Abstract
Otsuka Long-Evans Tokushima Fatty (OLETF) rats have a null mutation to the CCK-1 receptor and gradually develop obesity and type-2 diabetes. To date, the Roux-en-Y gastric bypass (GBP) surgery is the most successful intervention for weight loss. Based on observations in GBP patients suggesting altered food choices, and our previous findings showing that OLETF-GBP rats exhibit a reduced two bottle preference and a decreased lick-response to high concentrations of sucrose compared to sham-operated OLETF rats, in the present study we investigated the electrophysiological effects of GBP surgery on sucrose concentration coding in this strain. After GBP, obese OLETF rats lost and maintained body weight similar to that seen in human (−25 to 30%) and demonstrated improved glucose tolerance compared to pair-fed sham-operated OLETF rats. Extracellular single neuron recordings in the pontine parabrachial nucleus revealed that taste neurons of sham-operated OLETF rats with ad libitum access to food have an increased response function to higher concentrations of orally applied sucrose. This effect was reversed by GBP surgery. The relative distribution and response characteristics of neurons that best responded to sweet versus salty taste in OLETF-GBP but not in LETO-GBP rats were also altered by GBP. These findings demonstrate altered taste coding in this obese model and the capacity of GBP surgery to alleviate these impairments. A similar mechanism may be responsible for changes in eating habits and food choice reported in GBP human patients. Supported by NIH Grants DK065709, GM55639, PA-TS Fund, and PSU Diabetes Center Seed-Grant.
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