Obesity has reached epidemic proportions and its secondary health consequences are dependent on white adipose tissue (WAT) distribution with visceral fat increasing their incidence and severity. We study a naturally occurring photoperiodic obesity in Siberian hamsters because it shares the differential regulation of visceral vs subcutaneous WAT distribution with humans. This obesity is reversible by moving hamsters from long 'summer-like' to short 'winter-like' days (SDs) and is mediated by pineal melatonin (MEL). SDs trigger a greater increase in lipolysis by visceral vs subcutaneous WAT through the sympathetic nervous system (SNS) innervation of WAT. We continue and broaden our focus on this obesity to include other lipolytic stimuli and ask: How does the SNS control the differential mobilization of lipid from WAT? In Aim 1, we test for convergence of brain SNS outflow projections to different WAT pads, brown fat and adrenal medulla using multiple variants of a transneuronal viral tract tracer (pseudorabies virus [PRV]). We also test for co- localization of neurons activated by acute lipolytic stimuli (cold, glucoprivation) using c-fos, with PRV-labeled WAT SNS outflow neurons. We test for co-localization of neurotransmitter receptors involved in lipolysis, using in situ hybridization with PRV-labeled WAT SNS outflow neurons. We test for differences in SNS drive patterns across WAT pads by these acute lipolytic stimuli via norepinephrine turnover (NETO).
In Aim 2, we itest if implants of a MEL receptor antagonist at MELla receptor + PRV-labeled WAT SNS brain sites block iSD-induced lipolysis. We test if SNS WAT denervation blocks SD-induced increases in WAT lipolysis/lipid utilization gene expression. We test which fat cell adrenoceptor subtypes underlie SD-induced SNS lipolysis by in vitro glyerol release assays in isolated adipocytes.
In Aim 3, if WAT sensory denervation exaggerates acute- (cold, glucoprivation) and chronic (SDs)-induced WAT NETO. These studies will provide new linformation on the role of the WAT SNS innervation in lipid mobilization and obesity reversal. )ERFORMANCE SITE(S) (organization, city, state) Department of Biology, Kell Hall and Natural Science Annex, Georgia State University, Atlanta, GA 30303 KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Role on Project Bartness, Timothy Dept. Biology, Georgia State Univ. PI Song, C-.Kay Dept. Biology, Georgia State Univ. Research Scientist Disclosure Permission Statement. Applicable to SBIR/STTR Only. See instructions. [] Yes [] No PHS 398 (Rev. 05/01 ) Page 2 Number pages consecutively at the bottom throughout Form Page 2 the application. Do not use suffixes such as 2a, 2b. Principal Investigator/Program Director (Last, First, Middle): Bartness, Timothy Jon The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers 1 Face Page .................................................................................................................................................. Description,
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