physiology - feeding and satiety

Question 1

energy homeostasis

Answer 1

physiological process whereby energy intake is matched to energy expenditure over time
>promotes body fuel stability - energy is primarily stored as fat

Question 2

how does obesity occur

Answer 2

accessible, calorie dense food plus sedentary lifestyle

ie small constant mismatch between energy intake and energy expenditure

Question 3

what are the causes and consequences of metabolic stress

Answer 3

we have abundant energy supplies + little energy demand >> leading to obesity 
>>metabolic syndrome 
>>dyslipidemia 
>>insulin resistance
>>type II diabetes 
>>CVD

Question 4

normal and abnormal BMIs

Answer 4

25 = thin or normal acceptable 
25-29.9 = overweight 
30-40 = obese 
>40 = morbidly obese

Question 5

how to calculate BMI

Answer 5

weight over square height

Question 6

factors contributing to obesity

Answer 6

obesity is a heterogeneous group of conditions with multiple causes
>genetics: through susceptibility genes, these increase risk of developing disease
>environment: ‘westernisation’ of diet

Question 7

SARS-CoV-2 metabolic disease connection

Answer 7

> obesity linked to most of the high risk factors for covid-19
western diet leads to activation of the innate immune system and inhibition of the adaptive immune system
adipose tissue contains the components for SARS-CoV2 entry and exit

Question 8

what does obese AT act as ? 2

Answer 8

an immune reservoir and a reservoir for the SARS virus
>higher viral load for longer
>poor recovery from disease
>prolonged viral shed from obese individuals
>efficacy of antivirals;s and vaccines reduced

Question 9

consequences of obesity

Answer 9

• stroke
• resp. disease
• heart disease
• gallbladder disease
• osteoarthritis
• dementia
• covid 19
• NAFLD
• diabetes
• cancer

Question 10

why do we need fat?

Answer 10

energy storage
prevention of starvation
energy buffer during prolonged illness
>starvation and infection has been a threat to human survival
>Adipose tissue accumulation would represent a survival adaptation

Question 11

why is it difficult to lose weight once gained ?

Answer 11

it is a disease of the brain ..
increased body fat alters brain function as long term obesity induces brain re-programming
ie your brain view the extra weight as normal and dieting as a threat to body survival

Question 12

what ways does the CNS influence energy balance and body weight ?

Answer 12

through

• behaviour (feeding and physical activity)
• ANS activity (regulates energy expenditure)
• neuroendocrine system (secretion of hormones0

**integration of these determines final output ie feeding behaviour

Question 13

where does this integration happen?

Answer 13

the brain !

the neural centre responsible is the hypothalamus

Question 14

what three basic concept underly the control system of energy intake and body weight

Answer 14

• satiety signalling
• adiposity negative feedback signalling
• food reward

Question 15

satiation

Answer 15

sensation of fullness generated during a meal

>satiation signals increase during meal to limit meal size

Question 16

satiety

Answer 16

period of time between termination of one meal and the initiation of the next

Question 17

adiposity

Answer 17

the state of being obese

Question 18

satiation signals - what are they

5 of them

Answer 18

>CCK - cholecystokinin 
>PYY3-36 - peptide YY
>GLP-1 - glucagon like peptide
>OXM - oxyntomodulin 
>obestatin

Question 19

CCK

Answer 19

secreted from enteroendocrine cells in duodenum and jejunum
>released in proportion to lipids and proteins in meals
>signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract - NTS)

Question 20

Peptide YY

Answer 20

secreted from endocrine mucosal L cells of GI tract
>levels increase rapidly post-prandially
>inhibits gastric motility, slows emptying and reduces food intake

Question 21

glucagon like peptide

Answer 21

product of pro-glucagon gene
>also released from L cells in response to food ingestion
>inhibits gastric emptying and reduces food intake

Question 22

oxyntomodulin

Answer 22

from pro-glucagon gene and released from oxyntic cells and L-cells of small intestine after meal
>acts to suppress appetite - mechanisms and site unclear

Question 23

obestatin

Answer 23

peptide produced from gene that encodes ghrelin and released from cells lining stomach/small intestine
>sugested to reduce food intake - may act to antagonise the actions of ghrelin
>actions unclear at present

Question 24

what is ghrelin?

