Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats

Abstract

The role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.

The effect of estrogen on brown adipose tissue activity in male rats

“…Estrogen or vehicle was administered either peripherally (via IP injection, vehicle = sesame oil), or centrally (via ICV injection, vehicle = saline + 10% DMSO). These protocols have been used previously [ 18 ] and are described briefly here.…”

“…Control temperature, heart rate and MAP data were compared to data from Van Schaik et al [ 18 ]. No differences were identified between the two studies for any metrics (Additional file 1 : Table S1).…”

“…Given the differences that have been identified in the baseline conditions of our cardiovascular data, control data were compared to previously published work that used similar protocols [ 18 ]. Different vehicles were used as Van Schaik et al [ 18 ] used saline for both IV and ICV injection, while this study used sesame oil by IP injection and 10% DMSO for ICV injection. No significant differences were found in the mean changes in the control temperature, heart rate or MAP between the two studies (Additional file 1 : Table S1).…”

“…These coincident observations raise the possibility that increases in iBAT temperature are secondary to the core temperature increase, and not the other way around. Although it is possible to separate evoked thermogenic response from core temperature changes [ 18 ] by assessing cFos expression in known thermogenic central neural circuits. Unfortunately, we were unable to assess activation of specific nuclei by cFos expression due to tissue quality problems leaving insufficient samples for statistical analysis (n = 3).…”

“…Differences in MAP between groups, at baseline, is one limitation of the present study. This series of experiments were performed in parallel with another, published set of experiments [ 18 ], following identical procedures where no significant differences were observed among baseline conditions. Further, control data obtained from experiments, during post-intervention observational period was comparable between the two studies (Additional file 1 : Table S1).…”