Regulation of Food Intake

Question 1

Body weight “set point” in rats

Answer 1

• homeostatic regulation of energy intake
• Whether you over or underfeed them, their weight comes back down to or goes back up to regular weight when returned to regular diet
• ?humans

Question 2

Adaptations to the Environment

Answer 2

Genetics

Increased Energy Expenditure

• Resting energy expenditure
• Thermic effect of food
• Activity (exercise and/or nonexercise)

Reduced Intake/Appetite

• Changes in appetite modulators
• Cognitive and/or behavioral changes

Changes in Substrate Metabolism
-Increased fat oxidation, reduced nutrient assimilation

Question 3

Physiologic or homeostatic mechanisms of energy balance regulation

Answer 3

short term signals: meal related

long term signals: adiposity related

Question 4

Non-Homeostatic mech

Answer 4

• reward and motivation
• cognitive/executive decisions
• environmental cues
• social context

Question 5

hunger center

Answer 5

hypothalamus:

-Lateral Nucleus = “hunger center”
Lesion? aphagia (no eating)
-expresses melanin concentrating hormone (MCH) and orexins. Both induce feeding. Stimulate brainstem motor systems, cranial motor neurosn (trigeminal, facial, hypoglossal)

• Ventromedial nucleus= satiety center
• stimulation? cessation of eating.
• Lesion? eat excessively. (lesion has effect of ‘resetting’ regulated weight to higher level)
• arcuate nucleus:
• Paraventricular nucleus

Question 6

Leptin

Answer 6

Satiety hormone

Associated with stimulation of catabolic pathways and inhibit anabolic pathways to keep body in balance

-insulin is also considered a marker of adiposity and a homeostatic signal to brain (stop eating)

Leptin: stimulates POMC/CART and inhibits NPY/AgRP (activating satiety circuit and inhibiting feeding circuit)

Question 7

Neuropeptide Y

Answer 7

stimulates hunger and food intake

Question 8

MCR

Answer 8

catabolic pathway: reduce intake and increase energy expenditure

NPU stimulates anabolic and inhibits MCR (catabolic pathway)

Question 9

Ghrelin

Answer 9

from stomach, induces adiposity; stimulates appetite (anabolic pathways)

• receptors in arcuate nucleus (Ghrelin activates NPY and arcuate neurons)
• meal to meal (short term) regulation

Question 10

PYY, GLP-1

Answer 10

secreted by intestinal tract after meal

• Satiety type hormones (hunger level goes down)
• Stim POMC neurons and catabolic pathways (reduced food intake)

-Meal to meal regulation

Question 11

Hypothalamus

Answer 11

• direct pathways to reward pathways, limbic systems, cortex (prefrontal, motor, sensory)
• Pathways go in both directions

Question 12

People who might be prone to gaining weight could be resistant to…

Answer 12

leptin

Question 13

Obese people do NOT necessarily have MORE…

Answer 13

ghrelin

Question 14

“problems” with our biologic homeostatic regulation of food intake

Answer 14

Our biologic signals are primarily designed to protect us during times of undernutrition.
Perhaps it’s all about “resistance” to these signals, ie leptin resistance?

Question 15

Nonhomeostatic regulation of energy intake: internal inputs

Answer 15

Reward Mechanisms
Cravings
“Thinking” about food
Restraint
Learned Behaviors
Attention

Question 16

external inputs

Answer 16

Environmental Cues:
Sight
Smell
Taste
Availability/Portions
Social Context
Time cues

Question 17

When hungry, what is increased (fMRI)? Lean people

Answer 17

Brain areas imp in:
attention
reward
motivation
memory

Question 18

What about in people that are prone to obesity? What is increased (fMRI)?

Answer 18

Obese prone have PERSISTENT:
attention
reward 
motivation
memory

Question 19

Arcuate nucleus (hypothalamus)

Answer 19

• contains first order neurons that promote either food intake or satiety.
• Activation of arcuate neurons that produce both neuropeptide Y (NPY) and agouti-related peptide (AgRP) promote FEEDING
• Activation of arcuate neurons that produce both alpha-melanocyte stimulating hormone (alpha-MSH) and cocaine and amphetamine related transcript (CART) promote SATIETY
• alpha-MSH is a product of POMC precursor molecule

Question 20

arcuate nucleus neurons project to:

Answer 20

PVN: paraventricular nuclei and LH (lateral hypothal)

Question 21

alpha-MSH activates ___. What blocks effect of alpha MSH at this site?

Answer 21

Site: MCR (Melanocortin receptors)
Blocker? AgRP

Activation of Melanocorti receptors induces saitety

Question 22

NPY action

Answer 22

• increases hunger
• decreases energy expenditure (inhibits symp n.)

(NPY/AgRP neurons are thought to constitue a feeding system that is opposed by the alpha-MSH/CART satiety system)

Question 23

Gastric distension

Answer 23

-info carried by vagal afferents to nucleus of tractus solitarius (NTS), relayed to PVN/Arcuate nucleus/LH, amygdala, thalamus. From thal to visceral sensory cortex–> “gastric fullness”

Question 24

CCK

Answer 24

• duodenum signals brain about presence of nutrients thru release of CCK
• vagal afferents
• area postrema to send info to hypothal

Question 25

GLP-1

Answer 25

• released when food in ileum (from L cells)
• also on receptors in area postrema via NTS
• signals to reduce food intake

Question 26

Peptide YY (PYY)

Answer 26

• also from L cells like GLP-1

- anorexic effects by inhibiting hypothalamic NPY/AgRP neurons

Question 27

Glucose sensitive neurons location

Answer 27

VMN: stimulated by hyperglycemia
LH: inhibited by by glucose

Question 28

Area of brain involved in drug reward and food reward systems?

Answer 28

Nucleus accumbens and dopamine afferents.

Reciporocal connections between nucleus accumbens and LH

Question 29

POMC (alpha-MSH/CART) neurons are impacted by what NT?

Answer 29

serotonin

Also evidence that endogenous opioid system plays an important role in regulation of food intake, preference, choice (antagonists suppress intake)