FRI391 A Metabolomics Analysis Of Moderate Energy Restriction In Healthy Lean Women

Abstract Disclosure: L. Levine: None. K. Overdahl: None. S. Molsberry: None. S. Shekhar: None. A. Jarmusch: None. J.E. Hall: None. Introduction: Metabolomics can elucidate metabolic responses to dietary interventions and has been used in energy restriction studies, primarily in overweight/obese men and women. Although the menstrual cycle affects the metabolome, most dietary intervention studies have not controlled for menstrual cycle phase, nor have they examined the effect of moderate, short-term energy restriction on the metabolic profile of healthy, normal-weight women. Objective: To characterize metabolomic changes in response to a 55% reduction in dietary intake during the early follicular phase of the menstrual cycle. Methods: Study participants included 19 healthy women aged 18-28 years who were of normal BMI and fitness, not restricting nutritional intake and with biochemically confirmed regular ovulatory menstrual cycles. Participants underwent 5-day dietary interventions in the early follicular phase of two menstrual cycles. The first diet consisted of neutral energy availability (NEA; 45 kcal/kg*lean body mass/day) and the second of deficient energy availability (DEA; 20 kcal/kg*lean body mass/day) without changes in macronutrient composition. On the 5th day of each diet, serum was collected at ∼8am following an overnight fast, and immediately before and every 10 minutes for 60 minutes after the consumption of a standardized isocaloric snack at ∼4pm. Untargeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectroscopy. Univariate statistics were performed on all metabolites, using t-tests with Benjamini-Hochberg false discovery rate adjusted p-values to account for multiple testing (p-value ≤ 0.05). Log2-fold change was calculated for all chemical features. Results: At baseline, participants had a weight of 61.9±2.75 kg (mean±SEM), BMI of 23.96±0.69 kg/m2 (mean±SEM), and percent body fat of 28.01±1.61% (mean±SEM). DEA resulted in a 1.25±0.13 kg (mean±SEM) decrease in body weight (p<0.01). While few statistically significant differences were present between fasted NEA and DEA samples, numerous chemical features were significantly upregulated in DEA post-snack samples. Specifically, 11 carnitines, 7 phosphocholines, and 8 fatty acids or fatty acid intermediates exhibited a log2fold change of 0.5 or higher (>40% increase; p ≤ 0.05) in post-snack DEA samples compared to NEA samples. Conclusion: These results strongly suggest that following isocaloric intake, moderate energy restriction in normal-weight, healthy women is associated not only with the use of fat as an energy source, but also with cellular membrane breakdown. Presentation: Friday, June 16, 2023