Project Title

The effect of leptin on metabolic- and cardiovascular-related pre-sympathetic hypothalamic neurons in mice.

Authors' Affiliations

Kynlee Hillard, Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN Matthew Zahner, PhD, Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN David Kyle Mounger, Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN Brooke Tipton, Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN Grayson White, Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN

Location

White Top Mtn

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

122

Faculty Sponsor’s Department

Health Sciences

Name of Project's Faculty Sponsor

Dr. Matthew Zahner

Type

Poster: Competitive

Classification of First Author

Undergraduate Student

Project's Category

Cardiovascular System, Nervous System, Physiological Controls and Systems

Abstract Text

Obesity has risen 75% in the United States since 1980 and an estimated 80 million American adults are considered obese. Obesity activates the sympathetic nervous system and is associated with neurogenic hypertension. Leptin is an obesity-related neuropeptide released from fat cells which reduces appetite and increases metabolism. Leptin activates metabolic and cardiovascular responsive pre‑sympathetic neurons within the hypothalamus. Although leptin increases metabolism and curbs appetite, it also increases blood pressure. Considering that one main goal of obesity treatments is to diminish the cardiovascular-related co-morbidities this is an unacceptable side effect for potential treatments. Thus, a better understanding of the role hypothalamic sites involved in obesity-related hypertension is necessary for successful treatments. Our hypothesis is that leptin activates hypothalamic neurons that control metabolic (raphe pallidus) and cardiovascular activity (RVLM, rostroventrolateral medulla) within the brainstem. To test our hypothesis we created a line of transgenic mice using the cre-lox recombination system to express the reporter gene tdTomato under the control of the leptin (ObRb) receptor gene. First, we performed a behavioral study to verify the physiological effect and optimal dose of daily leptin treatment. To do this we implanted mini-osmotic pumps for continuous subcutaneous leptin (400 ng/hr) administration and measured food intake and body weight over 4 weeks. To determine if leptin activates pre‑sympathetic hypothalamic neurons we performed neuroanatomical tracer studies in these mice. At the end of the 4-week period, we injected fluorescent retrograde tracers into the raphe pallidus (green, metabolic center) and RVLM (magenta, cardiovascular). We then performed fluorescence immunohistochemical labelling to identify leptin-induced neuronal activation cFos a marker of neuronal activation of these neurons. Data from this behavioral, neurophysiological and neuroanatomical study will provide a better understanding of the role of the hypothalamus in controlling blood pressure and metabolism in obesity. Information from this study will provide groundwork for a better understanding of central autonomic mechanisms of cardiovascular risk as well as risk introduced by drugs intended to treat obesity.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

The effect of leptin on metabolic- and cardiovascular-related pre-sympathetic hypothalamic neurons in mice.

White Top Mtn

Obesity has risen 75% in the United States since 1980 and an estimated 80 million American adults are considered obese. Obesity activates the sympathetic nervous system and is associated with neurogenic hypertension. Leptin is an obesity-related neuropeptide released from fat cells which reduces appetite and increases metabolism. Leptin activates metabolic and cardiovascular responsive pre‑sympathetic neurons within the hypothalamus. Although leptin increases metabolism and curbs appetite, it also increases blood pressure. Considering that one main goal of obesity treatments is to diminish the cardiovascular-related co-morbidities this is an unacceptable side effect for potential treatments. Thus, a better understanding of the role hypothalamic sites involved in obesity-related hypertension is necessary for successful treatments. Our hypothesis is that leptin activates hypothalamic neurons that control metabolic (raphe pallidus) and cardiovascular activity (RVLM, rostroventrolateral medulla) within the brainstem. To test our hypothesis we created a line of transgenic mice using the cre-lox recombination system to express the reporter gene tdTomato under the control of the leptin (ObRb) receptor gene. First, we performed a behavioral study to verify the physiological effect and optimal dose of daily leptin treatment. To do this we implanted mini-osmotic pumps for continuous subcutaneous leptin (400 ng/hr) administration and measured food intake and body weight over 4 weeks. To determine if leptin activates pre‑sympathetic hypothalamic neurons we performed neuroanatomical tracer studies in these mice. At the end of the 4-week period, we injected fluorescent retrograde tracers into the raphe pallidus (green, metabolic center) and RVLM (magenta, cardiovascular). We then performed fluorescence immunohistochemical labelling to identify leptin-induced neuronal activation cFos a marker of neuronal activation of these neurons. Data from this behavioral, neurophysiological and neuroanatomical study will provide a better understanding of the role of the hypothalamus in controlling blood pressure and metabolism in obesity. Information from this study will provide groundwork for a better understanding of central autonomic mechanisms of cardiovascular risk as well as risk introduced by drugs intended to treat obesity.