Work

Balanced dietary ARA:DHA enhances social behavior via polyunsaturated lysoglycerophospholipids-GPCR signaling

Year: 2025

Type: article

Abstract: • Balanced dietary ARA:DHA (1:1) ratio significantly enhances social behavior in honeybees. • The 1:1 ARA:DHA ratio specifically increases gut polyunsaturated lysoglycerophospholipids. • Polyunsaturated lysoglycerophospholipids act as key gut–brain signaling mediators modulating social behavior. • A balanced ARA:DHA diet upregulates brain genes involved in GPCR signaling and tryptophan metabolism. • These findings identify the polyunsaturated lysoglycerophospholipids–GPCR axis as a molecular mechanism linking dietary PUFA balance to social behavior. Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are key long-chain polyunsaturated fatty acids (LC-PUFAs) critical for infant neurodevelopment. Although their roles in cognitive and visual functions are well established, the effects of specific ARA:DHA ratios on social behavior remain unclear. Using the honeybee as a model, we systematically compared diets with varying ARA:DHA ratios and found that only a 1:1 ratio induced a unique gut lipid profile, markedly enhancing LC-PUFAs and amino acid metabolism. By applying a network-based integrative analysis of untargeted metabolomic and social behavioral data, we identified distinct lipid modules in the 1:1 group, with key polyunsaturated-lysophosphatidylcholines and -lysophosphatidylethanolamines emerging as central network hubs strongly associated with enhanced social interaction and improved cognitive performance. These polyunsaturated-lysophospholipids may serve as critical molecular mediators for PUFA-dependent gut–brain communication. In the brain, the 1:1 diet further triggered the upregulation of genes involved in tryptophan metabolism, fatty acid degradation, and G protein-coupled receptor signaling. Notably, this dietary condition increased the expression of MRJP2 and the crustacean cardioactive peptide receptor, both of which are implicated in social regulation. These findings suggest that a balanced ARA:DHA ratio promotes social behavior by shaping gut lipid composition—especially increasing polyunsaturated-lysophospholipids abundance—and modulating neural gene expression through PUFA-mediated signaling.

Source: Journal of Future Foods

DOI: 10.1016/j.jfutfo.2025.08.022