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Fenster schliessen

3 parts of the brain important in eating control (6)

1. hypothalamus -> eating + regulation of energy (meal initiation)

- PVN, LH, ARC

2. caudal brainstem -> meal-related signals (meal termination)

- NTS, AP

3. forebrain -> memories + external modalities (reward & hedonic control of eating)

- PVN, LH, VTA, Amygdala, Hippocampus 

Fenster schliessen

Hypothalamus integrates 3 types of signals to initiate meals 

1. interoceptive humoral signals -> related to energy homeostasis

2. meal-related signals from GI tract -> via vagus nerve, spinal cord + ascending connections from hindbrain

3. information related to memores & external modalities -> via descencing connections from the forebrain 

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Hypothalamic Agrp/NPY neurons 

(5)

- located in ARC, regulated by circulating hormones

- stimulate eating + decrease energy expenditure

- activated by ghrelin, + low levels of insulin/leptin

- 1 effect: blocking of PomC/Cart & MC4 -> increased food intake

- 2 effect: direct effect on lateral hypothalamic area 

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Agouti Peptide (2) + agouti-related peptide (agrp) (5)

 

1.   = inverse agonist to peripheral MC1 receptors 

2. -> paracrine signaling molecule that causes hair follicle melanocytes to synthesize pheomelanin, a yellow pigment 

(mice expressing agouti peptide gene -> yellow pigment)

 

1. MC3/MC4 receptor inverse agonist

2. similar to agouti + has peripheral effects on hair or adipocytes 

3. brain: only expressed in hypothalamic ArC neurons 

4. inverse agonist on alpha-melanocyte-stimulating hormone in PVN

5. has effects on LH

 

Fenster schliessen

Reward-related input for the hypothalamus: 

(3)

 

1. Lateral hypothalamic area neurons integrate reward-related input from Nac with information related to energy homeostasis from ARC 

2. Fasting & low insulin/leptin levles & high ghrelin levels -> increase rewarding properties of food and have direct effects on the ventral striatum and indirect effects in LHA

3. LHA is in a KEY position & connects to other areas 

Fenster schliessen

Lateral hypothalamic ares: 

integrates.. (3)

Function (4)

1. humoral + nerval interoceptive information (energy homeostasis)

2. information related to memories + external modalities 

3. information related to circadian rhythm 

 

1. primary anabolic function: expresses ORX A, B and MCH 

-> MHC: stimulate eating via forebrain projections

-> ORX A, B: stimulate eating via projection to all parts of cerebrospinal axis

-> ORX neurons can also be activated by hypoglycemia (linking metabolism & alertness) 

Fenster schliessen

MC4R (4)

1. polymorphisms: most frequent monogenetic factor that influences BW in humans

2. inactivation -> dramatic weight gain in mice

3. human loss or gain-of-function MC4R variants shape body weight

-> gain of functions: decreased BW

-> loss of functions: increased BW 

4. influences meal size -> inactivation: no satation 

Fenster schliessen

Caudal brainstem (NTS, AP)

Integration of adiposity & satiation signals (4)

1. Leptin acts on AgrP & PomC (hypothalamus) + on hindbrain areas (NTS - caudal brainstem) 

2. Satiation signals activate vagal afferents that terminate in the NTS -> this is influenced by descending projections from PVN & ARC (e.g. oxytoci, aMSH) 

-> leptin enables satiation signals to act properly (lack of leptin diminishes responsiveness to satiation signals)