Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations

Abstract

Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

Figure 1

Exercise training increases the beiging of scWAT. A–C: Mice were housed in wheel cages for 11 days of exercise training, and scWAT was analyzed. Prdm16 (A) and Ucp1 (B) mRNA of trained scWAT was increased compared with sedentary scWAT, and Prdm16 expression was increased to the expression level of BAT (n = 7/group). *P < 0.05, ***P < 0.001. (C) Hematoxylin-eosin staining revealed the presence of multilocular droplets in the trained subcutaneous adipose tissue (solid arrowheads indicate the presence of multilocular droplets; open arrowheads indicate blood vessels). Adapted with permission from Chechi et al. (31). A.U., arbitrary unit.

Figure 2

Exercise training increases mitochondrial biogenesis in WAT. A: OCR was significantly increased in trained scWAT (11 days of wheel cage running) compared with scWAT from sedentary mice (n = 7/group). **P < 0.01. Adapted with permission from Chechi et al. (31). B: Genes involved in mitochondrial biogenesis after 30 days of exercise training in scWAT in wild-type (WT) and eNOS^−/− mice (n = 8) *P < 0.05, **P < 0.01 relative to sedentary controls; †P < 0.05, ††P < 0.01 relative to WT mice. Adapted with permission from Craig et al. (15).

Figure 3

Transplantation of trained scWAT improves glucose tolerance and increases whole-body insulin sensitivity. A and B: Mice were transplanted with 0.85 g scWAT from trained or sedentary mice or were sham operated. For glucose tolerance tests (GTTs), mice were injected with glucose 2 g/kg body weight i.p. A: GTT at 9 days posttransplantation. B: Glucose area above baseline (AAB) at 9, 14, and 28 days posttransplantation. Data are mean ± SEM (n = 5–12/group). **P < 0.01, ***P < 0.001. Adapted with permission from Chechi et al. (31).

Figure 4

Exercise training–induced adipokines have an endocrine effect and improve whole-body metabolism. We propose a model whereby exercise causes WAT to release adipokines, which can act in an endocrine manner to improve metabolism in skeletal muscle, liver, and BAT or in an autocrine or paracrine manner to improve WAT function.