Food intake Flashcards
(26 cards)
Why is correct regulation of food intake important? (3)
-Energy (food) is essential to fuel our bodies
- Low energy availability causes changes in response to other stimuli
-Excess or insufficient energy can contribute to disease
–Obesity
–Anorexia-cachexia
What are the internal + external cues that may regulate energy homeostasis? (10)
internal:
-Food
-taste
-social habits
-environment
- Looking/foraging for food
external:
- hormones
-growth from the muscle
- signals from WAT/liver, pancreas (bidirectionally connected to the brain)
- gut-brain microbiome axis
-metabolism
-neuroendocrine communication
the brain exerts a top down influence on external + internal cue. What does this mean?
The brain is overseeing the integration of information from a variety of external = internal cues .
What are the 2 primary drivers of food intake? (2)
homeostatic vs hedonistic feeding
Define homeostasis
The tendency towards a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes
Define Hedonism
The pursuit of pleasure; sensual self-indulgence
What are the areas that communicate b/w brain areas that regulate feeding behaviour? (4)
-cortico-limbic system (reward, learning + memory, executive control) <— visual/olfactory/auditory stimuli + cues
-hypo (master nutrient sensor, incentive motivation)*
-hindbrain (oromotor + autonomic controls, satiation) *
= ingest -> taste -> gut -> absorbed + stored nutrients
** result in endocrine + autonomic outflow (most important)
Brain areas classification for regulating feeding behaviour (3)
autonomic:
-sensing of nutrional or energy reserve status (homeostatic signals)
- relaying homeostatic signals to the forebrain
-controlling adaptive thermogenesis
executive: (PFC + Nacc)
-decision to eat + to commit exercise
reward: (ventral tegmental area + limbic system (amygdala)
- establishing the hedonic + incentive or motivational salience properties of eating-related stimuli
Dorsal vagal complex info (5)
- Bi-directionally connected to peripheral organs via the vagus
- Direct nutrient and hormone sensing
- Contains neurons expressing a variety of neuropeptides
- Meal control and processing of sensory information
-Sends direct projections to the hypothalamus (PVN
The (important) hypothalamic nuclei (4)
- ARC
-VMN
-PVN
-SCN
CNS regulation of energy homeostasis balance (4)
balance b/w food intake + energy expenditure
- nutritional (e.g. glucose)
- humoral (e.g. leptin)
- nervous (e.g. vagal)
The central melanocortin system **
1) ME
2) ARC
3) PVN, LH, CEA, BST
4) LPB, RET
5) DMV
6)
Proopiomelanocortin (POMC) info (5)
- Neurons containing POMC found in the ARC (possibly NTS)
- Corticotropes of the pituitary also produced POMC
- Cleaved by prohormone convertases to a variety of peptide that have differential effects
- Cleavage products have different affinities for the different melanocortin receptor subtypes (1-5)
-Agonist activity of the MSH peptides on MC4R inhibits feeding
Loss of POMC function causes… (3)
- Obesity (lack of MC3R or MC4R agonism)
- Endocrine abnormalities (adrenal insufficiency; lack of MC2R agonism)
-Changes in pigmentation (lack of MC1R agonism)
How does Leptin directly regulate POMC neuron activity? (3)
- Fasting decreases hypothalamic POMC mRNA
–Can be reversed following leptin treatment
–Leptin-deficient ob/ob mice do not show fasting-induced regulation of POMC
-POMC neurons in the ARC and NTS are directly responsive to leptin
–Express leptin receptors
–Show pSTAT3 expression after leptin treatment
-Loss of leptin receptors on POMC neurons causes enhanced weight gain
Agouti-related protein (AgRP) info (4)
-Co-expressed with NPY in ARC neurons
- GABAergic
-Activity of AgRP neurons increases feeding
–AgRP = inverse agonist at MC4R
–NPY/AgRP neurons inhibit the activity of ARC POMC neurons
–Injection of AgRP in rodent brains stimulates feeding
-Ablation of NPY/AgRP neurons in adult animals leads to loss of drive to eat and starvation
-Optogenetic stimulation of AgRP neurons alters feeding (eg Mice without ChR2 expression in AGRP neurons (n= 11) did not show a significant difference in food intake during photostimulation, whereas in mice with greater than 800 ChR2-expressing neurons)
Effects of fasting(energy state + leptin) on NPY/AgRP neurons (3)
- Fasting increases NPY and AgRP gene expression
-Fasting increases activity (spike frequency of ARC NPY/AgRP neurons)
-Leptin treatment reverses the fasting-induced changes in NPY and AgRP gene expression and activity of these neurons
–Leptin receptors found on NPY/AgRP neurons
Ghrelin def (1)
A hormone produced from the stomach that stimulates appetite
Fasted animals are more sensitive to ghrelin
Npy/AgRP neurons + ghrelin (4)
- NPY/AgRP neurons are directly responsive to ghrelin
- Express ghrelin-receptors (GHSR)
- Ghrelin treatment increases ARC NPY/AgRP levels
- Ghrelin increases the firing rate of NPY/AgRP neurons (figure)
Melanocortin 4 receptor (MC4R) Info (5)
- GPCR with constitutive activity
- Evidence of coupling through multiple alpha subunits
- Agonists = POMC cleavage product (melanocyte stimulating hormones)
- Inverse agonist = AgRP
- Has GPCR independent coupling to an inward-rectifying potassium channel – Kir7.1.
Loss of MC4R signalling results in obesity (4)
CNS MC4R expression:
- Hypothalamus
- DVC
- Mesolimbic-dopamine system
- Loss of MC4R causes hyperphagia and obesity
- Animals gain even more weight on a high-fat diet
- Animals and people with altered MC4R signalling show increased preference for high-fat over high-sugar foods
MC4R in the PVN (2)
MC4R in the PVN are critical for regulating feeding Via AgRP neurons
Impact of MC4R on energy expenditure mediated by another brain region
Melanocortin 3 receptor (MC3R) (4)
- GPCR
- Expressed in the CNS (more limited expression than MC4R)
- Expressed on ARC POMC neurons (autoinhibitory)
- Loss of MC3R:
– Increases adiposity (baseline)
– Alters the response to deviations in energy availability (high or low)
Leptin deficient mice have broad neuroendocrine deficits - egs (8)
Hyperphagic
Glucose intolerant
Hypometabolic
Hypothermic
Low fertility
Reduced immune function/delayed wound healing
Defects in HPA axis
Reduced linear growth
