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Orexin and Thermogenesis
Yufeng Zhang
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Background Physiological Function Counter-productive nature
Non-shivering thermogenesis (BAT) Sleep/awake cycles Physicial activity Cognition Counter-productive nature Increase feeding Elevating energy expenditure Diet-induced thermogenesis Arousal from hibernation
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Background Autonomic function, both central and peripheral
Blood pressure, heart rate HPA axis, GNHR/soma-tostatin-GH axis Influences psychological, behavioral, and physiological characteristics Hibernation Thermogenesis (holding and raising) Arousal from hibernation
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Orexin and feeding Negative feedback system
Glucose Coordinate various elements of appetite regulation system Leptin, NPY, Galanin, Gherlin Interdependent functions between NPY and orexin
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Orexin and sleep/awake cycle
Orexin neurons project to Locus coeruleus (LC) Dorsal raphe (DR) Tuberomammilary nucleus (TMN) GABA → laterpdorsal tegmental nucleus (LDT)
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Orexin and BAT BAT Multiple lipid droplets, numerous mitochondria, dense capillary network UCP 1 Sympathetic nervous system → noradrenalin → β-3 adrenergic receptors → lipolysis Orexin-knockout mice, orexin receptor 1- deficient mice Hypersensitivity to cold Developmental differentiation defect
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Orexin and Hibernation
During hibernation, thermogensis depend on BAT Paradoxical actions: feeding and energy expenditure BAT in human BAT increase in size during hibernation
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Conclusion
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Stress-induced hyperthermia
Core body temperature rise under stress measure antistress or anxiolytic-like effects Orexin neurons with stress-induced thermogenesis Located in dorsol-medial hypothalamus (DMH) Project to medullary raphe ORX-KO and ORX-AB ORX-AB more REM than ORX-AB
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Conclusion/introduction
Orexins do not regulate resting body temperature. Orexin neurons in stress-induced thermogenesis Function as DMH-raphe neurons Receive stress then activate DMH-raphe neurons FGE2 injection and cold exposure Dynorphin, Galanin, Glutamate
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Conclusion Orexin neurons can be sources of glutamate transmission for cold-evoke thermogenesis Orexin may be involve with PGE2 shivering Orexin neuron participate in thermogenic output pathways Glutamate from orexin neuron could be responsible for thermogenic response
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