4 - Liver Function and Nutritional States in the Starve:Feed Cycle

Question 1

How are nutrients delivered to the liver and what is the exception?

Answer 1

Absorbed in small intestine into the blood stream and enters liver via hepatic portal vein, except dietary fats

Question 2

What are some of the metabolic functions the liver carries out?

Answer 2

• Storage of glycogen; regulation of homeostasis; conversion of fructose and galactose
• Synthesis and oxidation of fatty acids and formation of ketone bodies (liver does not store significant triglyerides)
• Oxidation of amino acids with the formation of urea
• Modification of steroids, hormones and xenobiotics
• Production and recycling of bile salts
• Maintains energy supply to body tissues under various healthy nutritional and disease states

Question 3

The majority of the livers energy demand is met by the oxidation of glucose.
True or false? + explain

Answer 3

False

Amino acids

Question 4

Excess carbohydrate is converted to fat during ‘well fed’ conditions.
True or false? + explain

Answer 4

True

Question 5

Majority of glucose entering the liver immediately after a meal is not stored but is distributed to other tissues.
True or false? + explain

Answer 5

True

GLUT2 = low affinity

Question 6

During fasting conditions the brain is able to oxidise fatty acids to derive energy.
True or false? + explain

Answer 6

False
Technically speaking it can but transport is limited, so generally false
Mainly ketone bodies

Question 7

Oxidation of FFA during fasting conditions provides substrates for gluconeogenesis.
True or false? + explain

Answer 7

False

Question 8

Excess amino acids provide substrates for fatty acid synthesis during ‘well-fed’ conditions.
True or false? + explain

Answer 8

True

Question 9

Amino acids provide substrates for gluconeogensis during fasting conditions.
True or false? + explain

Answer 9

True

Majority of amino acids can, main one being alanine

Question 10

What does the brain require for energy?

Answer 10

Glucose and oxygen

Question 11

What is the purpose of adipose tissue?

Answer 11

a long term energy store; brown fat has an important thermogenic role

Question 12

What do the kidneys require for energy?

Answer 12

actively consume oxygen

filter about 800 litres of blood a day to provide 200 litres of filtrate which reduces to ~ 2 litres of urine

Question 13

How does Metabolic specialisation arise in organs/tissues?

Answer 13

Differential gene expression

Each system has its particular set of enzymes and transporters

Question 14

Why is inter-organ/tissue cooperation of metabolic processes essential?

Answer 14

• Maximise nutrient storage during ‘well fed’ conditions
• Maintain energy supply during ‘starved’ or ‘fasting states’
• Respond quickly to changes in nutrient supply/demand
• Response to prolonged or severe changes

Question 15

Describe and draw the Cori Cycle

Answer 15

glucose recycling
no net gain of glucose
in starvation
Interrupted in well-fed state

Question 16

Describe and draw the Glucose:Alanine Cycle

Answer 16

prolonged fasting

from protein degradation

Question 17

Describe and draw the Glucose:Fatty Acid Cycle

Answer 17

Fatty acid oxidation can “spare” glucose oxidation (glycolysis)

Question 18

Describe what happens during the Well-Fed state, draw out what happens to each nutrient in each organ

Answer 18

Glucose and amino acids enter the blood stream and reach the liver via the portal vein

Dietary triacylglycerol is packed into chylomicrons

Insulin is secreted to stimulate the storage of fuels

Glycogen synthesis occurs in liver and muscles

Glycolysis occurs in the liver which generates acetyl-

CoA for fatty acid synthesis

FFAs produced by the liver are converted to TAG and packaged into VLDL particles

Insulin promotes FFA hydrolysis and uptake into adipose by activating lipoprotein lipase in adipose

Glucose uptake into muscle from GLUT4 translocation

Question 19

What happens to glucose going from well-fed to fasting?

Answer 19

the graph slide 12

Question 20

Describe what happens during the Early Fasting state (post absorption), draw out what happens to each nutrient in each organ

Answer 20

Blood glucose levels drop and glucagon is secreted

Glycogenolysis is stimulated to release glucose

Glucose is taken up primarily by the brain

Gluconeogenesis is stimulated

Main source of gluconeogenic precursors provided from the glucose:alanine cycle and Cori cycle

Recall: Cori cycle ‘recycles’ glucose via lactate (no net output)

Question 21

Describe what happens during the Fasting state, draw out what happens to each nutrient in each organ

Answer 21

Liver will deliver ~130mg/min glucose
~80mg from glycogen (initially)

Glucose is no longer taken up by the muscles

Low insulin levels reduces activity of LPL whilst hormone sensitive lipase (HSL) becomes active

Hydrolysis of stored TAG
FFAs used for energy or ketogenesis
Glycerol for gluconeogensis

The brain begins to rely more upon ketone bodies

Muscles use fatty acids and ketone bodies (glucose:fatty acid cycle ‘spares’ glucose for the brain)

Proteins are broken down, leading to atrophy

Amino acids (particularly alanine and glutamine), lactate and glycerol are all used to maintain a supply of glucose for the brain

Long-term starvation leads to brain malfunction

Question 22

What are the three main substrates for gluconeogenesis?

Answer 22

Alanine, lactate, glycerol

Question 23

How does the insulin:glucagon ratio affect hormones and metabolic fuels in the blood?

Answer 23

Slide 17 graph 
drop insulin and raise in glucagon
  --> rise in breakdown of fatty acids 
  --> drop in glucose
ONLY at lowest levels of insulin -> rise in ketone bodies (ketogenesis)
drop in glycogen

Question 24

Describe what happens during the Early Refed state (absorption)

Answer 24

Insulin is secreted in response to rising [glucose]

Liver maintains gluconeogenesis and diverts glucose to other organs and peripheral tissues

Glucose from gluconeogenesis is used to build up glycogen stores before dietary glucose is available

Excess glucose is converted into fat for storage

Question 25

Metabolic pathways in the liver of a well-fed person?

Answer 25

Glycolysis
glycogenesis
lipogenesis

Question 26

Metabolic pathways in the liver of a fasting person?

Answer 26

Gluconeogenesis,
ketogenesis
lipolysis
glycogenolysis
proteolysis

Question 27

Name 5 mechanisms which Homeostasis is regulated by the liver

Answer 27

Tissue-specific and cellular-specific (compartmentation) expression

Induction of enzymes (gene expression; prolonged changes)

Covalent modification

Allosteric effectors

Substrate availability

Question 28

Briefly outline the principle metabolic functions of the liver during well fed and fasting conditions

Answer 28

Think

Question 29

Discuss the role of the liver in coordinated metabolic processes in the starve:feed cycle

Answer 29

Think

Question 30

Discuss the importance of the Cori cycle and glucose:alanine cycles during mild fasting conditions

Answer 30

Think

Question 31

Describe how the insulin:glucagon ratio is responsible for controlling the uptake and liberation of FFAs from adipose during well fed and starved conditions

Answer 31

Think

Question 32

“High fat, low carb diets are better for weight loss” do you agree with this statement? In terms of the active processes in and between tissues, discuss the possible metabolic consequences of such a diet and any effects in terms of weight loss

Answer 32

Think