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Targeting Ghrelin for Developing Anti-Obesity Therapeutics

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Overview

Ghrelin has been a key focus in obesity research due to its role in appetite stimulation and energy balance regulation. Previous studies have explored various pharmacological interventions, including neutralizing circulating ghrelin, developing receptor antagonists, and investigating the role of ghrelin-O-acyltransferase (GOAT) inhibitors. Early experiments in animal models demonstrated potential, but translating these findings to effective anti-obesity therapies in humans has faced significant challenges, such as inconsistent long-term effects, counter-regulatory mechanisms, and safety concerns.

Fig.1 Physiological actions of ghrelin.Fig.1 Physiological actions of ghrelin: schematic illustrating the various hormonal actions of ghrelin in different target organs. ACTH, adrenocorticotropic hormone. GH, growth hormone. IGF-1, insulin-like growth factor 1. Up/down arrows denote increase/decrease. (Colldén, et al., 2017)

Target Ghrelin for Lasting Weight Control

Targeting ghrelin for developing anti-obesity therapeutics at Protheragen focuses on the Hormone's Pivotal Role in regulating hunger and energy balance. Its ability to influence weight gain makes it a compelling target for anti-obesity therapies. Protheragen is exploring multiple approaches to modulate ghrelin's effects.

Applications

  • Ghrelin is the only known hormone that actively stimulates hunger. By targeting GHSR, therapeutics can effectively reduce appetite, leading to decreased food intake, which is crucial for weight management.
  • Ghrelin influences energy balance by reducing energy expenditure. Inhibiting ghrelin or its pathways may boost energy expenditure, enhancing weight loss alongside reduced calorie intake.
  • Ghrelin plays a role in regulating glucose metabolism and fat storage. Targeting ghrelin may improve insulin sensitivity and glucose control, making it an attractive option for treating not only obesity but also metabolic disorders like type 2 diabetes.

Advantages

  • Since ghrelin is the primary hormone responsible for stimulating hunger, targeting it allows for more direct and potentially effective control over food intake, leading to significant reductions in calorie consumption.
  • Unlike other appetite-regulating hormones like leptin or glucagon-like peptide 1 (GLP-1) that signal fullness, ghrelin works by promoting hunger. Targeting ghrelin offers a novel mechanism for controlling weight by addressing the root cause of increased food intake.
  • The variability in ghrelin levels among individuals, particularly between obese and lean individuals, opens the possibility for personalized treatments.
Our Services

Targeting ghrelin in anti-obesity therapeutics involves understanding its role in hunger regulation and metabolism. Protheragen provides key services to explore ghrelin's impact on energy balance and fat storage. Here are some services that are highly relevant to the topic. You can also click "our service" to fully understand our services.

Adipocytokines Analysis Service

Ghrelin is part of the family of adipocytokines that regulate appetite, making this service useful for understanding its role in obesity.

Human Saliva Endocannabinoid Analysis Service

Since ghrelin is involved in hunger regulation, saliva analysis offers insights into its role in appetite control.

Adipose Tissue Cell Function Analysis Service

Studying how ghrelin affects adipose tissue and energy storage is crucial for therapeutic development.

Plasma Free Fatty Acid Metabolism Analysis Service

Ghrelin influences fat storage and metabolism, making this service important for understanding its metabolic effects.

Frequently Asked Questions

Are there any side effects associated with ghrelin-targeted therapies?

While targeting ghrelin holds promise, challenges such as compensatory mechanisms and balancing ghrelin's role in metabolism must be considered. Ongoing research at Protheragen is working to minimize any potential side effects.

What makes ghrelin a unique target for obesity treatment?

Ghrelin is the only hormone that directly stimulates hunger, making it a distinct and powerful target for reducing excessive food intake, which is a major driver of obesity.

Publication

Technology: Flow cytometry, Dual-luciferase reporter assay, MTT assay, Microarray gene expression profiling, Molecular docking with AutoDock, Surface plasmon resonance (SPR)

Journal: Pharmacology Research & Perspectives

Published: 2024

Results: The research highlights the dual role of ghrelin, particularly its ability to stimulate appetite and promote fat storage, which plays a significant role in energy balance and obesity. Ghrelin, also known as the "hunger hormone," primarily acts by binding to the GHSR in the hypothalamus, stimulating the neurons responsible for increasing food intake. It also influences brain regions related to reward, making calorie-dense foods more desirable, further linking ghrelin to the persistence of obesity. In addition, the study notes that ghrelin secretion increases during fasting and decreases postprandially, indicating its close regulation by energy states. Reduced levels of acyl ghrelin are found in obese individuals, although des-acyl ghrelin, which has opposite physiological actions, is more abundant.

Therapeutically, targeting the ghrelin pathway through GHSR antagonists, neutralization of circulating ghrelin, and inhibitors of GOAT are proposed strategies. Some drugs are in development but have not yet been fully effective in obesity treatments.

Fig.2 The network of hormonal regulation of the hypothalamic melanocortin system.Fig.2 Hormonal regulation of the hypothalamic melanocortin system. (Rubinić, et al., 2024)

Targeting ghrelin for developing anti-obesity therapeutics at Protheragen offers a unique and promising approach to controlling appetite and promoting sustainable weight loss. Please do not hesitate to contact us for more information and to explore solutions.

References

  1. Colldén, G.; et al. Therapeutic potential of targeting the ghrelin pathway. International Journal of Molecular Sciences. 2017, 18(4): 798.
  2. Rubinić, I.; et al. Novel pharmaceuticals in appetite regulation: Exploring emerging gut peptides and their pharmacological prospects. Pharmacology Research & Perspectives. 2024, 12(4): e1243.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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