Answer 24

a hunger signal
> is an octanoylated peptide produced and secreted by oxyntic cells in stomach
>ghrelin levels increase before meals and decrease after meals
>levels are raised by fasting and hypoglycaemia
>peripheral ghrelin stimulates food intake, decreases energy expenditure and decreases fat utilisation
>ghrelin receptor-expressing neurons in hypothalamus help control fat metabolism increases lipogenesis and decrease lipid oxidation - prepare body to store energy

Question 25

hypothalamus and obesity

Answer 25

> overall energy balance is controlled by feedback loops which act to maintain constancy of total body energy stores
>signals are produced in response to body nutritional status
> these are sensed in the hypothalamus
> act to modulate food intake and energy expenditure

Question 26

what are the central appetite controllers

Answer 26

> glutamate, gaba and opioids

>monoamines

Question 27

monoamines

Answer 27

they act to suppress food intake - many drugs developed to anti on these systems - most withdrawn due to side effects

Question 28

glutamates Gaba and opioids

Answer 28

increase food intake when injected into hypothalamic centres - effects are modest

Question 29

what are the two hormones that act on hypothalamic neurones

Answer 29

LEPTIN and INSULIN
>adiposity signals
>they are produced in peripheral tissues
>report fat status to brain

Question 30

hormone function

Answer 30

inform brain to alter energy balance - eat less and increase energy burn and this malfunctions in an obese state

Question 31

leptin (reduced)

Answer 31

reduced leptin mimics starvation causing unrestrained appetite

Question 32

no leptin receptor

Answer 32

whole body loss of leptin signalling results in severe obesity

Question 33

leptin

Answer 33

> circulates in proportion to body adiposity
high levels of receptors in the hypothalamus
intracerebroventricular leptin inhibits food intake and decreases body weight of rodents

Question 34

biological roles of leptin

Answer 34

> food intake/energy expenditure/fat deposit
peripheral glucose homeostasis/insulin sensitivity
maintenance of immune system
bone formation
>and an area of other things

Question 35

treating obesity !

Answer 35

recombinant leptin therapy works in obese humans

Question 36

is leptin therapy common ?

Answer 36

> it is limited by severe leptin resistance present in most obese individuals
vast majority of human obesity is characterised by high leptin levels

Question 37

what does diet induced obesity result in

Answer 37

results in leptin resistance !

perhaps due to:

1) defective lepton transport into the brain
2) altered signal transduction following leptin binding to its receptor

Question 38

previous drugs for treating obesity ?

Answer 38

>noradrenergics 
>serotonergics 
>Fen-Phen
>sibutramine
>rimonabant

Question 39

noradrenergics

Answer 39

they are appetite suppressants acting to inhibit noradrenaline uptake
-can have a CV side effects

eg
>diethylproprion
>manzindol
>phentermine

Question 40

serotonergics

Answer 40

they are appetite suppressants acting on the 5-HT system
>fenfluramine and dexflenfluramine are no longer used due to induced heart disease

eg.
fenfluramine
dexflenfluramine
fluoxetine

Question 41

Fen-Phen

Answer 41

is a combination of fenfluramine and phentermine

>is very effective but potentially causes fatal pulmonary hypertension and heart valve problems

Question 42

sibutramine

Answer 42

Selectively inhibits re-uptake of noradrenaline, 5-HT and dopamine
Decreases food intake and may also increase thermogenesis.
Effective - though limited - modest weight loss (10lbs in 1 year)
Major concerns over side-effects (cardiovascular events and strokes)
Withdrawn (2010), but can be purchased – weight loss products on-line

eg
meridia
reductil

Question 43

rimonabant

Answer 43

Antagonist of CB1 receptors – high levels in hypothalamus
Counteracts obesity; potential effectiveness to assist smokers to quit
and reduce addiction to certain drugs (ethanol, cocaine and opiates)
and to improve short-term memory
Approved for use in EU in 2006 for obesity (FDA did not approve in 2007)
Reports of severe depression and anxiety in some patients (suicide risk)
As endocannabinoids neuroprotective – worries about neurodegeneration
2008/9: Rimonabant sales suspended/drug withdrawn

eg
acomplia

Question 44

over the counter drug

Answer 44

orlistat
>Inhibits pancreatic lipase decreasing triglyceride absorption
reduces efficiency of fat absorption (by ~30%) in small intestine
Side-effects include cramping, bloating, flatulence, abdominal
pain and diarrhoea
Need to take vitamin supplements (loss of fat soluble vitamins – e.g. A,D,E)
Not particularly effective over long-term (3 kg in 12 months)
Tendency to get ‘rebound’ in weight

Question 45

upcoming anti-obesity drugs

Answer 45

liraglutide

Question 46

bariatric surgery

Answer 46

is a gastric by-pass surgery - produces substantial weight loss
>surgery induce high level of complete resolution of Type II diabetes
>bypass restricts calorie intake and induces malabsorption of nutrients but resolution of TIID is not simply due to decreased energy intake
>changes in the gut microbia, altered circulating bile acids and short chain FAs

Question 47

adaptive thermogenesis

Answer 47

adult humans possess BAT, BAT dissipates energy as heat, inducible ‘browning” of WAT
>thermogenic adipocytes - increase energy expenditure uncoupling of oxidative metabolism from ATP production
>key function of uncoupling protein 1 (UCP1) fatty acid activated protein short circuits proton gradient in mitochondria - accelerating fuel oxidation - produces heat