Dusabyinema, Y. | Search bioRxiv

bioRxiv2024

Semaglutide interferes with postnatal growth in a diet-dependent manner

GLP-1 receptor agonists, including semaglutide, are increasingly used to treat obesity--and to a lesser extent, type 2 diabetes--in children and adolescents. Despite their therapeutic promise, the impact of semaglutide on key endocrine and metabolic developmental processes during this period is not yet fully understood. To address the limited understanding of GLP-1 receptor agonists during development, we investigated the effects of chronic semaglutide treatment on growth and metabolism of weanling male mice. In juvenile mice displaying a normal growth pattern, semaglutide lowered blood glucose without affecting food intake or weight gain. In contrast, chronic semaglutide treatment in growth-stunted juveniles exacerbated linear growth impairment, despite preserving glucose-lowering effects. Transcriptomic analysis of the liver, complemented by gene expression studies in other metabolically active tissues, suggested altered energy expenditure, indicating a complex interaction between semaglutide, energy metabolism, and growth during juvenile development. These findings underscore the importance of developmental context when evaluating the safety and efficacy of GLP-1 receptor agonists in pediatric populations.

physiology↗

bioRxiv2023

Larval microbiota primes the Drosophila adult gustatory response

The survival of animals depends, among other things, on their ability to identify threats in their surrounding environment. Senses such as olfaction, vision and taste play an essential role in sampling their living environment, including microorganisms, some of which are potentially pathogenic. This study focuses on the mechanisms of detection of bacteria by the Drosophila gustatory system. We demonstrate that the peptidoglycan (PGN) that forms the cell wall of bacteria triggers an immediate feeding aversive response when detected by the gustatory system of adult flies. Although we identify ppk23+ and Gr66a+ gustatory neurons as necessary to transduce fly response to PGN, we demonstrate that they play very different roles in the process. Time-controlled functional inactivation and in vivo calcium imaging demonstrate that while ppk23+ neurons are required in the adult flies to directly transduce PGN signal, Gr66a+ neurons must be functional in larvae to allow future adults to become PGN sensitive. Furthermore, the ability of adult flies to respond to bacterial PGN is lost when they hatch from larvae reared under axenic conditions. Recolonization of axenic larvae, but not adults, with a single bacterial species, Lactobacillus brevis, is sufficient to restore the ability of adults to respond to PGN. Our data demonstrate that the genetic and environmental characteristics of the larvae are essential to make the future adults competent to respond to certain sensory stimuli such as PGN.

animal behavior and cognition↗