Impact of Exercise and Detraining during Childhood on Brown Adipose Tissue Whitening in Obesity

Abstract

This study aimed to investigate the influence of childhood exercise and detraining on brown adipose tissue (BAT) whitening in obesity. Four-week-old male Long-Evans Tokushima Otsuka (LETO) rats (n = 9) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 24) were used as non-obese and obese animals, respectively. OLETF rats were divided into non-exercise sedentary (n = 9) and exercise groups. OLETF rats in the exercise group were further divided into subgroups according to the exercise period—exercise from 10- to 12-weeks-old (n = 6); and exercise from 4- to 6-weeks-old, and detraining from 6- to 12-weeks-old (n = 9). At 12-weeks-old, immediately after exercise period, BAT whitening in OLETF rats was inhibited by exercise despite the fact that hypertrophy was not caused in the plantaris muscle. However, the effectiveness was attenuated during the detraining period. Histological BAT whitening and downregulation of uncoupling protein-1 (UCP-1) were found in non-exercise sedentary OLETF rats at 12-weeks-old. The downregulation was not inhibited, even though exercise histologically inhibited BAT whitening in OLETF rats. Childhood exercise decreased BAT whitening in obesity. Detraining attenuated the inhibition of BAT whitening. These results suggest that regular exercise is needed to improve BAT whitening and downregulation of UCP-1 in obesity.

Detraining after short‐term exercise induces hyperphagia and obesity with fatty liver and brown adipose tissue whitening in young male OLETF rats

“…In the present study, because all rats were fed a standard diet containing high carbohydrate content, hyperphagia during the detraining period could result in excess fat accumulation, particularly in the liver but not in the pancreas and skeletal muscle. Unlike fatty pancreas and intramuscular fat, BAT whitening induced by a high‐fat diet and a standard diet has been observed in obese models (Ku et al., 2016; Takaishi et al., 2021). BAT whitening is closely associated with capillary density.…”

Adipose tissue browning and thermogenesis under physiologically energetic challenges: a remodelled thermogenic system

“…Thermoneutrality. In contrast to the aforementioned high energetic challenges leading to adipose tissue browning, the whitening process is dominated by mitigation of energetic challenges, including a thermoneutral environment (Cui et al, 2016;Kotzbeck et al, 2018), excess energy intake (Lopez-Vicchi et al, 2022;Miranda et al, 2020) and physical inactivity (Nguyen et al, 2022;Takaishi et al, 2021). Ambient temperature is a fundamental factor that directly determines heat production; thermoneutrality reduces the energy cost required for maintaining body temperature, thus alleviating energetic challenges.…”

“…In OLETF rats, childhood exercise had an immediate inhibitory effect on BAT whitening and UCP1 downregulation induced by obesity. However, the inhibitory effect was diminished after detraining, and the density of unilocular white adipocytes did not differ between the sedentary and exercise group following 6 weeks of detraining (Takaishi et al., 2021). Similarly, detraining increased adipocyte size and lipid accumulation, but exercise in early childhood efficiently mitigated BAT whitening and decreased food consumption until adulthood (Nguyen et al., 2022).…”

Quantitative assessment of brown adipose tissue whitening in a high-fat-diet murine model using synthetic magnetic resonance imaging

“…High-fat diet (HFD) is a well-known obesity-inducing factor; obese mice can gradually transform BAT into WAT through a process called BAT whitening. Different characteristic changes, such as large lipid droplet accumulation, mitochondrial dysfunction or loss, decreased UCP1 expression and vascular endothelial growth factor (VEGF), as well as tissue inflammation [ [3] , [4] , [5] ], can be induced by BAT whitening, resulting in excess ectopic fat accumulation, which is a major risk factor for developing hyperlipidemia, type 2 diabetes, and cardiovascular diseases [ 6 ]. Moreover, BAT whitening may store more triglycerides and reduce energy expenditure to induce or even aggravate obesity and associated metabolic disorders [ 1 , 2 ].…”