Physiology Flashcards
Cognitive control of eating
frontal lobe
cingulate cortex
inferior frontal cortex
Attention to external food cues
frontal
parietal
occipital
+visual areas
Amygdala
activates to food cues even when not hungry
Hippocampus
-responds to memory and experiences
-can override hunger and satiety based on food cues
Reward center sites receiving DA signals
-response to food cues (high cal, high fat)
Sup to inf:
1- dorsal striatum
2- nucleus acumbens
2- substantia nigra
4- VTA (ventral tegmental area)
Homeostatic control of eating
-1o site
-cues
-controls
-primarily in arcuate nucleus
-responds to peripheral signals: 1- gut hormones, 2- adipose hormones, 3- nutrients
-controls appetite & E exp
Orexigenic Pathway
= hunger
- Ghrelin +stim, Leptin/insulin inhibit
- 1st order neuron: AgRP/NPY in arcuate nucleus
- Receptors: Y1, Y5, (**AgRP also blocks MC4R) ?blocks a-MSH to MC3R & MC4R
- 2nd order neuron: __ in hypothalamus PVN
- Increase food intake
Anorexigenic pathway
= fullness
- Leptin & insulin +stim
- 1st order neuron: POMC/CART in arcuate nucleus
- Receptors: MC4R, MC3R
- 2nd order neuron: __ in hypothalamus in PVN
?aMSH - Reduced food intake & inc EE
PNS signals
-duration
-vagus roles
-short-acting
-vagus
afferent (sensory input): regulate motility, glucose production, gut hormone secretion
efferent (output): hormones CCK, PYY, GLP-1, insulin
E expenditure impacted by (5)
-ambient temp
-circadian rhythm
-nutrition
-inflammation
-reproductive state
Central regulation of E exp (3)
- SNS outflow -> NE -> thermogenesis by BAT
*SNS also influenced by glucose, ins, lep, GLP-1 - SCN produdes TGF-a –| locomotor via subparaventricular zone in hypothalamus
- Orexin-A produced in hypothalamus –> locomotion, wakefulness
Peripheral regulation of E exp (3)
- Insulin & leptin signal amount of fat stores
- Leptin –> locomotion to POMC neurons
- IL-6 from muscle during exercise –> mobilize fat to provide E to mm
Most variable component of TDEE
Activity-induced
Adipocyte signals
1. Diff’n: fibroblast –> pre-adip
2. Mat’n: maturation
3. inhibition of proliferation
- Diff’n:
PPAR-g stimulated by
-environmental factors
-obesogenic meds
-human ad-36 - Mat’n
insulin, GFs, glucocorticoids - SNS inhibits prolif
-Normal amount of visceral fat
-Least metabolically active
-10%
-lower body subQ
White vs Brown:
-shape
-mito
-other
White:
-spherical
-low mito
-TG droplets
Brown:
-polygonal
-high mito (color from iron)
-multiple lipid droplets
*critical for body temp
*adaptive thermogenesis in resp to food or cold (nonshivering via UCP1 in mito), burns fat and glucose
*more nerves than white, mediated by hypoth & SNS innervation (NE)
Beige adipose
?aka Brite
-chars of both white and brown, UCP-1 in mito
-PET+ areas (supraclav, suprarenal, pericard, paraAo, panc, kids, trach)
-within WAT
“Beiging” occurs due to (–> = theories)
diet –> high fat feeding ↑ UCP-1, ?polyuns ↑↑, high protein (esp. whey), capsaicin
exercise –> irisin from myokines ↑ UCP-1 in WAT
pre/post biotics
drugs
plant-based bioactives
adipokine
insulin/leptin –> POMC –> beign WAT
Anabolic & Catabolic Cycle
Anabolic (= Orexogenic, need nutrients to build):
↓ lep & insulin = E deficit
disinhibits (↑) NPY/AgRP, ↓ POMC/CART
↑ food intake, ↓ met rate
Food ↑ insulin & leptin = +E balance
↓ NPY/AgRP, ↑ POMC/CART
↓ food intake, ↑ met rate
Anabolic pathway vs. Catabolic pathway signaling in ARC
An = Orexigenic (NPY, AgRP)
Cat = Anorexigenic (POMC/CART)
Most metabolically active adipose tissue anatomically
SubQ abdominal (upper body)
-lower body least active
Visceral adipose hormones (5+)
adiponectin
leptin
TNF
resistin
IL-6
and more…
Pro-inflammatory adipokines
leptin
visfatin
apelin
chemerin
resistin
Anti-inflammatory adipokines
adiponectin
omentin
vaspin
Lipokines from adipose
palmitoleate
diHOME ?
