GLP-1 physiology informs the pharmacotherapy of obesity

Molecular Metabolism, Journal Year: 2021, Volume and Issue: 57, P. 101351 - 101351

Published: Oct. 8, 2021

Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake body weight, fostering investigation GLP1RA obesity. Here I discuss physiology (GLP-1) action in control animals humans, highlighting importance gut vs. brain-derived GLP-1 feeding weight. The widespread distribution function multiple (GLP1R) populations central autonomic nervous system are outlined, pathways controlling energy expenditure preclinical studies reduction both humans is highlighted. relative contributions vagal afferent GLP1R+ physiological anorectic response to compared reviewed. Key data two obesity therapy (liraglutide 3 mg daily semaglutide 2.4 once weekly) discussed. Finally, emerging potentially supporting combination with additional peptide epitopes unimolecular multi-agonists, as well fixed-dose therapies, actions weight highly conserved obese adolescents adults. well-defined mechanisms through a single G protein-coupled receptor, together extensive safety database people T2D, provide reassurance surrounding long-term use these co-morbidities. may be effective conditions associated obesity, such cardiovascular disease non-alcoholic steatohepatitis (NASH). Progressive improvements efficacy suggest that GLP-1-based therapies soon rival bariatric surgery viable options its complications.

Language: Английский

---

Internal senses of the vagus nerve

Neuron, Journal Year: 2022, Volume and Issue: 110(4), P. 579 - 599

Published: Jan. 19, 2022

Language: Английский

---

Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(2), P. 314 - 328

Published: Sept. 7, 2021

Abstract The central nervous system (CNS) receives information from afferent neurons, circulating hormones, and absorbed nutrients integrates this to orchestrate the actions of neuroendocrine autonomic systems in maintaining systemic metabolic homeostasis. Particularly arcuate nucleus hypothalamus (ARC) is pivotal importance for primary sensing adiposity signals, such as leptin insulin, nutrients, glucose. Importantly, energy state–sensing neurons ARC not only regulate feeding but at same time control multiple physiological functions, glucose homeostasis, blood pressure, innate immune responses. These findings have defined them master regulators, which adapt integrative physiology state organism. disruption fine-tuned leads an imbalance between intake expenditure well deregulation peripheral metabolism. Improving our understanding cellular, molecular, functional basis regulatory principle CNS could set stage developing novel therapeutic strategies treatment obesity syndrome. In review, we summarize insights with a particular emphasis on neurocircuitries regulating food homeostasis factors that inform brain organismal status.

Language: Английский

---

The expanding incretin universe: from basic biology to clinical translation

Diabetologia, Journal Year: 2023, Volume and Issue: 66(10), P. 1765 - 1779

Published: March 28, 2023

Language: Английский

---

The microbiota–gut–brain axis and neurodevelopmental disorders

Protein & Cell, Journal Year: 2023, Volume and Issue: 14(10), P. 762 - 775

Published: May 11, 2023

Abstract The gut microbiota has been found to interact with the brain through microbiota–gut–brain axis, regulating various physiological processes. In recent years, impacts of on neurodevelopment this axis have increasingly appreciated. is commonly considered regulate three pathways, immune pathway, neuronal and endocrine/systemic overlaps crosstalks in between. Accumulating studies identified role neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity Rett Syndrome. Numerous researchers examined pathophysiological mechanisms influenced by (NDDs). This review aims provide a comprehensive overview advancements research pertaining microbiota-gut-brain NDDs. Furthermore, we analyzed both current state progress discuss future perspectives field.

Language: Английский

---

An inter-organ neural circuit for appetite suppression

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2478 - 2494.e28

Published: June 2, 2022

Language: Английский

---

The physiological control of eating: signals, neurons, and networks

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 689 - 813

Published: Sept. 6, 2021

During the past 30 yr, investigating physiology of eating behaviors has generated a truly vast literature. This is fueled in part by dramatic increase obesity and its comorbidities that coincided with an ever increasing sophistication genetically based manipulations. These techniques have produced results remarkable degree cell specificity, particularly at signaling level, played lead role advancing field. However, putting these findings into brain-wide context connects physiological signals neurons to behavior somatic requires thorough consideration neuronal connections: field also seen extraordinary technological revolution. Our goal present comprehensive balanced assessment how associated energy homeostasis interact many brain levels control behaviors. A major theme engage sets interacting neural networks throughout are defined specific connections. We begin discussing some fundamental concepts, including ones still engender vigorous debate, provide necessary frameworks for understanding controls meal initiation termination. include key word definitions, ATP availability as pivotal regulated variable homeostasis, neuropeptide signaling, homeostatic hedonic eating, structure. Within this context, we discuss network models regions endbrain (or telencephalon), hypothalamus, hindbrain, medulla, vagus nerve, spinal cord work together gastrointestinal tract enable complex motor events permit animals eat diverse situations.

Language: Английский

---

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Circulation Research, Journal Year: 2022, Volume and Issue: 130(8), P. 1112 - 1144

Published: April 14, 2022

The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their host. Many environmental host-related factors affect the microbiota. Dysbiosis defined as compositional functional alterations of microbiota that contribute to pathogenesis, progression treatment responses disease. occurs when perturbations composition function exceed ability its host restore symbiotic state. leads dysfunctional signaling MGBA, which regulates development host’s immune, metabolic, nervous systems. Dysbiosis-induced dysfunction MGBA seen with aging stroke, linked common stroke risk such obesity, diabetes, atherosclerosis. Changes in are also response may impair recovery after injury. This review will begin an overview tools used study discussion on limitations potential experimental confounders. Relevant components introduced summarized for better understanding age-related changes stroke. We then focus relationship aging, highlighting all undergo can be influenced by or even driven In final section, current clinical preclinical evidence role hypertension, frailty summarized, well populations. conclude describing microbiota-based therapies including use pre-/pro-biotics supplementations bacterial metabolites. Ongoing progress this new frontier biomedical sciences lead improved MGBA’s impact human health

Language: Английский

---

Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Language: Английский

---

Integrative neurocircuits that control metabolism and food intake

Science, Journal Year: 2023, Volume and Issue: 381(6665)

Published: Sept. 28, 2023

Systemic metabolism has to be constantly adjusted the variance of food intake and even prepared for anticipated changes in nutrient availability. Therefore, brain integrates multiple homeostatic signals with numerous cues that predict future deviations energy supply. Recently, our understanding neural pathways underlying these regulatory principles-as well as their convergence hypothalamus key coordinator intake, expenditure, glucose metabolism-have been revealed. These advances have changed view brain-dependent control metabolic physiology. In this Review, we discuss new concepts about how alterations contribute development prevalent diseases such obesity type 2 diabetes mellitus emerging knowledge may provide targets treatment.

Language: Английский

---