Skeletal muscle microvascular dysfunction in obesity-related insulin resistance : pathophysiological mechanisms and therapeutic perspectives

Ugwoke, Chiedozie Kenneth (author), Cvetko, Erika (author), Umek, Nejc (author)

Obesity is a worrisomely escalating public health problem globally and one of the leading causes of morbidity and mortality from noncommunicable disease. The epidemiological link between obesity and a broad spectrum of cardiometabolic disorders has been well documented; however, the underlying pathophysiological mechanisms are only partially understood, and effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle has increasingly become a focus of attention in understanding the mechanisms of impaired insulin function in obesity and the associated metabolic sequalae. We examined the current evidence on the relationship between microvascular dysfunction and insulin resistance in obesity. A growing body of evidence suggest an intimate and reciprocal relationship between skeletal muscle microvascular and glucometabolic physiology. The obesity phenotype is characterized by structural and functional changes in the skeletal muscle microcirculation which contribute to insulin dysfunction and disturbed glucose homeostasis. Several interconnected etiologic molecular mechanisms have been suggested, including endothelial dysfunction by several factors, extracellular matrix remodelling, and induction of oxidative stress and the immunoinflammatory phenotype. We further correlated currently available pharmacological agents that have deductive therapeutic relevance to the explored pathophysiological mechanisms, highlighting a potential clinical perspective in obesity treatment.

• Language: English
• Keywords: microvascular dysfunction, insulin resistance, obesity treatment, obesity, skeletal muscle
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 22 str.
• Numbering: Vol. 23, iss. 2, art. 847
• PID: 20.500.12556/RUL-137128
• UDC: 611
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms23020847
• COBISS.SI-ID: 93446147
• Publication date in RUL: 01.06.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 13.01.2022

Secondary language

• Language: Slovenian
• Keywords: mikrovaskularna disfunkcija, odpornost proti insulinu, zdravljenje debelosti

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0043
• Name: Molekularni mehanizmi razvoja in delovanja skeletne mišice