Preclinical rodent models of physical inactivity-induced muscle insulin resistance: challenges and solutions

Physical inactivity influences the development of muscle insulin resistance yet is far less understood than diet-induced muscle insulin resistance. Progress in understanding the mechanisms of physical inactivity-induced insulin resistance is limited by a lack of an appropriate preclinical model of muscle insulin resistance. Here, we discuss differences between diet and physical inactivity-induced insulin resistance, the advantages and disadvantages of the available rodent inactivity models to study insulin resistance, and our current understanding of the mechanisms of muscle insulin resistance derived from such preclinical inactivity designs. The burgeoning rise of health complications emanating from metabolic disease presents an alarming issue with mounting costs for health care and a reduced quality of life. There exists a pressing need for more complete understanding of mechanisms behind the development and progression of metabolic dysfunction. Since lifestyle modifications such as poor diet and lack of physical activity are primary catalysts of metabolic dysfunction, rodent models have been formed to explore mechanisms behind these issues. Particularly, the use of a high-fat diet has been pervasive and has been an instrumental model to gain insight into mechanisms underlying diet-induced insulin resistance (IR). However, physical inactivity (and to some extent muscle disuse) is an often overlooked and much less frequently studied lifestyle modification, which some have contended is the primary contributor in the initial development of muscle IR. In this mini-review we highlight some of the key differences between diet- and physical inactivity-induced development of muscle IR and propose reasons for the sparse volume of academic research into physical inactivity-induced IR including infrequent use of clearly translatable rodent physical inactivity models.