Novel neural pathways targeted by GLP-1R agonists and bariatric surgery DOI Creative Commons
Mohammed K. Hankir, Thomas A. Lutz

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Abstract The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide has revolutionized the treatment of obesity, with other gut hormone-based drugs lined up that show even greater weight-lowering ability in obese patients. Nevertheless, bariatric surgery remains mainstay for severe obesity and achieves unparalleled weight loss generally stands test time. While their underlying mechanisms action remain incompletely understood, it is clear common denominator between GLP-1R agonists they suppress food intake by targeting brain. In this Review, we highlight recent preclinical studies using contemporary neuroscientific techniques provide novel concepts neural control body reference to endogenous GLP-1, agonists, surgery. We start periphery vagal, intestinofugal, spinal sensory nerves then progress through brainstem hypothalamus finish at non-canonical brain feeding centers such as zona incerta lateral septum. Further defining commonalities differences terms how target may not only help bridge gap pharmacological surgical interventions but also a basis combined use when each individually fails.

Language: Английский

Sex-specific signatures of GLP-1 and amylin on resting state brain activity and functional connectivity in awake rats. DOI Creative Commons
Tanzil Mahmud Arefin, Stina Börchers,

Doris I. Olekanma

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110348 - 110348

Published: Feb. 1, 2025

Gut-produced glucagon-like peptide-1 (GLP-1) and pancreas-made amylin robustly reduce food intake by directly or indirectly affecting brain activity. While for both peptides a direct action in the hindbrain hypothalamus is likely, few studies examined their impact on whole activity rodents did so evaluating male under anesthesia. However, sex anesthesia may significantly alter influence of feeding controlling molecules Therefore, we investigated effect GLP-1 functional connectivity (FC) awake adult female rats using resting-state magnetic resonance imaging (rsfMRI). We further relationship between altered subsequent response to GLP-1. observed divergent effects FC patterns. Most importantly correlation analysis behavior revealed that different areas potentially drive reduced rats. Our findings underscore distributed distinctly neural network engaged each these anorexic suggest be primary drivers outcome Moreover, prominent alterations not typically associated with sexes either indicate novel centers alternatively involvement substances behaviors beyond metabolism. The latter question potential translational significance as analogues are clinically utilized.

Language: Английский

Citations

1
Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety DOI

Addison N. Webster,

Jordan J. Becker,

Chia Li

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Language: Английский

Citations

7
Hunger Games: A Modern Battle Between Stress and Appetite DOI Open Access

W. G. Smith,

Estefania P. Azevedo

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 1, 2025

ABSTRACT Stress, an evolutionarily adaptive mechanism, has become a pervasive challenge in modern life, significantly impacting feeding‐relevant circuits that play role the development and pathogenesis of eating disorders (EDs). Stress activates hypothalamic–pituitary–adrenal (HPA) axis, disrupts specific neural circuits, dysregulates key brain regions, including hypothalamus, hippocampus, lateral septum. These particular structures are interconnected integrating stress feeding signals, modulating hunger, satiety, cognition, emotional coping behaviors. Here we discuss interplay between genetic predispositions environmental factors may exacerbate ED vulnerability. We also highlight most commonly used animal models to study mechanisms driving EDs recent rodent studies emphasize discovery novel cellular molecular signals within hippocampus–lateral septum–hypothalamus axis. In this review, gut microbiome, emerging area research field unanswered questions persist hinder scientific progress, such as why some individuals remain resilient while others at high risk for EDs. finally need future delineating impact stressors on clarifying relevance functionality hippocampal–septal–hypothalamic connectivity, investigating neuropeptides CRH, oxytocin, GLP‐1 human pathogenesis. Emerging tools like single‐cell sequencing advanced imaging could uncover circuit‐level changes areas relevant patients. Ultimately, by basic clinical research, science offers promising avenues developing personalized, mechanism‐based treatments targeting maladaptive behavior patients suffering from image

Language: Английский

Citations

0
Lateral hypothalamus and eating: cell types, molecular identity, anatomy, temporal dynamics and functional roles DOI Creative Commons
Deok-Hyeon Cheon,

Shee‐June Park,

Jihyun Park

et al.