FAHFA species
*regulate metabolism
↑ by diet, exercise, cold exp
RNA adipose-derived extracellular vesicles
-endocrine messengers: imm mod, ins sens, T cell diffn
-paracrine: ↑ lipogenesis
*modulated by hypoxia, sat fat, pro-infl cytokines
Leptin
-source
-receptor
-functions
** primarily WAT
** receptor in hypothalamus
** PRO-inflammatory
** Satiety (hypothalamus via NPY & POMC
** Regulates lipid homeostasis
** ↑ EE on CV system and thermogenesis via hypothalamus
-↑ SNS tone (directly and via aldo -> SNS -> ang II –| ins receptors)
-Modulates glucose homeostasis periph and centrally
-↑ ins sens
-inhibits hCG-med testost
-↑ ov steroids
(few other things on slide)
Adiponectin
-source
-receptor
-functions
** adipocytes & skeletal muscle
** receptor throughout body
** ANTI-inflammatory
** Ins sensitizing (↑ glu uptake, ↓ liver glucose output)
** CV: ↓ early athero and uangiopathy
- ↓ mm and liver TG deposits
(few other things on slide)
Ghrelin
-source
-receptors
-role
-produced by stomach (also epsilon cells of panc)
-receptors widespread but for eating primarily in hypothalamus
-Orexigenic (initiate eating, ↑ meal size)
–> adrenal cortisone; GH
–| GnRH, glucose-stim insulin secrn by panc, thyroid hormone effects
also sleep/wake rhythms, taste sensation, ↓ ins resistance
** only peripheral hormone related to hunger
GLP-1
-source
-receptors
-role
-L-cells in sb & colon in response to food intake
-receptors in hypothalamus & gut
-ANorexigenic, SHORT-acting
-↓ gastric emptyhing
↑↑ after bypass small bowel
Additional satiety hormones (7)
Intestine:
-CCK
-PYY
-OXM (oxyntomodulin)
-enterostatin
-GIP (gluc-dep ins-tropic polypep)
Panc:
-amylin
-insulin
Direct vs Indirect calorimetry
Driect:
-heat loss/production measured in enclosed chamber
-60% of food energy liberated as heat, 40% stored as ATP
Indirect:
-measuring heat production via CO2 cons & O2 prod
-desktop systems (doubly labelled water for research only)
Metabolism across lifespan
-highest
-adults
-
-infants highest per lb. (50% higher than adult)
… ↓ 3% per year until 20 yo, then levels off…
-adults STABLE even in preg and post-partum
-age 60 yo ↓ 0.7% per year
Carb metab
↑ insulin
immediate energy
or
stored as glycogen
or
liver full –> stored as fat
Protein metabolism
↑ insulin
if AA’s not needed –> goes to liver –> gluconeo
if liver full, stored as adipose
Fat metabolim
Emulsificaion
↑ insulin
Send throughout body OR stored in adipocytes
Sleep and Metabolism
-metab ↓ 15% during sleep
-lowest glucose metab in NREM & intermed REM
-GH highest in slow-wave sleep
-↑ cortisol secod half of sleep (primary REM)
↑↑ leptin
↓ grehlin during latter part of night
Circadian Alignment
-location
-influences
-hormones
-deprivation
*synchronization of 24 cycle needed to have stable sleep & EE
-master circ clock in SCN
-EE & food can influence clock in SCN
-hormones with circh rhythm: leptin, insulin, cortisol
-sleep deprivation ↑ Ghrelin
Orexin
-? link btw sleep & metab,
-nfluenced by leptin, ghrelin, glucose
… addendum slides not done, p 38-42 … adipokines, satiety & hunger hormones)
