Hormonal regulation of appetite and satiety (week 7)

Question 1

how does CNS influence energy balance and body weight

Answer 1

By:
- behaviour - feeding physical activity
-ANS activity - regulates energy expenditure
-neuroendocrine system - secretion of hormones

Question 2

orexigenic

Answer 2

increase food intake
decrease energy store
decrease energy expenditure

Question 3

anorexigenic

Answer 3

decreased food intake
increase energy store
increase energy expenditure

Question 4

hypothalamic regulation - appetite and satiey

Answer 4

feedback regulation:
-signals produced in response to body nutritional status
-signals detected by the hypothalamus
-act to modulate food intake and energy expenditure

Question 5

Body weight and food intake are also regulated by long-term processes e.g.,adiposity signals. What are these signals ?

Answer 5

Leptin
Insulin
Adiponectin
Ghrelin
Resistin

Question 6

what are some orexigenic peptide hormones

Answer 6

NPY
Galanin
MCH
Orexins
Agouti
Ghrelin
Endocannabinoids

Question 7

what are some anaorexigenic peptide hormones

Answer 7

Leptin
Insulin
a-MSH
Cart
GLP-1
TRH
CRH
PYY

Question 8

what is aMSH

Answer 8

a melanocyte stimulating hormone formed by sequential cleavages of the proopiomelanocortin (POMC) precursor polypeptide

Question 9

what is POMC

Answer 9

Pro-opiomelanocortin, a precursor protein processed to produce various peptide hormones. Produced in the pituitary gland.

Question 10

where are aMSH levels high

Answer 10

in the hypothalamus and this peptide inhibits food intake (anorexigenic)

Question 11

what are melanocortin receptor subtypes

Answer 11

MC-3 and MC-4, mainly expressed in the brain. Synthetic agonist and antagonists to these suppress and enhance food intake respectively

Question 12

what does deletion of MC-4 or MC-3 do

Answer 12

causes obesity in mice

Question 13

explain neuropeptide y (NPY)

Answer 13

a 36 aa peptide; one of the most abundant in the human brain

injection of NPY into hypothalamus potently stimulates food intake and reduces energy expenditure (orexigenic)

repeated administration can lead to obesity

mice lacking NPY receptor subtypes, Y1 or Y5 pre-disposed to obesity

Question 14

agouti-related protein (AgRP)

Answer 14

AgRP co-expresses with NPY in ARC neurons
AgRP and Agouti (Ay) are antagonists to MC3 and MC4 receptors
Intracerebroventricular (ICV) AgRP causes long lasting hyperphagia (Orexigenic)

Question 15

adiposity signals - leptin

Answer 15

member of the cytokine family, 146 aa long, made and secreted from adipocytes

circulates in proportion to fat mass

high levels of leptin receptors (Ob-Rb) expressed on ARC hypothalamic neurons

ICV leptin inhibits food intake and decreases body weight of rodents

neuron specific deletion of leptin receptor (Ob-Rb) results in obesity

Question 16

biological roles of leptin

Answer 16

bone formation
tumorigenesis
angiogenesis
maintenance of reproductive system
maintenance of immune system
peripheral glucose homeostasis/ insulin sensitivity

Question 17

adiposity signals- insulin

Answer 17

circulates in proportion to adiposity
transport system for insulin to enter brain
high levels of insulin receptors expressed in hypothalamus most notably in the ARC
ICV insulin inhibits food intake and decreases body weight of rodents

Question 18

cholecystokini

Answer 18

site of secretion- enteroendocrine cells of deodenum and jejumen
stimulus - released in proportion to lipids and proteins in meals
action - signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract - NTS)

Question 19

peptide yy (PPY 3-36)

Answer 19

site of secretion - endocrine mucosal L-cells and G-I tract
Stimulus - Levels increase rapidly post-prandially
action - Inhibits gastric motility, slows emptying reduces food intake (hypothalamus)

Question 20

glucagon-like peptide 1 (GLP-1)

Answer 20

site of secretion - Lcells of G-I tracts (product of pro-glucagon gene)
stimulus - levels increase in response to food ingestion
action - inhibits gastric emptying and reduces food intake (hypothalamus and NTS)

Question 21

Oxyntomodulin (OXM)

Answer 21

Site of secretion - Oxyntic and L-cells of small intestine (produce of pro-glucagon gene)
stimulus - released after a meal
action - acts to supress appetite - mechanism and site unclear

Question 22

Obestatin

Answer 22

site of secretion - cells lining the stomach/ small intestine (peptide from gene encoding ghrelin)
stimulus - release in response to ingestion
action - reduces food intake (may act to antagonise ghrelin)

Question 23

agouti and obesity

Answer 23

gene encodes a small protein - AGOUTI - natural antagonist of the melanocortin 1 (MC- 1) receptor in melanocytes - responsible for hair colour

mutation results in gene rearrangement causing ubiquitous ectopic expression

Ay mutation leads to obesity

Ay also anatogonist for hypothalamic MC-4 receptor - this is the cause of obesity in this mouse model

Question 24

what Is JAK2-STAT used in

Answer 24

transcriptional regulation eg. SOCS3 and POMC

Question 25

what is IRS-PI3K used for

Answer 25

transcriptional regulation and electrical activity of neurons

Question 26

what is diet induced obesity linked to

Answer 26

characterised by high leptin levels (correlates with high fat levels )

Question 27

DIO results in leptin resistance what are the two main theories

Answer 27

Defective leptin transport into brain
altered signal transduction following leptin binding to its receptor

Question 28

contributors to hypothalamic leptin resistance

Answer 28

hyperleptinemia - driven by high calorie intake - if decrease leptin, restore leptin sensitivity

ER stress - hypothalamus - decreases leptin sensitivity

inflammation - high calorie intake promotes chronic low-grade neuroinflammation including the hypothalamus

Question 29

what is the summary of this lecture

Answer 29

The hypothalamus plays a key role in regulating bodyweight and food intake
* Feedback loops act to modulate food intake and energy expenditure
* Adiposity signals are released from adipose tissue to regulate food intake
* Satiety signals are released from the GI tract to regulate food intake
* The brain becomes insensitive to leptin and insulin in obesity
* Rodent models of obesity e.g. Ob/Ob and db/db mice