UCP1: its involvement and utility in obesity

Abstract

Energy balance to prevent the development of obesity is dependent on energy expenditure. Although physical activity is the dominant mechanism for dissipating excess energy, a system of thermogenesis that evolved to protect the body from hypothermia is based upon the uncoupling of oxidative phosphorylation in brown adipocytes by the mitochondrial uncoupling protein (UCP1). It has been shown that upregulation of UCP1 by genetic manipulations or pharmacological agents can reduce obesity and improve insulin sensitivity. Recent evidence has shown the existence of two sources for brown adipocytes, one appearing as discrete brown fat depots during fetal development and the other appears during post-natal development as diffuse populations in traditional white fat depots. The latter can be induced by adrenergic stimulation depending on the genetic background of the animals and the nutritional environment. Understanding the biological and environmental factors controlling the expression of these two brown adipocyte populations promises to provide new strategies by which enhanced thermogenesis can be used to reduce obesity.International Journal of Obesity (2008) 32, S32-S38; doi:10.1038/ijo.2008.236.

Figure 1

Sites of genetic variation in the signaling and transcription factors associated with induction of Ucp1 in retroperitoneal fat depots. The ratio in expression between expression in A/J versus C57BL/6 J mice is shown in blue. The analysis suggests that the synergy among several regulatory sites with modest differences in expression leads to the 80-fold ratio in the level of Ucp1 expression.

Figure 2

Developmental profiles illustrating the appearance of brown adipocytes in interscapular brown adipose tissue (iBAT) initially at about 4 days before birth. Although the inguinal fat depot (ING) first appears at birth, but the visceral fat (VAT) not until ∼ 10 days of age, brown adipocytes appear in both depots between 15 and 30 days of age. The induction of brown adipocyte at 20 days of age is higher in A/J than C57Bl/6J (B6) mice and is induced in adult animals by adrenergic stimulation in A/J mice, but not B6 mice. This genetic difference in the induction of brown adipocytes among white fat depots is not found in iBAT. This figure has been modified from Xue et al., courtesy of Nina Laidlaw.