A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice

Abstract

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.

Keywords: capsinoids; energy expenditure; exercise; fat oxidation; obesity.

Fig. 1.

Capsinoid (CSN) supplementation with exercise additively suppressed body weight gain and adiposity in diet-induced obesity. A: body weight development. B: body weight gain. C: tissue weight of C57BL/6J mice fed an high-fat diet (HFD, Control), HFD supplemented with CSNs, HFD together with voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. WAT, white adipose tissue. The values represent the means ± SE (n = 7–8). *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 2.

CSN supplementation with exercise additively increased energy expenditure. A: food intake. B: locomotive activity. C: running distance. D: oxygen consumption. E: fat oxidation of C57BL/6J mice fed a HFD (Control), HFD supplemented with CSNs, HFD in addition to voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. The values represent the means ± SE (n = 7–8). *P < 0.05, **P < 0.01.

Fig. 3.

CSN supplementation with exercise improved HFD-induced liver steatosis. A: hematoxylin and eosin (H&E) liver staining. B–D: liver levels of total lipids (B), triglycerides (TGs; C); nonesterified fatty acid (NEFA; D). F: glutamic pyruvic transaminase (GPT) levels in the plasma of C57BL/6J mice. Mice were fed a HFD (control), HFD supplemented with CSNs, HFD together with voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. The values represent the means ± SE (n = 7–8). *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 4.

CSN supplementation with exercise decreased cell size in subcutaneous WAT. A: H&E staining of subcutaneous WAT. B: cell size of A (in × 10³ μm²). The sizes of 100 randomly chosen cells in representative H&E-stained slides (n = 5) were quantified by ImageJ (1.48v). Each dot represents a cell, and the horizontal bar is the group mean. C: mRNA expression levels of uncoupling protein-1 (Ucp-1), peroxisome proliferator-activated receptor gamma coactivator-1α (Pgc-1a), lipoprotein lipase (Lpl), and adiponectin (AdipQ) in the subcutaneous WAT of C57BL/6J mice fed a HFD (Control), HFD supplemented with CSNs (CSN), HFD together with voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. The values represent the means ± SE (n = 7–8). *P < 0.05.

Fig. 5.

CSN supplementation with exercise increased cAMP levels and protein kinase A (PKA) activity in brown adipose tissue (BAT). A: level of cyclic AMP (cAMP). B: PKA activity in the BAT of C57BL/6J mice fed a HFD (Control), HFD supplemented with CSNs, HFD together with voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. The values represent the means ± SE (n = 7–8). *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 6.

CSN supplementation with exercise increased fatty acid oxidation by activating the oxidative phosphorylation (OXPHOS) gene program in the gastrocnemius muscle. A: TG levels in the gastrocnemius muscle. B: mRNA expression levels of lipoprotein lipase (Lpl), acyl-CoA oxidase (Aco), cytochrome c oxidase-1 (Cox-1), medium-chain acyl dehydrogenase (Mcad), and myosin heavy chain-1/β (Mhc-1/β) in the gastrocnemius muscle. C: fatty acid oxidation rate in the gastrocnemius muscle of C57BL/6J mice fed a HFD (Control), HFD supplemented with CSNs (CSN), HFD together with voluntary exercise (Exercise), or HFD supplemented with CSNs in addition to voluntary exercise (Exercise + CSN) for 56 days. The values represent the means ± SE (n = 7–8). *P < 0.05, **P < 0.01, ***P < 0.001.