Notes
Feed-Fast Cycle Part I
Sections
FAST CYCLE
- Short term or long term (starvation)
- Occurs after absorptive phase
- Insulin: glucagon ratio is low
- Catabolic processes dominate (nutrients mobilized from storage)
Body's objectives:
- Deliver glucose to brain and red blood cells
- Distribute remainder to the rest of the tissues (TAG & ketone bodies)
Timeline
- Hour 0: ingest meal
- Hour 4: glucose depletes, glycogen stores mobilized
- Hour 18: liver glycogen depletes --> gluconeogenesis --> TAG mobilization --> ketogenesis
- Hour 24: TAG mobilization & ketogenesis peak
Primary functions of each organ italicized for clarity.
LIVER: CENTRAL ROLE IN METABOLISM
- Nutrients drain from gut (primary nutrient source) to liver via hepatic portal vein
- Liver distributes nutrients to remaining organs
- Responds to needs of all organs
Fed state
Most anabolic and storage pathways
- Glucose (glycolysis, HMP shunt-->NADPH)): stored as glycogen
- Fatty acid synthesis (from glucose --> acetyl CoA)
- Chylomicron remnants: TAG synthesized and packaged into VLDL
- Amino acids (synthesis of proteins, pyruvate, acetyl CoA & CAC intermediates)
Fasting state
Responds to body's glucose needs
i. Glycogen --> glucose
ii. Gluconeogenesis: liver only
iii. Ketogenesis: liver only (cannot be used by liver for energy)
- Ketogenesis prevents degradation of essential proteins for gluconeogenesis
- Hepatocyte energy requirements met by fatty acid oxidation
- TAG --> Free fatty acids (--> ATP) + glycerol (--> gluconeogenesis)
BRAIN
Fed state
Glucose: primary energy source (glycolysis --> ATP)
Fasting state
- Glucose still primary energy source
- Extended fast: ketone bodies (can cross blood brain barrier)
ADIPOSE
Fed state
Fatty acids stored as TAG
- Glucose (glycolysis, HMP shunt-->NADPH)
- Fatty acid synthesis
- Chylomicrons (dietary TAG): degrade to chylomicron remnants
Fasting state
- TAG --> Free fatty acids (--> ATP in liver/muscle) + glycerol (--> gluconeogenesis in liver)
RESTING MUSCLE
Fed state
Glucose (glycolysis): stored as glycogen
Branched chain amino acids (preferentially): protein synthesis
- Chylomicrons (dietary TAG): degrade to chylomicron remnants
- Fatty acid oxidation (secondary energy sources)
- Energy needs change during exercise: primary metabolic function depends on own needs
Fasting state
- Muscle glycogen --> glucose (glycolysis)
- Muscle protein mobilized (gluconeogenic amino acids --> liver)
- As starvation progresses: fatty acid oxidation, ketone bodies
Full-Length Text
- Here we will learn the feed-fast cycle, which describes the integration of metabolic processes in different organs just after a meal, and also in the post-absorptive phase.
- This is part I of a two-part tutorial.
- We will learn the fed cycle, here, and the fast cycle in part II.
- To begin, let's draw the key organs involved in metabolic integration:
- the brain
- adipose tissue (a representative droplet)
- the liver
- and skeletal muscle (at rest).
- To understand the importance of the liver, let's show its role in nutrient dissemination to the general circulation.
- Re-draw the liver.
- Indicate that the gut (our primary source of nutrients) drains directly into the liver via the hepatic portal vein.
- From there, show that nutrients enter general circulation to distribute throughout the body.
- Thus, we can imagine that the liver (much like a king) governs the rest of the body's access to nutrients.
- In times of prosperity, the fed-state, king liver distributes nutrients to its subjects and stores what remains.
- In times of poverty, it allocates stored nutrients based on the needs of each organ.
- Now, start a table to learn some key points about the feed and fast cycles.
