Article

Regulation of Energy Balance and Body Weight by the Brain: A Distributed System Prone to Disruption

Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19104, USA.
The Psychiatric clinics of North America (Impact Factor: 1.87). 12/2011; 34(4):733-45. DOI: 10.1016/j.psc.2011.08.008
Source: PubMed

ABSTRACT

Maintaining adequate energy supply via regulation of food intake and energy expenditure is crucial for survival and reproduction. The neural control of energy balance is highly complex, occurs across distributed central and peripheral areas, and incorporates multiple domains of control (including homeostatic and hedonic processes). The sheer number of active compounds (such as leptin and GLP-1) involved in the regulation of food intake speaks to the redundancy and complexity of the system. The balance between energy intake and expenditure is under CNS control. Constant bidirectional communication between the brain and the GI tract, as well as between the brain and other relevant tissues (ie, adipose tissue, pancreas, and liver), ensures that the brain constantly perceives and responds accordingly to the energy status/needs of the body. This elegant biological system is subject to disruption by a toxic obesogenic environment, leading to syndromes such as leptin and insulin resistance, and ultimately further exposing obese individuals to further weight gain and T2DM. Recent imaging studies in humans are beginning to examine the influence that higher-order/hedonic brain regions have on homeostatic areas, as well as their responsiveness to homeostatic peripheral signals. With greater understanding of these mechanisms, the field moves closer to understanding and eventually treating the causalities of obesity.

Full-text preview

Available from: ncbi.nlm.nih.gov
  • Source
    • "Thus, in a physiological situation, the impact of ghrelin is distributed over many sites in the brain which likely act in concert. The concept of a hormone or a neuropeptide acting on many distributed sites in the brain from which it can elicit a similar outcome, for example a change in food intake, is not novel and has already being proposed and evaluated for leptin and melanocortin (Grill, 2006; Leinninger et al., 2009; Skibicka and Grill, 2009; Faulconbridge and Hayes, 2011). Food deprivation is associated with high levels of circulating ghrelin. "

    Full-text · Dataset · Sep 2014
  • Source
    • "Thus, in a physiological situation, the impact of ghrelin is distributed over many sites in the brain which likely act in concert. The concept of a hormone or a neuropeptide acting on many distributed sites in the brain from which it can elicit a similar outcome, for example a change in food intake, is not novel and has already being proposed and evaluated for leptin and melanocortin (Grill, 2006; Leinninger et al., 2009; Skibicka and Grill, 2009; Faulconbridge and Hayes, 2011). Food deprivation is associated with high levels of circulating ghrelin. "

    Full-text · Dataset · Sep 2014
  • Source
    • "Eating behavior can be modeled into a homeostatic part, signals from the body to the brain reflecting the need for energy, and a hedonic part, our pleasure while eating that is mostly independent of energy requirements (10). There is conflicting data as to whether GLP-1 analogs induce their effect on reduction in energy intake by influencing only the homeostatic component of hunger or by influencing the hedonic part as well (21,22). "
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE Glucagon-like peptide-1 receptor agonists like exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between "responders" (reduction in energy intake after exenatide infusion) and "nonresponders."RESEARCH DESIGN AND METHODS We performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain.RESULTSResponders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness.CONCLUSIONS Our results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.
    Full-text · Article · Mar 2013 · Diabetes care
Show more