Mammalian cellular machinery has evolved to function best at ~37 °C, making maintenance of core body temperature (at ~37 °C) critical for optimal organ function. The physiological importance of thermoregulation has been appreciated for many years, but our mechanistic understanding of the diversity and functioning of thermogenic mechanisms has advanced considerably in the past century. A brief analysis by Prusiner and Poe (published in 1968) marked a pivotal shift in thermoregulation research, transitioning from a coarse physiological perspective to biochemical interpretations of thermogenic pathways.

In the thermoneutral zone, core body temperature is sustained with minimal metabolic effort, facilitated by anatomical features and baseline metabolism. The thermoneutral zone is a subjective temperature range that might be around 20–22 °C for a lean, lightly clothed man. When environmental temperatures drop below the thermoneutral zone, the body activates a series of thermoregulatory mechanisms to preserve core temperature and re-establish thermal homeostasis. Physiologically, thermogenic mechanisms are classified as shivering thermogenesis, which occurs in muscle, and non-shivering thermogenesis (NST). NST comprises a group of processes that use different energy sources and mechanisms that ultimately converge in the release of heat. Prusiner and Poe distinguished the molecular mechanisms of thermogenic pathways and proposed a classification scheme based on the biochemical origins of metabolic heat rather than a one based on physiology. In addition, several other suggestions presented in their paper have had lasting implications for ongoing research on futile cycles and thermogenesis. Specifically, the authors highlighted two points that remain relevant for contemporary studies: first, the relative thermogenic contribution of ATP synthesis versus ATP hydrolysis, and second, the thermogenic role of the ATP-consuming futile cycle.

哺乳动物细胞机制已经进化到在 ~37 °C 时功能最佳，因此维持核心体温 （~37 °C） 对于最佳器官功能至关重要。多年来，人们一直认识到体温调节的生理重要性，但我们对产热机制的多样性和功能的机械理解在上个世纪取得了长足的进步。Prusiner 和 Poe 的简要分析（1968 年出版）标志着体温调节研究的关键转变，从粗略的生理学角度过渡到生热途径的生化解释。

在热中性区，核心体温以最小的代谢努力维持，这得益于解剖学特征和基线代谢。热中性区是一个主观温度范围，对于一个瘦弱、穿着轻便的男人来说，可能在 20-22 °C 左右。当环境温度降至热中性区以下时，身体会激活一系列体温调节机制，以保持核心温度并重新建立热稳态。在生理学上，产热机制分为发生在肌肉中的颤抖产热和非颤抖产热 （NST）。NST 由一组使用不同能源和机制的过程组成，这些过程最终会聚集成热量的释放。Prusiner 和 Poe 区分了产热途径的分子机制，并提出了一种基于代谢热的生化起源的分类方案，而不是基于生理学的分类方案。此外，他们论文中提出的其他几项建议对正在进行的徒劳循环和产热研究产生了持久的影响。具体来说，作者强调了与当代研究相关的两点：第一，ATP 合成与 ATP 水解的相对产热贡献，第二，消耗 ATP 的徒劳循环的产热作用。