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.

Fig. 1

Muscle building and fat lowering effects of repartitioning agents and myostatin inhibition. A Cross-sections at the 10th rib of pigs [19]. Left represents a pig treated with 3 mg clenbuterol/kg feed for 4 weeks, plus a 3-week course of daily injections of 0.1 mg recombinant porcine growth hormone/kg liveweight. Right represents a typical control animal. B Belgian blue bull showing double muscling and low fat mass. These animals have “natural” mutations of the muscle mass-inhibiting Mstn gene. [Copyright (1997) National Academy of Sciences] [20]

Fig. 2

Scatter plots of the effect of muscle hypertrophy on fat mass changes. A represents changes in muscle mass/fat mass from pre- to post-intervention in humans. The green dashed line indicates the regression line of the pharmaceutical treatment (n = 15, k = 21), while the black dashed line includes all other treatments (n = 82, k = 109). The size of each data point represents the sample size. B represents relative differences in muscle mass versus relative differences in fat mass between experimental group and controls in animal models. The green dashed line indicates the regression line of the pharmaceutical treatment (n = 5, k = 9), while the black dashed line includes all other treatments (n = 16, k = 23)

Fig. 3

Scatter plots of the effect of muscle hypertrophy on glucose homeostasis. The dashed lines indicate the linear regression. A represents changes in muscle mass and fasted glucose or HbA1c concentrations from pre- to post-intervention in humans (n = 22, k = 31). The size of each data point represents the sample size. B represents relative differences in muscle mass versus differences in blood glucose concentration between experimental groups and controls in animal models (n = 10, k = 12)

Fig. 4

Mechanisms that explain the effects of muscle hypertrophy on fat mass and glucose homeostasis. A Akt1 and myostatin are examples of regulators whose action on muscle is enough to cause a loss of fat mass and improvement of glucose homeostasis. B In contrast, the catecholamines adrenaline and noradrenaline, as well β-adrenergic agonists, act both on skeletal muscle and adipose tissue as both tissues express adrenergic receptors. C Inter-organ signal transduction mechanisms (e.g., in response to resistance exercise) versus D metabolic mechanisms (e.g., β-adrenergic agonist effects on skeletal muscle and adipose tissue metabolism; [170]) that can potentially explain the effects of muscle hypertrophy on fat and glucose