Sleep and metabolism

• Relationship sleeping and eating?

  Bidirectional links sleep and metabolism to maintain homeostasis

  Energy conserved sleep (suspend activity, movement, sensory responses) - restore and replenish proteins

  Hunger during wake as many energy-demanding activities, promotes arousal and feeding, satiety following promotes sleep (changes neuroendocrine/neuropeptide signals)

  Signals interact/overlap with sleep/wake control - hypothalamus

  Other species spend less time sleeping to eat more (especially herbivores)

  Exception to mutual exclusivity is reindeer
• Sleep in anorexia?

  EEG shows changes in entire profile of sleep and SWA, profound depression of activity in patient
• List some of the metabolic functions of sleep?

  Glycogen store replacement, macromolecule biosynthesis, removal toxic metabolism products, recovery from oxidative stress, energy homeostasis, regulation glucose levels, thermoregulation, energy allocation
• Difference in sleep time based on diet and weight?

  Carnivores sleep more than omnivores, omnivores more than herbivores

  Sleep amount has negative correlation to body mass for all terrestrial mammals

  Therefore least sleep large herbivores, as low calorie diet means they need to almost constantly be eating
• Energy allocation model of sleep?

  Defines biological strategies that optimise temporal utilisation of energy, max reproductive success - based on single cell transcriptomics

  Wake - preferentially allocate energy to vigilance, foraging, reproduction - wake related transcripts for this (energy metabolism, excitatory neurotransmission, synaptic potentiation, memory acquisition etc)

  Sleep - allocate energy to growth, cellular repair, immune function, neural network reorganisation - sleep transcripts for protein synthesis, synaptic consolidation, membrane trafficking etc
• Role of relationship sleep and endothermy?

  Sleep achieves energy conservation in one way through reduction in body temperature in sleep, large effect metabolic rate and energy use

  Mice brains show state dependent fluctuations in temperature during sleep
• Effect of eating at different times of day?

  Feed mice with same high fat diet either light phase or dark phase, see much more weight gain in light phase mice - food not used as effectively

  Food powerful zeitgeber in absence of others - provide single meal at fixed time of day, see increase in food anticipatory activity several hours before feeding (increase by access to running wheel) - affects sleep/wake, as wake up when expecting food, can be awake during light phase - reorganisation sleep/wake cycle via homeostasis to adapt to feeding schedule
• What is torpor?

  Controlled lowering of metabolic rate and thus body temp, leads to inactivity - distinction from hypothermia (body cooling first)

  Molecular level = state where metabolism switches from consuming carbs to lipids (seen using respirometry ratio of oxygen and carbon dioxide)
• Examples of torpor?

  Mice show daily torpor as a response to poor environmental conditions - paradigm where more food if run more, see body temp reductions well below that of normal inactive circadian phase, energy saving, not seen when don't have to work for food

  Seen in variety of different animals, hibernation is form of torpor, but many others enter daily torpor

  See arousals during hibernation mammals, may be that sleep need accumulates in torpor, need periodic euthermy for sleep - sleep during arousals, but increased body temperature, reduces SWA power
• Is torpor sleep like or sleep depriving?

  Don't really know relationship of sleep and torpor, but animals emerge from torpor into intense sleep with lots of slow waves

  Don't know how torpor regulating neurons (found using DREADD/c-Fos studies, see neurons active when torpor induced, then activate to induce torpor) integrate information about internal and environmental experiences (mainly hypothalamic)

  Looks like sleep but not sleep - tightly linked regulation though
• How are sleep and energy homeostasis integrated?

  Hypothalamus key regulator available energy and sleep/wake control

  Leptin and grehlin signal to hypothalamus food intake/body weight - Leptin from adipose suppresses food intake, stimulates metabolic rate, grehlin from stomach and hypothalamus opposite

  Leptin deficient mice very obese, enter daily torpor, leptin may prevent?

  Hypocretin and MCH hypothalamus regulate energy-sleep balance, antagonistic - Hcrt neurons promote wake, feeding, inhibited by glucose and grehlin, excited by leptin (look at c-Fos expression), opposite MCH neurons
• Effect of glucose on VLPO and sleep switch?

  Glucose induces SWS by exciting sleep-promoting neurons in VLPO, reduced activity when low glucose - inject glucose into circuit mouse and falls asleep

  These neurons in VLPO are sleep active, so likely sleep promoting - mutual inhibition with wake promoting areas, when glucose there is inhibition of LH by VLPO and glucose itself so inhibit release of hypocretin, reduced activation wake promoting areas
• Effects of sleep loss on metabolism?

  Increased food intake and appetite (especially sweet food) - Reduced leptin, increased grehlin

  Activation SNS, increase corticosterone levels, alterations glucose utilisation, increase cardiovascular risk factors
• Relation sleep loss and obesity?

  Modern increase in both

  Glucose tolerance (and insulin) varies over 24hrs - plasma glucose responses to exogenous glucose higher evening than morning, minimum glucose tolerance middle of night

  6 day sleep restriction - increase glucose levels, reduced insulin sensitivity, reduced rate of glucose disposal and insulin secretion to intravenous GTT

  4hr sleep restriction 2 nights reduced leptin, increased grehlin and appetite, reduced motivation exercise, reduced NEAT

  VLPO lesion reduced sleep, no increase body weight - complex control
• Why does brain have high energy consumption?

  Due to cost of synaptic transmission - need to maintain ion gradients (~45% of the total ATP used), generate action and resting potentials, recycle transmitters etc - lots of energy needed to maintain neuronal excitability

  Highest glucose wake, lowest NREM - cerebral metabolism higher wake than sleep (use radioactive glucose), highest in the evening

  Brain uses 20% oxygen, 25% glucose body, only 2% of body mass
• Adenosine hypothesis of sleep?

  Adenosine release from ATP metabolism increases during wake, inhibits wake-promoting regions (BF, LH etc) - promotes sleep

  A1R agonists increase sleep propensity, delta waves

  A2A agonists increase sleep, c-Fos immunoreactivity VLPO

  Adenosine perfusion BF and LDT/PPT reduce wake, increase sleep

  Adenosine agonists inhibit mesopontine tegmentum cholinergic neurons, reduces Glu EPSCs and GABA IPSCs

  Increased adenosine release synchronises EEG, resynthesis glycogen

  Caffeine blocks A1Rs, reduces SWS, A1Rs SCN may mediate effect caffeine on circadian rhythms