Recruited brown adipose tissue as an antiobesity agent in humans

Abstract

Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

Horizons in the Pharmacotherapy of Obesity

“…They were ineffective in reducing body fat in a 6-week study [87], but reduced abdominal fat in a 12-week study [89].…”

“…Some fat loss was observed in a 6-week study [87]. However, skeletal muscle made a far greater contribution that brown adipose tissue to systemic glucose uptake in response to cold [88], raising the possibility that skeletal muscle might also make a greater contribution to coldstimulated thermogenesis.…”

Surgical injury induces local and distant adipose tissue browning

“…30,31 As a result, promotion of BAT (through an increase in BAT mass or turning WAT into BAT) is increasingly acknowledged as a potential therapeutic strategy for obesity and obesity related diseases. 4,6,27,29,32 Importantly, these data evidence remarkably rapid (one day) adipose tissue browning. Surgical injury leads to a 12-fold induction of UCP1 transcript after one day, which can be compared to the 9-fold induction in the same strain mice acclimated to 5 C cold for 4 weeks 33 or the 2.5 fold induction after 2 weeks of treadmill exercise in BALB/C mice.…”

“…4,27 In mice, both activation and transplantation of BAT were shown to improve whole body metabolism and insulin sensitivity. 1,29 Furthermore, human white adipocytes can be manipulated in vitro to develop "brown" characteristics (UCP1 expression) by forced adenoviral overexpression of PGC1a.…”

“…3) Under physiological conditions, cold exposure is the most powerful stimulus for BAT activation. 27 To evaluate the contribution of weight loss and reduced body temperature associated with the observed browning phenomenon, we subjected mice to a 3-day glucose-water-only regimen (caloric restriction, CR) 28 before the procedure. Here, Mice on CR consumed less calories (except on the post operative day), lost weight, and had a lower body temperature (Fig.…”