Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

Abstract

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

Recruited brown adipose tissue as an antiobesity agent in humans

“…Ono et al reported that prolonged treatment of rats with capsinoids resulted in increased UCP1 expression and decreased body fat (14). Body fat reduction and increased EE were also shown after capsinoid treatment for 12 weeks in mildly obese human subjects (20).…”

“…To explore more practical methods for the recruitment of BAT, we focused on the chemical stimulants of TRP channels, particularly capsinoids. Because capsinoids activate TRPV1 and TRPA1 (13) and increase BAT thermogenesis (14,19), we reasoned that long-term capsinoid treatment could possibly recruit BAT in humans, as chronic cold exposure does.…”

“…It is known that the stimulatory effects of cold on BAT are mediated through the activation of the sympathetic nervous system, initiated by peripheral stimulation of transient receptor potential (TRP) channels in sensory neurons (8,12). This pathway is also activated by some food ingredients, such as capsaicin and capsinoids, nonpungent capsaicin analogs (13,14). Stimulation of TRP channels by capsinoids is effective for enhancement of BAT thermogenesis and upregulation of uncoupling protein 1 (UCP1), a key molecule of BAT thermogenesis, in mice (14).…”

“…This pathway is also activated by some food ingredients, such as capsaicin and capsinoids, nonpungent capsaicin analogs (13,14). Stimulation of TRP channels by capsinoids is effective for enhancement of BAT thermogenesis and upregulation of uncoupling protein 1 (UCP1), a key molecule of BAT thermogenesis, in mice (14).…”

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

“…In adult humans, a 4-wk treatment with CSNs was found to increase oxygen consumption, and a 12-wk treatment decreased the abdominal fat mass in subjects with body mass indexes (BMIs) of 25-35 (15, 50). Mechanistically, oral CSN supplements have been reported to activate transient receptor potential vanilloid subtype 1 (TRPV1) in the gut (14,47), resulting in increased sympathetic efferent activity and thermogenesis (41). Activation of TRPV1 signaling has been reported to positively regulate exercise endurance and energy expenditure in mice (30).…”