Biology subjects

Morrison, C. D.

Publications and source records attributed to Morrison, C. D..

3 recordsLinked to original sources

bioRxiv2025

FGF21 signals through KLB-expressing glutamatergic neurons in the hindbrain to mediate the effects of dietary protein restriction

Animals adaptively respond to protein restriction by altering both behavior and metabolism. Previous work demonstrated that the metabolic hormone FGF21 acted in the brain to coordinate these adaptive responses, but the exact site of action remains unclear. Here, we identify a discrete population of glutamatergic, Klb-expressing neurons in the nucleus of the solitary tract (NTS), demonstrating that these neurons are key to mediating FGF21 action during protein restriction. Using a novel Klb-Flp mouse line combined with intersectional genetics, we demonstrate that these neurons are directly activated by FGF21. While previous work implicated the SCN, PVN, and VMH in FGF21 action, we find that these areas do not impact the response to protein restriction. Instead, selective ablation of NTS-KLB neurons prevents metabolic adaptations to protein restriction (food intake, food choice, and energy expenditure), while their chemogenetic activation is sufficient to drive these responses. These findings establish NTS-KLB neurons as a critical node for detecting protein status and coordinating whole-body metabolic responses, providing new insight into how the brain monitors and maintains protein homeostasis.

neuroscience↗

bioRxiv2024

Long-Term Effects of Early Adolescent Second-Generation Antipsychotic Exposure on Body Weight, Caloric Intake, and Metabolism-Associated Gene Expression

The use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. During high-fat diet feeding, some groups of treated mice gained weight at higher rates than their respective control groups, but the finding was not consistent across experiments. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.

pharmacology and toxicology↗

bioRxiv2024

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation as compared to casein in control-fed mice, whereas casein triggered a larger activation in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data strongly suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

neuroscience↗