Kanter, R. We're not alone coping with the cold. http://environmentalalmanac.blogspot.ca/2014/02/were-not-alone-coping-with-cold.html (accessed 26 Nov 2014)
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The Big Picture...
Thorough understanding of the UCP1-mediated thermogenic pathway and its regulation can impact the development of novel therapies to combat obesity. In animals, thermogenesis is used mainly for heat production in cold environments. Animals like the Richardson’s ground squirrel prepare for winter by increasing their food intake and storing the excess food in brown adipocytes. As they are aroused from hibernation in spring, or as they become cold-acclimatized, thermogenic activity increases as the animal tries to maintain its body temperature for essential metabolic processes.
In humans, BAT thermogenesis is mainly used for heat production during early infancy, and its thermogenic activity decreases as humans age. Since non-shivering thermogenesis is less relied upon for heat production past infancy, stimulating this type of thermogenesis could potentially be used in weight loss. Studies have shown that there is a negative correlation between BAT content and BMI, as such, potential compounds that increase thermogenic capacity or content could be developed as a solution for weight loss. Novel drugs like Miglitol that increase energy expenditure are essential and they may become useful in the future development of new classes of weight loss agents that target the βAR-cAMP-PKA pathway in human peripheral tissues. Currently, drugs such as 2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) promote uncoupling of the ETC to oxidative phosphorylation to induce thermogenesis.
In addition to developing pharmacological agents that induce thermogenesis, gene therapy can also be used to induce thermogenesis by targeting genes that are activated by the βAR-cAMP-PKA pathway. We could target genes like CREB and Ppargc1a that upregulate expression of Ucp1 and induce thermogenesis. More research has to be done on the mechanisms behind BAT thermogenesis in humans and how thermogenesis increases energy expenditure.
Overall, these findings emphasize the potential for the development of weight loss agents for humans by upregulating brown fat thermogenesis through the action of the UCP1 protein.
References
Primary Articles:
1. Matthias, A.; Ohlson, K. B.; Fredriksson, J. M.; Jacobsson, A.; Nedergaard, J.; Cannon, B. Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis. J. Biol. Chem. 2000, 275, 25073-25081.
2. Milner, R. E.; Wang, L. C.; Trayhurn, P. Brown fat thermogenesis during hibernation and arousal in Richardson's ground squirrel. Am. J. Physiol. 1989, 256, R42-8.
3. Sasaki, T.; Shimpuku, M.; Kitazumi, T.; Hiraga, H.; Nakagawa, Y.; Shibata, H.; Okamatsu-Ogura, Y.; Kikuchi, O.; Kim, H. J.; Fujita, Y.; Maruyama, J.; Susanti, V. Y.; Yokota-Hashimoto, H.; Kobayashi, M.; Saito, M.; Kitamura, T. Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates. Endocr. J. 2013, 60, 1117-1129.
4. Vijgen, G. H.; Bouvy, N. D.; Teule, G. J.; Brans, B.; Schrauwen, P.; van Marken Lichtenbelt, W. D. Brown adipose tissue in morbidly obese subjects. PLoS One 2011, 6, e17247.
5. Zingaretti, M. C.; Crosta, F.; Vitali, A.; Guerrieri, M.; Frontini, A.; Cannon, B.; Nedergaard, J.; Cinti, S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009, 23, 3113-3120.
Picture of arctic squirrel was taken from http://environmentalalmanac.blogspot.ca/2014/02/were-not-alone-coping-with-cold.html
1. Matthias, A.; Ohlson, K. B.; Fredriksson, J. M.; Jacobsson, A.; Nedergaard, J.; Cannon, B. Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis. J. Biol. Chem. 2000, 275, 25073-25081.
2. Milner, R. E.; Wang, L. C.; Trayhurn, P. Brown fat thermogenesis during hibernation and arousal in Richardson's ground squirrel. Am. J. Physiol. 1989, 256, R42-8.
3. Sasaki, T.; Shimpuku, M.; Kitazumi, T.; Hiraga, H.; Nakagawa, Y.; Shibata, H.; Okamatsu-Ogura, Y.; Kikuchi, O.; Kim, H. J.; Fujita, Y.; Maruyama, J.; Susanti, V. Y.; Yokota-Hashimoto, H.; Kobayashi, M.; Saito, M.; Kitamura, T. Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates. Endocr. J. 2013, 60, 1117-1129.
4. Vijgen, G. H.; Bouvy, N. D.; Teule, G. J.; Brans, B.; Schrauwen, P.; van Marken Lichtenbelt, W. D. Brown adipose tissue in morbidly obese subjects. PLoS One 2011, 6, e17247.
5. Zingaretti, M. C.; Crosta, F.; Vitali, A.; Guerrieri, M.; Frontini, A.; Cannon, B.; Nedergaard, J.; Cinti, S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009, 23, 3113-3120.
Picture of arctic squirrel was taken from http://environmentalalmanac.blogspot.ca/2014/02/were-not-alone-coping-with-cold.html