Neuroendocrinology of Energy Homeostasis

Question 1

What are 3 sources of metabolic fuel in the body?

Answer 1

Carbohydrate
Fat
Protein

Question 2

What is energy balance achieved by?

Answer 2

Matching energy expenditure & food intake

Question 3

What happened when rats had a lesion of lateral hypothalamus?

Answer 3

Lost weight

Question 4

What happened when rats had a lesion of ventromedial hypothalamus?

Answer 4

Gained weight

Question 5

What two things do neural pathways link?

Answer 5

Hypothalamic nuclei with each other & other brain centres

Question 6

What are some hormones found in adipose tissue?

Answer 6

Leptin
IL-1
fatty acids
chemokines
adiponectin

Question 7

What is leptin?

Answer 7

167aa peptide hormone

Question 8

What is leptin secreted by?

Answer 8

Adipocytes

Question 9

What does leptin function as?

Answer 9

Indicator of adiposity (energy stores)

Question 10

How does leptin exerts its effect?

Answer 10

via a cell membrane receptor -> type 1 cytokine receptor family, JAK/STAT pathway

Question 11

What is the only active leptin receptor?

Answer 11

LepRB (CNS)

Question 12

What are some actions of leptin?

Answer 12

Food intake & energy expenditure matching
vascular function (atherosclerosis)
reproduction (placental function)
bone & cartilage (regulation of bone mass)
immune system modulation
also targets kidneys, bowel, pancreas, muscle

Question 13

What happens in the ob/ob mouse?

Answer 13

null mutation of leptin gene (chr6) -> obesity & mild diabetes

Question 14

What happened in the db/db mouse?

Answer 14

null mutation of leptin receptor gene -> obesity, fatal diabetes & hyperleptinemia

Question 15

What is the difference between the mice and satiety factor?

Answer 15

db/db = overproduced satiety factor but couldn’t respond to it
ob/ob = responded to satiety factor but could not produce its own

Question 16

Which stomach hormone is not a satiety factor?

Answer 16

Ghrelin

Question 17

What is ghrelin?

Answer 17

peptide hormone (28aa) produced in P and D1 cells in fundus

Question 18

What other cells is ghrelin found in?

Answer 18

Epsilon cells (islets of langerhans)
arcuate nucleus (hypothalmus)

Question 19

What does ghrelin have an effect on?

Answer 19

increases glucose, lipid and energy metabolism in liver, adipose tissue & pancreas

Question 20

What brain regions does ghrelin signal?

Answer 20

Hypothalamus
Hippocampus
ventral tegmentum & NA
brainstem

Question 21

What is ghrelin synthesized as?

Answer 21

94 aa prohormone

Question 22

What does processing yield?

Answer 22

Mature ghrelin & obestatin

Question 23

What does the active form of ghrelin have?

Answer 23

n-octanoic acid moiety -> essential for receptor binding & crossing BBB

Question 24

What does antagonism of ghrelin receptor reduce?

Answer 24

Food intake & body weight gain

Question 25

What are the names for the feeding and satiety pathways?

Answer 25

orexigenic = feeding anorexigenic = satiety

Question 26

What happens if the MC4R melanocortin receptor is defective?

Answer 26

cause autosomal dominant obesity

Question 27

What protein is a functional antagonist of the melanocortin 4 receptor?

Answer 27

Agouti related protein

Question 28

What does overexpression of Agrp in transgenic mice cause?

Answer 28

Hyperphagia & obesity mimicing effect of MC4R deficiency

Question 29

What brain regions do the feeding and satiety pathways signal to?

Answer 29

LHA DMN PVN VMN

Question 30

What two brain areas is the hypothalmus linked to?

Answer 30

Nucleus accumbens Ventral tegmental area

Question 31

What 3 things are the NA and VTA associated with?

Answer 31

Pleasure reward hedonic pathways

Question 32

What system is found throughout the CNS and PNS?

Answer 32

Endogenous lipophilic cmpounds -> Endocannabinoid system

Question 33

What processes are ECS implicated in?

Answer 33

Appetite regulation pain-sensation mood memory psychoactive effects of cannabis

Question 34

Which EC receptor is the most abundant?

Answer 34

CB1 found in the brain & nervous system highly expressed in NA

Question 35

What is CB1's endogenous ligand?

Answer 35

Anandamide & binds phytocannabinoid THC

Question 36

What do endocannabinoids act as?

Answer 36

Appetite signals

Question 37

What are exogenous cannabinoids?

Answer 37

Tetrahydrocannabinol 2 arachidonglycerol

Question 38

What is a selective receptor blocker of CB1?

Answer 38

Rimonabant -> reduce food intake

Question 39

What happens if FAAH is mutated?

Answer 39

Increased BMI as EC is not degraded