Research highlights from the literature

Abstract

Obesity, a disorder reaching epidemic proportions, is the result of dietary intake that exceeds energy expenditure. There is a complex relationship between the sympathetic nervous system and obesity, with interactions in the central nervous system and peripheral tissues (for review see Esler et al. (2001) Am J Hyperten 14:304S–309S). The following are recent publications that highlight the complexities of this interaction. An increase in dietary intake triggers compensatory mechanisms that signal the brain to reduce appetite and peripheral organs to increase energy expenditure (“diet-induced thermogenesis”),presumably by activation of β-adrenoreceptors. Of particular interest has been the role of β3-adrenoreceptors, which may play a role in obesity. However, gene knock-out mice lacking β3adrenoreceptors do not develop significant obesity. Because other receptor subtypes may compensate when the function of one is eliminated, Bachman et al. cross-bred mice to lack all three β-adrenoreceptor subtypes (“β-less mice”). On a regular diet, β-less mice had a reduced metabolic rate and were slightly obese. On a high-fat diet, βless mice developed massive obesity that was entirely due to absence of diet-induced thermogenesis. These findings indicate that the sympathetic nervous system, acting through β-adrenoreceptors, is essential for diet-induced thermogenesis, and that this pathway plays a critical role in the body’s defense against obesity induced by excess intake. Catecholamines act on fat cells to promote lipolysis, resulting in the release of free fatty acids (nonesterified fatty acids, NEFA) and glycerol. The in vivo importance of this effect in humans is not completely understood. Patel et al. hypothesized that sympathetic activity to fat tissue is increased during fasting, and may explain the increase in lipolysis seen in that state. They infused tritiated norepinephrine systemically, while sampling venous effluent draining abdominal subcutaneous tissue, before and after a 72 hour fast. Fasting did not alter total body or forearm norepinephrine spillover, but increased abdominal subcutaneous spillover. Thus, the body may adapt to starvation in part by selectively increasing sympathetic activity to adipose tissue, which results in mobilization of energy from adipose stores. It would be of interest to determine whether this mechanism differs between lean and obese individuals. Leptin has received much attention as a peptide regulating appetite. Corticotropin-releasing hormone (CRH) is another peptide that acts in the hypothalamus to reduce appetite and, by inducing sympathetic activation, increase energy expenditure. Urocortin (UCN), a neuropeptide closely related to CRH (45 % sequence identity) which acts on CRH receptors, also acts in the hypothalamus to decrease appetite. De Fanti and Martinez examined whether central UCN also increases energy expenditure. Intracerebroventrical injection of UCN in male Wistar rats significantly increased whole body oxygen consumption. It also increased core temperature, an effect that was prevented once autonomic function was eliminated by the ganglionic blocker chlorisondamine. These studies suggest that UCN acts centrally to activate sympathetic tone, resulting in an increase in energy expenditure. It should be noted that different investigators found opposite results in mice, suggesting possible species differences.Which animal model replicates human physiology remains to be determined.