Transcript Orexin and Thermogenesis

Orexin and
Thermogenesis
Yufeng Zhang
Background
• Physiological Function
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Non-shivering thermogenesis (BAT)
Sleep/awake cycles
Physicial activity
Cognition
• Counter-productive nature
– Increase feeding
– Elevating energy expenditure
• Diet-induced thermogenesis
• Arousal from hibernation
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
Orexin and feeding
• Negative feedback system
– Glucose
• Coordinate various elements of appetite
regulation system
– Leptin, NPY, Galanin, Gherlin
• Interdependent functions between NPY and
orexin
Orexin and sleep/awake cycle
• Orexin neurons project to
– Locus coeruleus (LC)
– Dorsal raphe (DR)
– Tuberomammilary nucleus (TMN)
– GABA → laterpdorsal tegmental nucleus (LDT)
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 1deficient mice
– Hypersensitivity to cold
– Developmental differentiation
defect
Orexin and Hibernation
• During hibernation, thermogensis depend on
BAT
• Paradoxical actions: feeding and energy
expenditure
• BAT in human
• BAT increase in size during hibernation
Conclusion
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
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
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