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 colocalization 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 test if implants of a MEL receptor antagonist at MEL1a receptor + PRV-labeled WAT SNS brain sites block SD-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, we test if WAT sensory denervation exaggerates acute- (cold, glucoprivation) and chronic (SDs)-induced WAT NETO. These studies will provide new information on the role of the WAT SNS innervation in lipid mobilization and obesity reversal.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Special Emphasis Panel (ZRG1-IFCN-D (05))
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Yanovski, Susan Z
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Georgia State University
Schools of Arts and Sciences
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Ryu, Vitaly; Zarebidaki, Eleen; Albers, H Elliott et al. (2018) Short photoperiod reverses obesity in Siberian hamsters via sympathetically induced lipolysis and Browning in adipose tissue. Physiol Behav 190:11-20
Thomas, M Alex; Xue, Bingzhong (2018) Mechanisms for AgRP neuron-mediated regulation of appetitive behaviors in rodents. Physiol Behav 190:34-42
Thomas, M Alex; Tran, Vy; Ryu, Vitaly et al. (2018) AgRP knockdown blocks long-term appetitive, but not consummatory, feeding behaviors in Siberian hamsters. Physiol Behav 190:61-70
Nguyen, Ngoc Ly T; Xue, Bingzhong; Bartness, Timothy J (2018) Sensory denervation of inguinal white fat modifies sympathetic outflow to white and brown fat in Siberian hamsters. Physiol Behav 190:28-33
Nguyen, Ngoc Ly T; Barr, Candace L; Ryu, Vitaly et al. (2017) Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment. Am J Physiol Regul Integr Comp Physiol 312:R132-R145
Ryu, Vitaly; Watts, Alan G; Xue, Bingzhong et al. (2017) Bidirectional crosstalk between the sensory and sympathetic motor systems innervating brown and white adipose tissue in male Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 312:R324-R337
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Evans, Jennifer A; Suen, Ting-Chung; Callif, Ben L et al. (2015) Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body. BMC Biol 13:43
Ryu, Vitaly; Garretson, John T; Liu, Yang et al. (2015) Brown adipose tissue has sympathetic-sensory feedback circuits. J Neurosci 35:2181-90

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