PP410 - EXPLORING THE METABOLIC SWITCHING THEORY OF INTERMITTENT FASTING IN HUMANS WITH OBESITY

PP410

EXPLORING THE METABOLIC SWITCHING THEORY OF INTERMITTENT FASTING IN HUMANS WITH OBESITY

K. Liu^1,2,*, X. T. Teong^1,2, A. D. Vincent^1,2, G. A. Wittert^1,2, B. Liu^1,2, A. T. Hutchison^1,2, L. K. Heilbronn^1,2

¹School of Medicine, Adelaide University, ²Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia

Rationale: In humans with obesity, we found equivalent weight loss yet greater improvements in glucose tolerance in the intermittent fasting plus early time restricted eating (iTRE) vs caloric restriction (CR). This sub-analysis explored metabolic profiles in iTRE (post-fasting and feeding days) vs CR.

Methods: An RCT was conducted in adults at elevated risk of diabetes (n=209, BMI 34.8±4.7kg/m²), with those from iTRE (30% energy requirements before 12pm with 20h fast on 3 days/week; usual diet on other days) and CR (70% energy requirements daily) included in this analysis. Fasting plasma glucose, insulin, non-esterified fatty acids (NEFA), triglycerides and polar metabolome were assessed after 12h fasts at baseline and month 6 (6A) for both groups, and again after 12h fast for CR or 20h fast for iTRE (6B). Between group effects at 6A and within group effects in iTRE (6A vs 6B) were examined by linear mixed model adjusted for baseline.

Results: Higher glucogenic amino acids, lactic acid and lower pentoses and sugar-derived acids (FDR<0.05) were found in iTRE vs CR after 12h fasts, with top enriched pathways related to glycolysis/gluconeogenesis, pyruvate metabolism and pentose phosphate pathway. The 20h fast induced reversals in these metabolites, and increased ketogenic amino acids, ketone bodies and citrate cycle intermediates (FDR<0.05), along with expected reductions in fasting glucose and insulin and increases in NEFA and triglycerides. Pathways related to amino acid degradation and biosynthesis, citrate cycle, and nicotinate/nicotinamide metabolism were further enriched post 20h fasting.

Conclusion: iTRE results in higher amino acid catabolism and suppressed carbohydrate oxidation vs CR. A switch from 12h to 20h fast reversed these processes alongside upregulated lipid-driven oxidative metabolism. Such metabolome shifts may reflect enhanced metabolic flexibility and contribute to the better glucose tolerance over CR.

Disclosure of Interest: None declared