Oleoylethanolamine precursor triggers lipolysis during Time-Restricted Intermittent Fasting and promotes longevity and healthy aging of Caenorhabditis elegans.

Intermittent fasting (IF), Time-Restricted Intermittent Fasting (TRIF), and fasting-mimicking diets have gained popularity among weight loss programs. The body efficiently utilizes its energy reserves to activate metabolic processes in response to food intake. Modifying food regimens can alter/extend life span and promote healthy aging by activating specific metabolic processes. However, changes in general lipid metabolism, especially the alteration in N-acylethanolamide (NAE) regulation and their role in promoting lipolysis and extending life span during TRIF, are still inadequately explored. To bridge the knowledge gap, this study focuses on enhancing Oleoylethanolamine (OEA), a precursor molecule that instigates satiety, promotes lipolysis and extends the life span of model system, Caenorhabditis elegans. TRIF regimen in C. elegans induces OEA, which in turn lead to satiety followed by lipolysis and ATP synthesis. Lipolysis is stimulated by the increase in Adipose Tissue Triglyceride Lipase-1 (ATGL-1) activity that results from the enrichment in OEA precursor. In addition, the TRIF regimen induces oxidative stress resistance in C. elegans. Subsequently, this promotes longevity and slow aging in C. elegans by altering the insulin/ insulin-like growth factor signaling (IIS) pathway. The present study suggested the beneficial effects of time-restricted fasting in the eukaryotic model nematodes through the activation of lipid metabolism that involves enhanced production of OEA precursors which promotes lipolysis. In addition, the data revealed that the increased ATP production resulted in oxidative stress tolerance that promoted longevity and slow aging processes.