Physiology of Eating - L7

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 

- 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 

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

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 

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) 

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 

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) 

1. amygdala

2. NA

3. orbifrontal cortex

4. ventral pallidum

5. ventral tegmental area 

1. dopaminergic neurons are located in the substantia nigra (SNc) and the ventral tegmental area (VTA)

2. axons of dopaminergic neurons project to cortical areas (prefrontal cortex & limbic areas) 

3. these projections form mesocortical & mesolimbic dopamine pathways 

- matures at age 20

- involved in decision making, attention, working memory, behavioral flexibility (vulnerable to drugs, alcohol, stress, diet)

1. mesolimbic dopaminergic neurons in the VTA project to NAc and enhance reward value of palatable food 

2. LHA neurons integrate reward-related input from NAc with information related to energy homeostasis from ARC neurons