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

The lateral hypothalamus (LH) is a central hub orchestrating eating behavior through its complex cellular, anatomical and temporal organization. LH characterized by high heterogeneity functional complexity, with many aspects still unexplored. Here we synthesize recent advances in understanding the role of regulation across multiple dimensions. At cellular level, contains diverse neuronal populations that contribute to distinct roles behavior. Anatomically, divided into four regions-anteromedial, anterolateral, posteromedial posterolateral-each unique compositions, circuit organizations projection patterns. By integrating dynamics each cell type during behavior, identified how various types are involved regulating appetitive consummatory phases also plays vital associative learning different including homeostatic, pleasure-induced stress-induced eating. These insights organization function provide promising directions for therapeutic interventions disorders obesity, drugs, deep brain stimulation gene therapy.

Language: Английский

Citations

0
The neurobiology of overeating DOI Creative Commons
Garret D. Stuber, Valérie Schwitzgebel, Christian Lüscher

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Food intake serves to maintain energy homeostasis; however, overeating can result in obesity, which is associated with serious health complications. In this review, we explore the intricate relationship between overeating, and underlying neurobiological mechanisms. We review homeostatic hedonic feeding systems, highlighting role of hypothalamus reward systems controlling food balance. Dysregulation both these leads as seen genetic syndromes environmental models affecting appetite regulation when consuming highly palatable food. The concept "food addiction" examined, drawing parallels drug addiction. discuss cellular substrate for addiction-related behavior current pharmacological obesity treatments-in particular, GLP-1 receptor agonists-showcasing synaptic plasticity context exposure. A comprehensive model integrating insights from addiction research proposed guide effective interventions maladaptive behaviors. Ultimately, unraveling basis holds promise addressing pressing public issue obesity.

Language: Английский

Citations

0
An inhibitory GLP-1 circuit in the lateral septum modulates reward processing and alcohol intake in rodents DOI
Christian E. Edvardsson,

Davide Cadeddu,

Mia Ericson

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 115, P. 105684 - 105684

Published: April 17, 2025

Language: Английский

Citations

0
What Is the Role of Glucagon-Like Peptide 1 Signaling in the Nervous System and Its Potential Neuroprotective Effects? DOI
Pierpaolo Turcano, Rodolfo Savica, Eduardo E. Benarroch

et al.

Neurology, Journal Year: 2024, Volume and Issue: 103(4)

Published: July 30, 2024

Language: Английский

Citations

1
A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding DOI Creative Commons
Travis D. Goode, Jason Bondoc Alipio, B Antoine

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

SUMMARY Adaptive regulation of feeding depends on linkage internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation underlying cell-types circuitry is lacking. Here, we identify an evolutionary conserved discrete Prodynorphin ( Pdyn )-expressing subpopulation Somatostatin Sst inhibitory neurons the dorsolateral septum (DLS) that receives primarily dorsal, not ventral, hippocampal inputs. DLS( ) inhibit LHA GABAergic confer context- state-dependent calibration feeding. Viral deletion DLS mimicked effects seen optogenetic silencing INs, suggesting potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling food-seeking. Together, our findings illustrate how dorsal hippocampus evolved to recruit ancient circuit module through link information consumption. HIGHLIGHTS receive dense input from ventral Silencing hippocampus-DLS( )-LHA nodes abolishes context-conditioned necessary

Language: Английский

Citations

1
Novel neural pathways targeted by GLP-1R agonists and bariatric surgery DOI Creative Commons
Mohammed K. Hankir, Thomas A. Lutz

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Abstract The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide has revolutionized the treatment of obesity, with other gut hormone-based drugs lined up that show even greater weight-lowering ability in obese patients. Nevertheless, bariatric surgery remains mainstay for severe obesity and achieves unparalleled weight loss generally stands test time. While their underlying mechanisms action remain incompletely understood, it is clear common denominator between GLP-1R agonists they suppress food intake by targeting brain. In this Review, we highlight recent preclinical studies using contemporary neuroscientific techniques provide novel concepts neural control body reference to endogenous GLP-1, agonists, surgery. We start periphery vagal, intestinofugal, spinal sensory nerves then progress through brainstem hypothalamus finish at non-canonical brain feeding centers such as zona incerta lateral septum. Further defining commonalities differences terms how target may not only help bridge gap pharmacological surgical interventions but also a basis combined use when each individually fails.

Language: Английский

Citations

1