[Frontiers in Bioscience S3, 352-371, January 1, 2011]

Physiological importance and control of non-shivering facultative thermogenesis

J. Enrique Silva

Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baystate Medical Center and Pioneer Valley Life Sciences Institute, Western Campus Tufts University School of Medicine, Springfield, Massachusetts, 01199


1. Abstract
2. Introduction
3. Evolutionary aspects
4. The major mechanisms of temperature homeostasis
5. Cold adaptation
5.1. Hormonal control of obligatory thermogenesis and basal metabolic rate
5.2. Bat thermogenesis.
5.2.1. Role of adrenergic stimulation on bat thermogenesis
5.2.2. Role of thyroid hormone on bat thermogenesis
5.3. Hormonal regulation of the ucp1 gene expression
5.4. Other effects of thyroid hormone on responsiveness to sympathetic stimulation
6. Role of d2 as master switch for bat thermogenesis in response to energy availability, overall temperature homeostasis and other physiological needs
7. Interrelation between obligatory thermogenesis and facultative thermogenesis, and role of neuro-hormonal signals
8. Concluding remarks
9. Acknowledgments
10. References


This review examines general and evolutionary aspects of temperature homeostasis, focusing on mammalian facultative or adaptive thermogenesis and its control by the sympathetic nervous system and hormones. Thyroid hormone acquired a new role with the advent of homeothermy enhancing facultative thermogenesis by interacting synergistically with the sympathetic nervous system, and directly increasing basal metabolic rate (obligatory thermogenesis). Facultative thermogenesis is triggered by cold. The major site of facultative thermogenesis in mammals is brown adipose tissue, endowed with abundant mitochondria rich in a protein called uncoupling protein-1. This protein can uncouple phosphorylation in a controlled manner, releasing the energy of the proton-motive force as heat. Its synthesis and function are regulated synergistically by the sympathetic nervous system and thyroid hormone and modulated by other hormones directly, or indirectly, modulating sympathetic activity as well as thyroid hormone secretion and activation in brown adipose tissue. Alternate, evolutionary older forms of facultative thermogenesis activated in transgenic mice with disabled brown adipose tissue thermogenesis reveal this latter as the culmination of energy-efficient facultative thermogenesis.