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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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The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...
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Related Experiment Video

Updated: Jun 4, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
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Melanocortin 4 receptor mutation in obesity.

Gumpeny R Sridhar1, Lakshmi Gumpeny2

  • 1Department of Endocrinology and Diabetes, Endocrine and Diabetes Centre, Visakhapatnam 530002, Andhra Pradesh, India. sridharvizag@gmail.com.

World Journal of Experimental Medicine
|December 23, 2024
PubMed
Summary

Genetic mutations in the melanocortin 4 receptor (MC4R) pathway cause obesity. Targeted therapies like Setmelanotide offer new hope for managing this condition effectively.

Keywords:
Cyclic AMPDownstreamG proteinLeptin-melanocortin pathwayMutationObesity syndromesScreeningSetmelanotide

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Area of Science:

  • Endocrinology
  • Genetics
  • Metabolic Diseases

Background:

  • Obesity is a global health concern with significant genetic underpinnings.
  • The hypothalamic leptin-melanocortin pathway, involving melanocortin 4 receptors (MC4R), is crucial for appetite and weight regulation.
  • Mutations in MC4R are a known cause of both syndromic and non-syndromic obesity.

Purpose of the Study:

  • To review the role of MC4R mutations in obesity.
  • To discuss the classification and clinical manifestations of MC4R mutations.
  • To highlight current and future therapeutic strategies for MC4R-associated obesity.

Main Methods:

  • Literature review of genetic factors in obesity.
  • Analysis of the hypothalamic leptin-melanocortin pathway and MC4R function.
  • Examination of clinical data and therapeutic outcomes for MC4R mutations.

Main Results:

  • MC4R mutations disrupt appetite control, leading to early-onset obesity, hyperphagia, and metabolic issues.
  • Mutations are categorized by their effect on receptor function (e.g., null, retention, binding, signaling).
  • Setmelanotide, an MC4R agonist, demonstrates efficacy in weight reduction and symptom management without cardiovascular side effects.

Conclusions:

  • MC4R mutations are a significant genetic cause of obesity, presenting with specific clinical features.
  • Targeted therapies like Setmelanotide represent a breakthrough in managing MC4R-related obesity.
  • Further research into MC4R epidemiology, signaling, and novel therapeutics is essential for advancing obesity prevention and treatment.