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Neurobiology of Obesity Laboratory University of Manitoba

Obesity Research

Understanding WHY WE EAT and overeat

Obesity has become a global medical epidemic within the past 20 years, and it is now considered a greater threat to health and lifespan than is either undernutrition or infectious disease. In Canada, 59% of adults are overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2) 2 and the prevalence of overweight and obesity are rapidly increasing in Canadian children.

Chronic health risks of obesity include type 2 diabetes, hypertension, atherosclerosis, cardiovascular disease, certain forms of cancer and orthopaedic injury. In 1997, the estimated direct and indirect Canadian healthcare costs due to obesity were $2 billion! These costs are expected to rise as the today’s obese children get older. It is well kown that the increasing prevalence of obesity in both wealthy and impoverished nations is related to an increased visibility and availability of tasty but fat-laden foods as well as a decrease of physical activity.

However it is clear that the central nervous system (CNS) plays a significant role in the regulation of energy homeostasis. While making healthy changes to unhealthy lifestyles are clearly indicated for overweight and obese individuals, this approach may not be enough to help these individuals achieve a healthy weight: current data suggest that once an individual becomes obese, reversal of the condition is difficult in part because of “weight defending” changes in the brain.

This prospect is especially daunting to people who have become overweight early in life, and are faced with the possibility of a long future of ill health due to their inability to achieve a healthy weight. My research program aims to understand the physiology of neurons that regulate energy homeostasis. This is important because understanding the neuronal circuitry that regulates energy homeostasis is a step towards developing more effective strategies to prevent and treat obesity.

REGULATION OF ENERGY HOMEOSTASIS

SIGNALS FROM THE PERIPHERY

In mammals, the corticolimbic system is thought to mediate aspects of energy homeostasis such as procurement of food, sensory evaluation, social and hedonistic aspects of feeding. Additionally, the brainstem and hypothalamus are thought to play roles in aspects food intake such as detection of satiety signals, and the translation of information to control autonomic and neuroendocrine outputs. Satiety signals are circulating metabolites, hormones, adipokines and neuropeptides (such as glucose, leptin, ghrelin, insulin, amylin and glucagon-like-peptide) and are particularly important as they represent the primary means of communicating energy status from the periphery to the CNS.

SIGNALS FROM THE PERIPHERY

Recent work suggests that specific neurons of the arcuate nucleus of the hypothalamus (ARC) play a key role in detecting circulating satiety signals, however the role of these neurons is controversial because the ARC lies behind the blood brain barrier (BBB). Thus the ARC may be inaccessible to many satiety signals in the circulation that cannot pass the BBB. Therefore, a clear understanding of the mechanisms for detection of circulating satiety signals by the CNS is lacking.

SENSORY CVOS TRANSDUCERS OF SATIETY SIGNALS ACROSS THE BBB

The main focus of the research carried out in the lab is to understand the physiology of hunger and appetite by investigating the neurons that regulate homeostasis. In particular, the lab is interested in understanding regulation of electrical activity in neurons from circuits that control hunger, appetite, thirst and other aspects of energy homeostasis. Neurons from regions called the sensory circumventricular organs (CVOs) are thought to be especially important for regulation of homeostasis because these specialized areas are are not protected by the blood-brain barrier. The neurons within CVOs are in direct contact with hormones in the circulation and are able to sense hunger-stimulating and satiety (hunger-ending) hormones in the bloodstream: some of these hormones include ghrelin and leptin.