Appetite & Energy Balance - Adipose and Obesity

Question 1

Peripheral energy status is signalled to the brain by the fat-derived hormone _____ and somewhat by the pancreatic hormone ____

Answer 1

•Peripheral energy status is signalled to the brain by the fat-derived hormone leptin and somewhat by the pancreatic hormone insulin

Question 2

what gut derived factors influence appetite behaviour (4)

Answer 2

•The gut derived factors ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) influence appetite behaviour

Question 3

can the brain metabolize fatty acids

Answer 3

• The brain cannot metabolize fatty acids; receptors detect only glucose levels but the liver can metabolize both
• The liver and GI have good vagal connection to the brain

Question 4

Leptin

• secreted by:
• what does it do

Answer 4

•A cytokine like hormone secreted by adipose tissue; decreases food intake and increases metabolic rate, primarily by inhibiting neuropeptide Y (NPY)-secreting neurons in the arcuate nucleus of the hypothalamus

Question 5

what type of foods lead to a rapid increase in blood glucose

Answer 5

•High GI foods (things that are highly processed) stimulate a rapid increase in blood glucose

Question 6

Visceral adipose cells produce significant amounts of _______ cytokines which disrupt what?

Answer 6

• Visceral adipose cells produce significant amounts of proinflammatory cytokines
• These proinflammatory cytokines disrupt normal insulin action in fat and muscle cells and may be a major factor in causing the whole body insulin resistance observed in patients with visceral adiposity

Question 7

Orexigenic neurotransmitters (2) what are they and what do they do, what are they activated by

Answer 7

NPY and AgRP – which activate appetite (increase food intake) and are activated by ghrelin
-NPY = neuropeptide Y, -AgRP=Agouti-related peptide

Question 8

Anorexigenic neurotransmitters what are they and what do they do, what are they activated by

Answer 8

Anorexigenic neurotransmitters: POMC and CART – which inhibit appetite (decrease food intake) and are activated by CCK, PYY and GLP-1 and leptin

• POMC = Pro-opiomelanocortin
• CART = cocaine- and amphetamine-regulated transcript

Question 9

Endocrine appetite regulation*

1. fasted state has positive effects on which neurons
2. what do you produce more of when exposed to synthetic light
3. leptin positive vs negative effects
4. parasympathetic response

Answer 9

• in fasted state and produce ghrelin which will have + effects on orexigenic neurons which will have + effects on neurons producing orexins and MCH which stimulates us to eat when we are in the fasted state
• exposure to synthetic light at night you will start to produce more grehlin
• leptin and insulin from beta cells released from adipose tissue - insulin changes amount of glucose being taken up from adipose - it has negative effects on orexogenic centers just like grehlin will have negative effects on NTS to downregulate positive signals being released from lower levels of GI and vagus
• leptin positive effects on anorexogenic parts of brain and POMC neurons positive effects on PVN then after you’ve eaten it will start to stimulate u to use that and go out and exercise by increasing about of TRH, oxytocin and CRH
• parasympathetic response is digestion of all the food and go out and use because you have all that potential energy stored

Question 10

Neuropeptide - Y

NPY (3)

Answer 10

• most powerful appetite enhancer
• co-expressed with AgRP
• both released by negative energy balance (low leptin and hypoglycemia)

Question 11

AgRP - Agouti-related peptide

Answer 11

•high levels in obesity

Question 12

Proopiomelanocortin (POMC) - 3

Answer 12

• melanocortins (produces of POMC-aMSH) decrease food intake

* mutations in R (MCR4) = obesity, hyperphagia and hyperinsulinemia

Question 13

cocaine- and amphetamine-regulated transcript (CART) -2

Answer 13

• co-localized with POMC neurons

* role in decreased food intake complex

Question 14

Cholecystokinin (CCK) -3

Answer 14

• release from gut when nutrients in lumen
• CCK-1R on vagus never – indicates sense of fullness
• Infusion of CCK3 – decrease meal size and postprandial hunger

