Investigating the role of lipid metabolism in germline-soma interactions and stress responses

The National Institute of General Medical Sciences awarded the University of New Orleans $372,500 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859, Assistance Type: Project Grant) to investigate the role of lipid metabolism in germline-soma interactions and stress responses using Caenorhabditis elegans as a model organism.

The research examines how increased germline activity—specifically in mated hermaphrodite worms compared to self-fertilized worms—alters lipid metabolism in somatic tissue and influences somatic homeostasis and stress responsiveness. Prior work by the principal investigator found that mated worms experience reduced fat storage, increased susceptibility to osmotic, oxidative, and temperature stresses, and shorter lifespans. The project addresses three major research questions: how an active germline induces somatic loss of neutral lipids and phospholipids; the extent and mechanisms by which germline-induced lipid depletion influences somatic function; and what role lipid metabolism plays in coordinating germline-soma interactions under stress conditions.

The period of performance runs from September 1, 2026, through May 31, 2031, with work performed in New Orleans, Louisiana. The award supports basic research under NIGMS's mission to increase understanding of biological processes and lay the foundation for advances in disease diagnosis, treatment, and prevention.

Abstract

Coordinating the functions of germline and soma in varied physiological states and adapting to changing environments is crucial for the well-being of multicellular organisms. Studies using germline-removed model organisms have significantly increased our understanding of how somatic functions are regulated in response to the limitation of reproduction. However, the mechanism through which increased reproduction or elevated germline activity influences somatic functions remains elusive. The reproductive mode of caenorhabditis elegans provides a unique opportunity to investigate how an active germline impacts the soma. In hermaphrodite worms, germline activity is significantly increased after mating with males compared to self-fertilization. In our previous work, we found that mated worms experience a reduction in FAT storage, increased susceptibility to various stresses (such as osmotic, oxidative, and temperature stresses), and ultimately exhibit a shorter lifespan compared to unmated, self-fertilized worms. Despite observing a substantial loss of FAT storage in mated worms, IT remains unclear how lipid metabolism changes with increased reproduction and, specifically, what role lipid metabolism plays in coordinating the functions of germline and soma. We hypothesize that germline hyperactivity alters lipid metabolism in the soma, which in turn influences the somatic homeostasis and stress responsiveness of mated worms. Using mated worms as the model, we aim to understand the interconnections between reproduction, somatic health, and environmental responses. Three major research questions we are addressing in the lab include: (1) how does an active germline induce the somatic loss of major lipid classes, including neutral lipids and phospholipids? (2) to what extent, and through which mechanisms, does germline-induced lipid depletion influence somatic functions? (3) what role does lipid synthesis play in mediating somatic changes under high reproductive demand? We anticipate that these investigations will provide new insights into the mechanisms through which different tissues coordinate their functions in diverse physiological states and respond to fluctuating environments.