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Physiology of Disease > Neuroendocrinology of Energy Homeostasis > Flashcards

Neuroendocrinology of Energy Homeostasis Flashcards

1
Q

What are 3 sources of metabolic fuel in the body?

A

Carbohydrate
Fat
Protein

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2
Q

What is energy balance achieved by?

A

Matching energy expenditure & food intake

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3
Q

What happened when rats had a lesion of lateral hypothalamus?

A

Lost weight

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4
Q

What happened when rats had a lesion of ventromedial hypothalamus?

A

Gained weight

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5
Q

What two things do neural pathways link?

A

Hypothalamic nuclei with each other & other brain centres

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6
Q

What are some hormones found in adipose tissue?

A

Leptin
IL-1
fatty acids
chemokines
adiponectin

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7
Q

What is leptin?

A

167aa peptide hormone

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8
Q

What is leptin secreted by?

A

Adipocytes

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9
Q

What does leptin function as?

A

Indicator of adiposity (energy stores)

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10
Q

How does leptin exerts its effect?

A

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

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11
Q

What is the only active leptin receptor?

A

LepRB (CNS)

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12
Q

What are some actions of leptin?

A

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

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13
Q

What happens in the ob/ob mouse?

A

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

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14
Q

What happened in the db/db mouse?

A

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

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15
Q

What is the difference between the mice and satiety factor?

A

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

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16
Q

Which stomach hormone is not a satiety factor?

A

Ghrelin

17
Q

What is ghrelin?

A

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

18
Q

What other cells is ghrelin found in?

A

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

19
Q

What does ghrelin have an effect on?

A

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

20
Q

What brain regions does ghrelin signal?

A

Hypothalamus
Hippocampus
ventral tegmentum & NA
brainstem

21
Q

What is ghrelin synthesized as?

A

94 aa prohormone

22
Q

What does processing yield?

A

Mature ghrelin & obestatin

23
Q

What does the active form of ghrelin have?

A

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

24
Q

What does antagonism of ghrelin receptor reduce?

A

Food intake & body weight gain

25
Q

What are the names for the feeding and satiety pathways?

A

orexigenic = feeding
anorexigenic = satiety

26
Q

What happens if the MC4R melanocortin receptor is defective?

A

cause autosomal dominant obesity

27
Q

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

A

Agouti related protein

28
Q

What does overexpression of Agrp in transgenic mice cause?

A

Hyperphagia & obesity mimicing effect of MC4R deficiency

29
Q

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

A

LHA
DMN
PVN
VMN

30
Q

What two brain areas is the hypothalmus linked to?

A

Nucleus accumbens
Ventral tegmental area

31
Q

What 3 things are the NA and VTA associated with?

A

Pleasure
reward
hedonic pathways

32
Q

What system is found throughout the CNS and PNS?

A

Endogenous lipophilic cmpounds -> Endocannabinoid system

33
Q

What processes are ECS implicated in?

A

Appetite regulation
pain-sensation
mood
memory
psychoactive effects of cannabis

34
Q

Which EC receptor is the most abundant?

A

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

35
Q

What is CB1’s endogenous ligand?

A

Anandamide & binds phytocannabinoid THC

36
Q

What do endocannabinoids act as?

A

Appetite signals

37
Q

What are exogenous cannabinoids?

A

Tetrahydrocannabinol
2 arachidonglycerol

38
Q

What is a selective receptor blocker of CB1?

A

Rimonabant -> reduce food intake

39
Q

What happens if FAAH is mutated?

A

Increased BMI as EC is not degraded

Physiology of Disease (15 decks)

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