Fat and Energy Economy in Hypo- and Hyperthyroidism Are Not the Mirror Image of One Another

That thyroid hormone (TH) stimulates the rate of metabolism and heat production has been known for over a century. Adolf Magnus-Levy, a German physician and physiologist, asked in 1895 a very insightful question that today may seem trivial, namely whether the changes in weight observed in hyperand hypothyroid patients in disproportion to food intake had anything to do with metabolism. He and his mentor, Carl von Noorden, had developed the conceptual bases and the technology to measure metabolism, i.e. the rate of oxidations in the body. Seemingly, von Noorden’s interest in the thyroid was less than Magnus-Levy’s, so this latter took upon himself the studies that he published in a three-page article (1) of the Berlin Clinical Journal. He reported that both oxygen consumption (VO2) and carbon dioxide production were increased in patients with hyperthyroidism, that the abnormalities disappeared when the condition was cured, and that he could reproduce in healthy subjects the abnormalities observed in thyrotoxic patients when given thyroid extract for a few weeks. Of interest to the discussion that follows, the respiratory exchange ratio (RER) or respiratory quotient was reduced by TH. More than a century has gone by, yet we still cannot pinpoint the mechanisms whereby TH causes such changes in metabolism, although we have a better appreciation of the biological meaning and its impact in evolution. The article by Klieverik et al. (2) in this issue makes several points that significantly add to our understanding as to how TH influences energy economy in whole animals and raises concepts of potential value to understand energy balance and deal with the pandemic of obesity. Living systems are open, in a free exchange of energy with the environment. Through millions of years of evolution during which food has never been as readily available as it is now, species selected efficient mechanisms to seek and obtain food and to conserve energy. In this regard, the advent of homeothermy imposed a big challenge by forcing homeothermic species to consume more energy to just burn it and produce heat, essential to maintain the set core temperature ( 37 C) in environments usually cooler, particularly in latitudes far from the equator. Comparisons between poikilothermic and homeothermic species under strictly controlled conditions have shown that warm-blooded animals spend much more energy, whether as a whole or tissue by tissue (3). Furthermore, whether one looks at the energy cost of biochemical or physiological activities, this is higher in warm-blooded animals, indicating that the energy cost of living is higher in these species and that thermodynamic efficiency is reduced for the sake of producing heat (4). A large body of evidence indicates that TH is largely responsible for these differences between poikilothermic and homeothermic species. Furthermore, amphibian metamorphosis, a THdependent process, it is an energy-costly process, markedly accelerated by TH (5), yet the energy cost of bringing this process rapidly to an end is much less than resting energy expenditure (REE) of a comparable size mammal (6). Likewise, for any given amount of mechanical work, heat production is markedly greater in euthyroid than hypothyroid skeletal muscle (7). So, TH increases the energy cost of living, and the difference is largely accounted for by energy that is simply dissipated as heat for the sake of temperature homeostasis.