Application—A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis in vivo

A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis in vivo

   Brown adipose tissue (BAT) has received renewed interest for its potential to reduce adiposity and improve metabolic health. While BAT was traditionally considered to be lost after infancy, recent evidence supports the presence of functional BAT in adult humans. BAT is unique in its expression of uncoupling protein-1 (UCP1), which is activated by cold and b-adrenergic signaling as a means to maintain core body temperature in cold environments. When activated, UCP1 facilitates proton leak across the mitochondrial inner membrane to dissociate oxygen uptake from ATP synthesis and generates large amounts of heat.

   Therefore non-invasive, objective assessments of BAT activity have become increasingly necessary to determine whether adipose tissue thermogenic capacity has been altered by various interventions in pre-clinical rodent models. Several nuclear imaging methods have been employed to measure BAT activity in rodents. However, these methods rely on the assumption that circulating substrate uptake or blood flow reflects BAT activity. Since thermal energy is a specific end product of UCP1- mediated metabolism in BAT, its detection is an ideal surrogate of BAT activity. Several studies have measured surface body temperature using infrared imaging in rodents as an analog to BAT activity under basal or stimulated conditions. Therefore, we chose to test whether surface body temperature assessed using infrared thermography accurately reflects changes in BAT activity in vivo when challenged with the highly specific b3-adrenoreceptor agonist.

Figure 1. Representative infrared images of Ucp1þ/þ and Ucp1 mice following the two separate treatments.

   The present results demonstrate for the first time that stimulated dorsal surface temperature represents an accurate determination of UCP1-mediated thermogenesis. Further, the described analysis of thermal images can be done quickly, is relatively low cost, and does not require highly trained personnel as compared with nuclear imaging. In addition, compared with FDG-PET there is no radiation, which allows sequential and more frequent measurements in the same animal. In the future it will be necessary to compare thermal imaging with other methods used to detect BAT activity following different metabolic stimuli.

Figure 2. Representative infrared images of each ambient temperature group after saline or CL- 316,243 injection.

   Brown adipose tissue holds an enormous potential to improve metabolic health. In order to more accurately determine the capacity for BAT activation, we have validated the use of infrared thermography as a means to rapidly assess BAT-derived thermogenesis. These findings represent the first standardized method utilizing infrared imaging to specifically detect UCP1 activity in vivo.

Reference

Justin D. Crane, Emilio P. Mottillo, Troy H. Farncombe, et al. A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis in vivo. Molecular Metabolism. 1-5, 2014.