Question 15

Peptide YY (PYY) -4

Answer 15

• Released from L-cells
• Correlates with ingested calories
• Infusion = decreased food intake and increased intervals between meals
• Deficiency seen in obesity

Question 16

Glucagon-like-peptide 1 (GLP-1) - 2

Answer 16

• Infusion (rats) decreased food intake and body weight

* Agonist exendin 4 (Exenatide) = 21% decrease daily food intake

Question 17

Leptin - the obese gene (Ob or Rb)

1. where is it produced
2. circulating levels coorespond to what
3. inhibits what

Answer 17

• Produced in adipose tissue – indicator of body fat levels
• Circulating levels correspond to body fat
• Inhibits food intake, decreases appetite – inhibits NPY an AgRP neurons and stimulates POMC and CART neurons

Question 18

Leptin receptor belongs to which family and signals through what

• how many subtypes
• found where

Answer 18

•Leptin receptor – belongs to the cytokine R family, signals through STAT3

• 6 subtypes but only one (LepRb) with c-terminal tail for signalling
• found in the hypothalamus – ARC

Question 19

Grehlin - the hunger hormone

1. produced where
2. circulating levels
3. stimulates what

Answer 19

• produced in oxyntic glands of stomach
• circulating levels increase before and decrease after a meal
• stimulates appetite (short-term) – stimulates NPY and AgRP neurons and inhibition of POMC neurons
• stimulates the release of GH & other possible roles include the control of ACTH and prolactin glucose and lipid metabolism, gastric mobility and acid secretion, heart function, sleep, reproduction and antiproliferative effects

Question 20

Grehlin receptor is what and where is it found

Answer 20

•receptor is growth hormone secetagogue receptor (GHSR1a) – found in hypothalamus and pituitary – NPY and GHRH neurons

Question 21

*leptin in addition to appetite regulation (4)

Answer 21

• decreases intracellular lipid in muscle and liver
• decreases insulin sensitivity, decreases insulin secretion – insulin leptin regulates each other
• regulation of bone reabsorption
• low levels inhibit reproduction, thyroid thermogenesis and immune response

Question 22

Adiponectin (4)

Answer 22

Increase insulin sensitivity: increase fa oxidation increase glucose uptake and decrease gluconeogen

• Anti-inflammatory (decrease TNF alpha), anti-atherogenic
• Predominant targets: liver and muscle (Rs here and elsewhere)
• Concentration low in obesity, inverse correlation to BMI

Question 23

Adipocytokines (Tumor necrosis factor alpha (TNFa) and interleukin (IL-6))
(3)

Answer 23

• Pro-inflammatory: association with insulin resistance
• Levels increase with obesity
• Decrease your sensitivity to both leptin and insulin

Question 24

Resistin (2)

Answer 24

• Decreases insulin sensitivity

- Human adipose doesn’t produce it but mice do

Question 25

Estradiol (with high expression of aromatase) (1)

Answer 25

Fat produces estradiol which can become important when you have fat stores in breast (can become proliferative and increase risk of breast cancer)

Question 26

The more TNF alpha being released more IL-6 more _____ and _____

Answer 26

The more TNF alpha being released more IL-6 more visfatin and apelin

Question 27

Factors affecting weight gain

Beahvioural: 3 points

Answer 27

1)Behaviour – affected by environment, cultural attitudes and financial situation
•Diet – overeating
•Physical activity – sedentary lifestyle
•Lack of sleep – increases ghrelin and decreases leptin which increases appetite – half of Canadians are not getting enough sleep which can lead to hypertension, weight gain, depression and poor immune systems also increase work place accidents

Question 28

Factors affecting weight gain

Genetics:

Answer 28

influence how the body burns calories for energy and how the body stores fat – think about the history of our species

Question 29

Factors affecting weight gain

Age: 2 points

Answer 29

1)Age – obesity increases with age – physical activity goes down with age
•GH promotes lean (fat free) muscle which decreases with age so harder to keep weight constant
•E2 decreases with age, deficiency promotes feeding and weight gain