Can caffeine activate your brown fat? Effects of caffeine, ephedrine, and norepinephrine on nonshivering thermogenesis in congenic lean and obese LA/Ntul//-cp rats

To determine the effects of norepinephrine (NE) or of caffeine (CAF) alone or in combination with ephedrine (EPH) were determined in groups of lean and obese LA/Ntul//-cp Rats, Body weights of obese were >> lean littermates (p=<0.01) and measures of RMR of lean > Obese (p=<0.05). The effects of caffeine, ephedrine, a caffeine+ephedrine combo, and the β- agonist epinephrine was examined. Caffeine (CAF) resulted in a 33% increase in VO2, ‘nonephedrine’ (EPH) a 48% increase, the combination CAF+EPH a 53% increase, and the NE a 33% increase in VO2. In obese rats, the increases in VO2 were of a similar percentage (21 vs 48 vs 47 % vs 31% for CAF, EPH, CAF+EPH and NE respectively although the peak responses attained in the obese tended to be of a significantly lesser absolute magnitude than were observed in the lean phenotype. The time to peak thermogenic response was similar in lean and obese phenotypes for each of the 4 treatment regimens, but the duration of the peak responses to each treatment differed between lean and obese phenotypes (Obese > lean) for CAF, EPH and the CAF+EPH combination but duration of the VO2 response was similar in both phenotypes for the NE treatment. Thus, these observations are consistent with a significant CAF-stimulated thermogenic response that was qualitatively similar to that of NE in both lean and obese phenotypes of the congenic LA/Ntul//-cp rat and which thermogenic responses were further augmented with EPH alone or in combination with CAF. Although the mechanisms of action of the pharmacologic and physiologic mechanisms elicited may differ among the three agents studied the results indicate that they are complimentary in nature in bringing about increases in parameters of nonshivering thermogenesis and thus increasing metabolic energy expenditure in both lean and obese rats. In conclusion, while caffeine as monotherapy may bring about limited weight loss, the combination of caffeine plus ephedrine was more effective in the lean and obese phenotypes of the congenic, non-diabetic LA/Ntul//-cp (Corpulent) rat.