Abstract
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 sequelae. 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.
Highlights
Obesity (body mass index (BMI) ≥ 30.0 kg/m2 ) [1] is an escalating global health challenge affecting 13% of the world’s population, according to recent World HealthOrganization estimates [2]
High-fat-diet-induced obesity in male C57BL/6 mice was associated with impaired vasoconstriction in second-order arterioles compared to male control, whereas diet-induced obesity in the female model resulted in significant alterations in both arteriolar vasodilation and vasoconstrictor responses compared to a female control [83]
The chronic inflammatory phenotype seen in obesity and diabetes mellitus (DM) type 2 induces compositional changes in the extracellular matrix (ECM), including increased expression of ECM proteins such as collagen, and glycosaminoglycans such as hyaluronan, which are a major constituent of the capillary luminal endothelial cell glycocalyx [138,139]
Summary
Obesity (body mass index (BMI) ≥ 30.0 kg/m2 ) [1] is an escalating global health challenge affecting 13% of the world’s population, according to recent World Health. Skeletal muscle microvascular and metabolic physiology and pathophysiology are closely linked, and a growing body of evidence has confirmed the critical role of microvascular dysfunction (inadequate microvascular response to physiologic metabolic demand or challenge) in the mediation of obesity-related insulin resistance [12–15]. The aim of this paper was to review the general background of the relationship between skeletal muscle microvascular and metabolic physiology, as a point of departure to explore the etiological role of microvascular dysfunction in obesity-related insulin resistance. It highlights the therapeutic implications of the elucidated pathophysiological mechanisms and correlates the currently available or potential pharmacological agents that bear important therapeutic relevance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
