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Genome wide transcriptional changes underlie gradual and recurrent adaptation to protein malnutrition in zebrafish

ABSTRACT: Lysosome-rich enterocytes (LREs) are a specialized population of intestinal cells that mediate the uptake and absorption of dietary proteins in zebrafish and neonatal mammals. Loss of LRE function causes severe stunting and poor survival due to protein malnutrition. Previously, we reported that loss of Plasmolipin (pllp), an endosomal membrane protein highly expressed in LREs, impairs LRE differentiation and dietary protein absorption, resulting in marked reduction in survival rates. Raising pllp homozygous mutants surviving to adulthood and in-crossing them for multiple generations resulted in their adaptation to malnutrition, with pllp mutants showing robust suppression of survival deficits. To uncover mechanisms underlying this adaptive response, we conducted transcriptome profiling and protein absorption assays to compare the older adapted pllp allele with genetically related wild type (WT) fish and a newly generated pllp mutant allele. We found that adapted pllp mutants exhibit upregulation of LRE endocytic components and have a capacity for protein absorption that exceeds that of WT. This hyperactivation of LRE endocytic and absorptive activity, appears also to be aided by the intricate transcriptional regulations of immune genes that may contribute to the enhanced survival of pllp mutants in the face of increased exposure to environmental antigens. Overall, our study illustrates a genetic adaptation mechanism for enhancing organ function and organismal survival in response to severe protein malnutrition.

ORGANISM(S): Danio rerio

PROVIDER: GSE320085 | GEO | 2026/07/30

REPOSITORIES: GEO

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