Abstract
Adrenaline and noradrenaline, the main effectors of the sympathetic nervous system and adrenal medulla, respectively, are thought to control adiposity and energy balance through several mechanisms. They promote catabolism of triglycerides and glycogen1, stimulate food intake when injected into the central nervous system2, activate thermogenesis in brown adipose tissue3,4, and regulate heat loss through modulation of peripheral vasoconstriction and piloerection1. Thermogenesis in brown adipose tissue occurs in response to cold and overeating (diet induced)5-7, and there is an inverse relationship between diet-induced thermogenesis and obesity both in humans8 and in animal models9-12 . As a potential model for obesity, we generated mice that cannot synthesize noradrenaline or adrenaline by inactivating the gene that encodes dopamine β-hydroxylase. These mice are cold intolerant because they have impaired peripheral vasoconstriction and are unable to induce thermogenesis in brown adipose tissue through uncoupling protein (UCP1). The mutants have increased food intake but do not become obese because their basal metabolic rate is also elevated. The unexpected increase in basal metabolic rate is not due to hyperthyroidism, compensation by the widely expressed uncoupling protein UCP2, or shivering.
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Thomas, S., Palmiter, R. Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387, 94–97 (1997). https://doi.org/10.1038/387094a0
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DOI: https://doi.org/10.1038/387094a0
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