Lecture 32 - Feeding & Weight Control Flashcards
1
Q
Outline the metabolic syndrome
A
Obesity →
- Hypertension
- Dyslipidaemia
- Insulin resistance
2
Q
Outline the two types of peripheral signals involved in homeostasis of body weight
A
-
Satiety signals
- CCK, Ghrelin
- Short acting
- Produced in the gut, stomach & liver
- Action:
- Acts on Vagus & sympathetic nerves
- Transmission to medulla
- Further transmission to hypothalamus
-
Adiposity signals
- Leptin, insulin
- Long term
- Released from pancreas / leptin
- Circulate in levels proportional to fat mass
- Inform the hypothalamus about peripheral energy stores
- Action
- Released into blood stream
- Actively transported across the BBB
- Acts on neurons in the ARC
3
Q
State the overall action of the following peptides:
- Cholecystokinin
- Agouti-related peptide
- Ghrelin
- α-melanocyte stimulating hormone
- Leptin
- Neuropeptide Y
What is the source of these?
A
Appetite stimulating:
- Neuropeptide Y
- Agouti-related peptide
- Ghrelin
Appetite suppressing:
- α-melanocyte stimulating hormone
- Leptin
- Cholecystokinin
Source:
- Brain:
- NPY
- α-MSH
- ARP
- Periphery:
- Ghrelin
- Leptin
- Cholecytokinin
4
Q
Describe cholecystokinin (CCK)
- Source
- Action
- Release
A
- 33 AA
- Source:
- Cells in the intestine
- Release:
- In response to nutrients esp. fat in the lumen of the gut
- Action
- Overall: Satiety (decreased food intake)
- Acts locally on CCKA receptors on vagus nerves
- Signal transmitted to Nucleus tractus solitarius in medulla
- Ascending transmission to medulla
- Termination of meal
- Doesn’t have an overall effect on body weight
- Increased frequency of meals to compensate
5
Q
Describe Ghrelin
- Source
- Release
- Action
A
- 28 AA peptide
- Source
- Predominantly synthesised in the stomach
- Release
- Pre-prandially, when the stomach is empty
- Decreases post-prandially
- Action
- Overall: increase appetite & body weight
- Acts on GHSR-1a receptors in hypothalamus
6
Q
Describe Leptin
- Source
- Release
- Action
A
- Source:
- Predominantly adipocytes
- Release
- Post-prandially
- Action
- Crosses BBB
- Acts on receptors in the hypothalamus (ARC)
- Inhibits food intake
7
Q
Compare circulating levels of Ghrelin and Leptin
A
Ghrelin: inversely proportional to BMI & weight
Leptin: proportional to BMI & weight
8
Q
What is the role of Leptin in obesity?
A
- Initially thought that Leptin defects could play a role in the pathogenesis of obesity
- This is only the case for a low number of individuals
9
Q
Compare the sources of Leptin & Ghrelin
A
Leptin: adipocytes
Ghrelin: stomach
10
Q
Describe how Leptin regulates energy balance
A
- Leptin released from white adipose cells
- Leptin crosses BBB and binds to Leptin receptors on the hypothalamus
- Stimulation of POMC/CART neurons
- Inhibition of: **NPY/AGRP **neurons
- Release of neuropeptides:
- Control of food intake & energy usage
11
Q
Describe NPY
- Source
- Release
- Action
A
- 36 AA peptide
- Source:
- NPY/AGRP neurons in hypothalamus
- Release:
- Regulated by Leptin:
- Leptin signalling inhibits release
- Ghrelin stimulates release
- Regulated by Leptin:
- Action
- Binds Y1, Y2 & Y5 receptors
- GPCRs
- Y1/2
- Located post-synaptically
- Y5
- Located pre-synaptically
- Auto-receptors
- Stimulates feeding behaviour
- Reduces energy expenditure
- Binds Y1, Y2 & Y5 receptors
12
Q
Describe POMC
- Receptors
- Release
- Action
A
- Pro-opiomelanocortin
- 131 AA precursor protein
- Cleaved into a-MSH (amongst other peptides)
- Action
- Binds receptors in PVN
- MC(1-5) R
- Binds receptors in PVN
13
Q
Describe α-MSH
- Source
- Release
- Action
A
- 13 AA peptide
- Source
- Release:
- Regulated by leptin
- Leptin stimulates release
- Released into PVN
- Regulated by leptin
- Action:
- Tonically released:
- Acts on **MC4R **
- Inhibits food intake
- Increases energy expenditure
- Acts on **MC4R **
- → tonic inhibition of food intake
- Tonically released:
14
Q
Describe AGRP
- Source
- Release
- Action
A
- Agouti-related peptide
- 132 AA protein
- Source
- ARC neurons
- Release
- Regulated by leptin
- Leptin signalling inhibits release
- Ghrelin stimulates release
- Regulated by leptin
- Action
- Antagonist at MC4R
- Inhibits action of α-MSH
- Increases food intake
- Decreases energy expenditure
- Antagonist at MC4R
15
Q
What is ARC?
A
- Arcuate nucleus
- Located in the hypothalamus
- Contains NPY/AGRP & POMC/CART neurons