A temperature hypothesis of hypothalamus-driven obesity

Abstract

Obesity is a metabolic state in which excess fat is accumulated in peripheral tissues, including the white adipose tissue, muscle, and liver. Sustained obesity has profound consequences on one's life, which can span from superficial psychological symptoms to serious co-morbidities that may dramatically diminish both the quality and length of life. Obesity and related metabolic disorders account for the largest financial burden on the health care system. Together, these issues make it imperative that obesity be cured or prevented. Despite the increasing wealth of knowledge on the etiology of obesity (see below), there is no successful medical strategy that is available for the vast majority of patients. We suggest that brain temperature control may be a crucial component in obesity development and that shortcutting the brain metabolic centers by hypothalamic temperature alterations in a non-invasive remote manner will provide a revolutionary approach to the treatment of obesity.

Keywords: circuit activity; hypothalamus; obesity; temperature regulation.

Figure 1

Schematic drawing showing known interactions and projection targets of various hypothalamic peptidergic systems, including lateral hypothalamic neurons producing hypocretin/orexin (Hcrt) and melanin concentrating hormone (MCH) and components of the melanocortin system, the NPY/AGRP- and MSH-producing neurons. These neuronal populations are targeted from the circulation by white adipose tissue-derived leptin and stomach-derived ghrelin. They are synaptically interconnected and project, to some degree, in an overlapping manner to intra- and extra-hypothalamic sites. It is a recurring mistake to consider peptide circuits as independent entities. Almost without exception, peptidergic neurons contain various other neuromodulators, including the classical neurotransmitters GABA or glutamate (Glut). With varying artistic characteristics, most of the schemes proposed to date are similar to Figure 1 in that they depict connectivity as a still picture implying hard wiring. While such mapping of connectivity will continue to provide important building blocks for evolving concepts, they lack both synaptic resolution as well as indication of soft wiring or plasticity.