Can Caffeine, Ephedrine and Norepinephrine Activate Your Brown Fat? An Experimental Study on the Groups of Lean and Obese LA/Ntul//-cp Rats

Brown adipose tissue occurs in man and mammalian animals, where it is innervated by the sympathetic nervous system and is readily activated by adrenergic stimulation, and where once activated results in significant increases in thermogenic activity. 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 ?- agonist epinephrine were examined. Caffeine (CAF) resulted in a 33% increase in VO2, ephedrine (EPH) a 48% increase, the combination CAF+EPH a 53% increase, and the EPI a 33% increase in VO2. 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 EPI treatment. These findings support a strong CAF-stimulated thermogenic response in both the lean and obese phenotypes of the congenic LA/Ntul/-cp rat, a response that was qualitatively similar to that of NE and that was further enhanced by EPH alone or in conjunction with CAF. Although the pharmacologic and physiological mechanisms elicited by the three agents under study may have different mechanisms of action, the results show that they are complementary in nature in increasing nonshivering thermogenesis parameters and, consequently, metabolic energy expenditure in both lean and obese rats. In conclusion, while caffeine as monotherapy may bring about limited weight loss in humans and other mammalian organisams, 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. Thus, a case may be made for the role of caffeine and adrenergic agents on increasing the parameters of energy expenditure and may contribute to energy balance in man and animals.