Management of Oxidative Stress: Crosstalk Between Brown/Beige Adipose Tissues and Skeletal Muscles

Abstract

Exercise plays an important role in the physiology, often depending on its intensity, duration, and frequency. It increases the production of reactive oxygen species (ROS). Meanwhile, it also increases antioxidant enzymes involved in the oxidative damage defense. Prolonged, acute, or strenuous exercise often leads to an increased radical production and a subsequent oxidative stress in the skeletal muscles, while chronic regular or moderate exercise results in a decrease in oxidative stress. Notably, under pathological state, such as obesity, aging, etc., ROS levels could be elevated in humans, which could be attenuated by proper exercise. Significantly, exercise stimulates the development of beige adipose tissue and potentially influence the function of brown adipose tissue (BAT), which is known to be conducive to a metabolic balance through non-shivering thermogenesis (NST) and may protect from oxidative stress. Exercise-related balance of the ROS levels is associated with a healthy metabolism in humans. In this review, we summarize the integrated effects of exercise on oxidative metabolism, and especially focus on the role of brown and beige adipose tissues in this process, providing more evidence and knowledge for a better management of exercise-induced oxidative stress.

Keywords: beige adipose tissue; brown adipose tissue; crosstalk; exercise; oxidative stress; skeletal muscle.

Figure 1

Adaption of adipose tissues to exercises. Exercises increase fat mobilization, meanwhile exercised WAT releases various adipokines benefiting skeletal muscle function in many aspects. They could induce fatty acid oxidation, mitochondrial biogenesis, glucose uptake, muscle regeneration, and display anti-oxidative effect in skeletal muscle. Contracting muscles release various myokines, which may mediate exercise-induced beige adipose tissue development and probably promotes BAT function. Batokines released from brown/beige adipose tissues may influence skeletal muscle function by promoting the formation of mitochondrial cristae, fatty acid uptake and oxidation, and mitochondrial function. BAT, brown adipose tissue and WAT, white adipose tissue.

Figure 2

Mechanisms of ROS control in brown/beige adipocytes and the release of certain batokines, which target skeletal muscle. Physiological ROS enhances cAMP-p38 mitogen-activated protein kinase (MAPK) signaling to induce UCP1 expression in brown adipose tissue (BAT). UCP1, in turn, controls ROS production. Sestrin2, which is a stress-inducible protein, works as an antioxidant factor in BAT. However, over suppression of ROS by Sestrin2 results in an impaired upregulation of UCP1 after cold stimulation. Furthermore, ferroportin gene SLC40A1|FPN1, which mediates iron egress from cells, is downregulated in beige adipocytes, resulting in an iron accumulation. It is accompanied by an increased expression of carbonic anhydrases, CA3 and CA9, which mediate the protective effects on oxidative stress. BAT controls skeletal muscle function via the secretion of myostatin, which could be possibly prevented by IRF4. Additionally, 12,13-diHOME and FGF21, which are released from BAT, could also target skeletal muscles. CA, carbonic anhydrase; cAMP, cyclic adenosine monophosphate; 12,13-diHOME, 12,13-dihydroxy-9Z-octadecenoic acid; FGF21, fibroblast growth factor 21; IRF4, interferon regulatory factor 4; p38 MAPK, p38 mitogen-activated protein kinase; ROS, reactive oxygen species; and UCP1, uncoupling protein 1.

Figure 3

Crosstalk between skeletal muscle and brown/beige adipose tissues: importance of the balance of ROS levels. Contracting skeletal muscles produce a large amount of ROS. A cross talk between skeletal muscle and brown/beige adipose tissue, that certain batokines secreted from brown/beige adipose tissue control muscle function and various myokines secreted from contracting muscles promotes brown/beige adipose tissue function, may contribute to exercise-related ROS balance. ROS, reactive oxygen species.