Barry E. Levin, M.D
Professor
 

Ambrose Dunn-Meynell, Ph.D.
Assistant Professor

Current Research Interests/Projects:
 

A strong case can be made that obesity is a disorder of neural function. The role of the brain in the regulation of body weight and energy homeostasis has become an increasingly important area. Numerous signals from the periphery inform the brain as to the energy status and adiposity of the body. The brain monitors glucose metabolism by sensing plasma glucose levels via specialized neurons in the brain and peripheral detectors which reach the brain via the vagus nerve. Neurohumoral signals are transmitted from the adrenal (corticosterone), pancreas (insulin) and adipose depots (the newly discovered adipose-specific protein, leptin) to the brain where they interact with specific brain receptors. Once the brain receives such signals, it can affect changes in peripheral metabolism using autonomic and neurohumoral outputs. We work in a rat model of diet-induced obesity in which rats all gain the same amount of weight when fed a low fat diet but show a marked bimodal weight gain pattern when fed a diet high in fat and energy content. Obesity-prone rats become obese only when exposed to such high energy diets while obesity-resistant rats gain no additional weight on such diets. Once the two weight gain phenotypes become well established, a new body weight setpoint is established and defended. This is associated with a corresponding permanent reorganization of their brains. Thus, this model represents a type of neural plasticity which continues similar lines of research done in this laboratory over many years. We have characterized the peripheral and central nervous system correlates of these weight gain phenotypes and have developed inbred colonies of rats which express the two weight gain phenotypes. This provides fertile ground for the investigation of the interaction of environment and genetic background, perinatal influences on brain development relative to obesity as well as specific investigations into the way in which the brain senses and regulates glucose.
 

Our laboratory takes a holistic approach to investigating the mechanism underlying the important interaction between genetic and environmental factors in this exciting animal model. Thus, we use a broad range of techniques which include: neurochemistry (HPLC, enzyme assays), molecular biology (in situ hybridization), receptor binding autoradiography, immunocytochemistry, microdialysis, electrophysiology (patch clamping), stereotaxic lesioning, in vitro monitoring of autonomic and metabolic status and behavior to characterize the many facets that underlie the propensity of a given animal to regulate their body weight and energy balance at these newly established levels. This work has direct application to the study and treatment human obesity and neurally-mediated disorders of energy balance.


Representative Publications

1. Levin, B.E., Brown, K.L. and Dunn-Meynell, A.A., "Differential effects of diet and obesity on high and low affinity sulfonylurea binding sites in the rat brain." Brain Res. 739: 293-300, 1996.
 

2. Dunn-Meynell, A.A., Routh, V.H., McArdle, J.J. and Levin, B.E., "Low affinity sulfonylurea binding sites reside on neuronal cell bodies in the brain." Brain Res. 745: 1-9, 1997.

3. Levin,B.E. and Routh,V.H. "Role of the brain in energy balance and obesity". Am. J. Physiol. 271: R491-R500, 1996
 

4. Levin,B.E. and Dunn-Meynell,A.A., "Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese rats." Am. J. Physiol. 272: R1365-R1370, 1997
 

5. Levin,B.E., Dunn-Meynell,A.A., Balkan,B. and Keesey,R.E., "Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats.", Am. J. Physiol. 273: R725-R730, 1997.
 

6. Levin,.B.E. and Dunn-Meynell,A.A., "In vivo and in vitro regulation of 3H glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucose." Brain Res.. 776: 146-153, 1997.
 

7. Levin,B.E. and Keesey,R.E., "Defense of differing body weight set-points in diet-induced obese and resistant rats.", Am. J. Physiol. 274: R415-R419, 1998.
 

8. Levin, B.E. and Govek, E., Gestational obesity accentuates obesity in obesity-prone progeny, Am. J. Physiol. 275: R1374-R1379, 1998.
 

9. Levin, B.E., Govek, E.K. and Dunn-Meynell, A.A., "Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rats", Brain Res., 808: 317-319, 1998.
 

10. Levin, Barry E., Arcuate NPY neurons and energy homeostasis in diet-induced obese and resistant rats, Am. J. Physiol. , 276: R382-R387, 1999.
 

11. Dunn-Meynell, A.A., Rawson, N.E. and Levin, B.E., "Distribution and phenotype of neurons containing the ATP-sensitive K+ channel", Brain Res., 814: 41-54, 1998.
 

12. Levin, B.E., Dunn-Meynell, A.A. and Routh, V.H., "Brain glucosensing and body energy homeostasis: role in obesity and diabetes", Am. J. Physiol. 276: R1223-R1231, 1999.