Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search

Abstract

Overweight, obesity, and type 2 diabetes mellitus are metabolic health problems and diseases that affect billions of people worldwide. Studies in animals and humans suggest that stimulating global muscle hypertrophy could be a treatment for these diseases, as some key studies suggest that stimulation of global muscle hypertrophy commonly reduces fat mass and improves glucose homeostasis. To analyse the effect of muscle hypertrophy on fat and glucose homeostasis in more detail, we systematically searched the literature and quantitatively analyzed 122 studies (humans: n = 99; animals: n = 23). This analysis reveals that a 1.9–3.3% increase in global muscle mass in humans is associated with 4.1 ± 5.8% lower fat mass, a mean relative reduction in HbA1c of 4.1 ± 4.6% from baseline, and a reduction of fasting glucose concentrations by 5.8 ± 7.3% in studies lasting 2 weeks to 3 years. In the animal studies analyzed, the researchers increased muscle mass by transgenesis, drugs, or resistance training by 17.7 ± 18.4%. This increase of muscle mass was associated with 23.7 ± 22.3% less fat mass. In the second part of this review, we discuss mechanisms by which muscle hypertrophy can affect fat mass and glucose homeostasis. We also discuss the potential use of hypertrophy-focused resistance training and muscle hypertrophy-stimulating drugs as treatments for people with overweight, obesity, and type 2 diabetes.