment of human obesity. However, whether GDF15 regulates food intake or food preference in humans remains to be elucidated. Herein, we hypothesized that fasting and exercise-induced GDF15 plasma concentrations would be related to habitual food intake and preference in adults with overweight/obesity. Methods Samples previously collected from eleven adults (age: 54 ± 3, BMI: 32.4 ± 1.6, kg/m2, six women, five men) were subjected to secondary analysis. Fasting plasma GDF15 was quantified by ELISA, while habitual diet was measured from 3-day dietary records. Dietary data was analyzed by the Dietary Analysis Core at Pennington Biomedical Research Center using FNDDS (USDA 2015–2016). A sub-cohort (n = 9) further completed a 7-day aerobic exercise training for 60 min/day at ∼85% HRmax, GDF15 assessment was repeated post-training. Results At baseline, GDF15 showed trends in reduced total energy intake (kcals, R = −0.40, P = 0.22), and was inversely associated with fatty foods (oils, g/day) (R = −0.62, P < 0.05), consistent with animal models. Exercise increased GDF15 in six adults (responders), but decreased in three adults (non-responders). Responders habitually consumed 52% less total fat (g/1000kcals, P = 0.01) and 59% less oils (g/1000kcals, P = 0.01) compared to non-responders. In agreement, exercise-induced changes in GDF15 negatively associated with baseline fat (kcal/g, R = −0.68, P < 0.05) and cheese (serving/kcal, R = −0.67, P < 0.05) intake. Conclusions This study provides preliminary evidence that GDF15 is linked to reduced fatty food preference in adults with overweight or obesity, suggesting a promising anti-obesity effect of GDF15 in humans. Larger human trials with repeated measurements are warranted to further elucidate the response. Funding Sources The study was supported by the National Institute of Health: UL1RR024989, U54GM104940, DK108089 (JPK) and T32AT004094 (JTM – trainee).