Obesity Genes and Insulin Resistance

Overview

Journal Curr Opin Endocrinol Diabetes Obes

Specialty Endocrinology

Date 2010 Jun 30

PMID 20585247

Citations 35

Authors

Anna C Belkina

Gerald V Denis

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of 'metabolically healthy but obese' (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review.

Recent Findings: The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D.

Summary: Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients.

Citing Articles

Genetics-driven risk predictions leveraging the Mendelian randomization framework.

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Specific Genotypes Associated with Differences in Fasting Insulin Levels and Body Mass Index in Healthy Young Males: Implications for Gene-Nutrient Interactions-an Exploratory Study.

Brown J, Pham T, Burden H, Braakhuis A Curr Dev Nutr. 2023; 7(11):102018.

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A cardiac amino-terminal GRK2 peptide inhibits insulin resistance yet enhances maladaptive cardiovascular and brown adipose tissue remodeling in females during diet-induced obesity.

Manaserh I, Bledzka K, Ampong I, Junker A, Grondolsky J, Schumacher S J Mol Cell Cardiol. 2023; 183:81-97.

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Unraveling the Host Genetic Background Effect on Internal Organ Weight Influenced by Obesity and Diabetes Using Collaborative Cross Mice.

Ghnaim A, Lone I, Ben Nun N, Iraqi F Int J Mol Sci. 2023; 24(9).

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