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Related Concept Videos

Hormonal Regulation01:40

Hormonal Regulation

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Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
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Intestinal Phase of Digestion01:29

Intestinal Phase of Digestion

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The intestinal phase of digestion is the third and final stage of the digestive process, occurring after the cephalic and gastric phases. It begins when chyme, a partially digested mixture of food and digestive enzymes, enters the small intestine from the stomach. This phase is crucial for nutrient absorption and involves complex hormonal and enzymatic interactions.
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Regulation of Food Intake01:30

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Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Hormones Secreted by the Stomach01:25

Hormones Secreted by the Stomach

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Enteroendocrine cells, accounting for only 1% of stomach epithelial cells, play a significant role in digestion and are classified by their digestive hormone secretions.
Each of these hormones secreted by different enteroendocrine cells plays a unique role in digestion. Here are a few examples:
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Gastric Phase of Digestion01:26

Gastric Phase of Digestion

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The gastric phase of digestion begins as soon as food enters the stomach. The incoming food bolus triggers neural and hormonal mechanisms, which last approximately 3 to 4 hours. During this phase, the stomach undergoes significant changes to prepare the food for further digestion and absorption.
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Related Experiment Video

Updated: Jun 3, 2025

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Ghrelin-LEAP2 interactions along the stomach-liver axis.

Katsuya Sakai1, Yuki Nakazato1, Yuki Shiimura2,3

  • 1Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.

Endocrine Journal
|January 5, 2025
PubMed
Summary

Ghrelin and liver-expressed antimicrobial peptide (LEAP2) interact with the same receptor (GHSR) to regulate body weight and food intake. LEAP2 antagonizes ghrelin, with elevated LEAP2 and reduced ghrelin observed in obesity.

Keywords:
G protein-coupled receptor (GPCR)GhrelinGrowth hormone secretagogue receptor (GHSR)Liver-expressed antimicrobial peptide 2 (LEAP2)Peptide

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Area of Science:

  • Endocrinology
  • Metabolism
  • Molecular Biology

Background:

  • Ghrelin, a stomach-produced peptide, stimulates food intake and growth hormone (GH) secretion, acting as an anabolic agent during starvation.
  • Ghrelin exerts its effects by binding to the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor (GPCR).
  • Anamorelin, a ghrelin agonist, is approved for cancer cachexia, highlighting ghrelin's therapeutic potential.

Purpose of the Study:

  • To investigate the role of liver-expressed antimicrobial peptide (LEAP2) in regulating appetite and metabolism.
  • To understand the interaction between ghrelin and LEAP2 at the GHSR.
  • To explore the implications of these interactions in obesity and metabolic regulation.

Main Methods:

  • Literature review and analysis of existing studies on ghrelin, LEAP2, and GHSR.
  • Examination of data on LEAP2 upregulation in diet-induced obesity models.
  • Analysis of correlations between serum LEAP2 concentrations and metabolic parameters like BMI, body fat, glucose, and triglycerides.

Main Results:

  • LEAP2, initially identified as an antimicrobial peptide, antagonizes ghrelin's activity at the GHSR.
  • LEAP2 expression is upregulated in the stomach following vertical sleeve gastrectomy in obese mice.
  • Serum LEAP2 concentrations are positively correlated with obesity indicators (BMI, body fat) and metabolic dysfunction (glucose, triglycerides), while ghrelin levels are reduced in obesity.

Conclusions:

  • Ghrelin and LEAP2 are key regulators of body weight, food intake, and glucose homeostasis through their opposing actions on the GHSR.
  • LEAP2 emerges as a potential therapeutic target for obesity and related metabolic disorders.
  • The balance between ghrelin and LEAP2 signaling at the GHSR is crucial for maintaining metabolic health.