We have studied the effects of chronic peripheral infusion of thyrotropin releasing hormone (TRH) and norepinephrine (NE) alone and together. Do these hormones additively affect energy balance and body weight similarly in lean and obese animals? 20 each lean Wistar and obese (fa/fa) Zucker strain rats were studied. Food intake, body weight and resting metabolic rate (RMR) were measured over a 14 day period. We confirmed that in the obese animals, separately the hormones act as in the lean: NE stimulated RMR, but with parallel stimulation of appetite so that weight gain continued; TRH stimulated RMR but inhibited food intake so that rate of weight gain was reduced. TRH and NE together acted to further enhance RMR, but the inhibitory and stimulatory effects on food intake cancelled out. Thus a negative energy balance resulted in both groups; however, resultant weight loss was profound in lean but only moderate in obese. We suggest that the relative insensitivity of the obese to TRH and NE together reflects the inability of their brown adipose tissue to respond to thermogenic agents, even when chronically administered.

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