- Denote that the feed cycle is also called the absorptive cycle.
- It occurs 2-4 hours after a meal.
- Denote that during this period, the insulin to glucagon ratio is high, and anabolic (synthetic) processes dominate.
- Denote that most tissues use glucose for energy in this state.
- Denote that the fasting cycle can either be short term or long term (starvation) and that it occurs after the absorptive phase.
- Denote that the insulin to glucagon ratio is low, and that catabolic processes dominate.
Let's illustrate these two cycles and the metabolic responses of the key organs we have drawn.
Here, we'll illustrate the feed cycle.
- Draw an intestine.
- Show that after a meal, it contains the following:
- Glucose, the primary energy source of cells.
- Chylomicrons, which contain triacylglycerol.
- Amino acids.
We will see how each of these is metabolized in each organ.
Let's start with glucose.
- Show that glucose is distributed to all of these key organs.
- Now, draw a box for carbohydrates in each of the organs to learn how they each use glucose in the fed state.
- For the brain, write that glucose is its primary energy source.
- Show that here, glucose enters glycolysis to produce ATP.
- Now, indicate that glucose enters glycolysis in all of the remaining organs to produce energy in the fed state.
What about any excess glucose absorbed from the gut?
- Show that both the liver and muscle can store glucose as glycogen.
- Finally, show that both the liver and adipose tissue can shunt glucose to the hexose monophosphate pathway (HMP) to produce NADPH, which is used in many anabolic pathways.
- Show that both the liver and adipose tissue can use NADPH in one anabolic pathway in particular: fatty acid synthesis.
- Why do we list fatty acid synthesis in the carbohydrate box?
- Make a notation that acetyl CoA (glucose breakdown product) is a substrate for fatty acid synthesis.
- Thus, excess dietary carbohydrates can be stored as glycogen in the liver and muscle and as body fat in the liver and adipose.
Now, for chylomicrons.
- Draw a box for lipids in all the organs except for the brain.
- Again, the brain only uses glucose for energy in the fed state.
- Indicate that in skeletal muscle and adipose tissue (the peripheral tissues), chylomicrons are degraded to chylomicron remnants.
- Mammary glands also degrade chylomicrons, but we do not discuss this, here.
- As chylomicrons degrade to remnants, they deposit free fatty acids in these tissues, so indicate that fatty acid oxidation is a secondary source of energy for muscle cells (second to glucose).
- Indicate that adipose tissue can convert fatty acids to triacylglycerol for storage.
- Thus, excess dietary fat is stored in the adipose.
- Finally, indicate that the chylomicron remnants go to the liver.
- Write that the liver, like adipose tissue, also promotes triacylglycerol synthesis, but packages TAG into very low-density lipoproteins (VLDL).
- VLDL then distributes TAG and the rest of its lipid contents to the peripheral tissues.
Finally, amino acids.
- Draw a box for amino acids in the liver and skeletal muscle.
- Adipose tissue is not a primary site of protein synthesis, nor is the brain.
- Show that amino acids enter the liver, which uses them for protein synthesis.
- Show that it also uses the carbon skeletons of these amino acids to synthesize pyruvate, acetyl CoA and citric acid cycle intermediates.
- Excess amino acids are not stored by distributed to all the peripheral tissues.
- Show that the muscle takes up branched chain amino acids because the liver cannot deaminate them.
- In fact, the liver shunts branched amino acids to the peripheral tissues for this reason.
- Indicate that it synthesizes proteins from them.
Now, let's highlight the key roles of adipose tissue, muscle, liver, and brain.
- For adipose tissue, highlight storage: TAG.
- For resting-state muscle, highlight storage of glycogen and protein synthesis.
- However, write the caveat that the energy needs of skeletal muscle change during exercise, thus its primary metabolic function depends on its own needs.
- This is unlike the liver-king, which responds to the needs of all organs.
- In fact, most of the anabolic and storage pathways in the feed-cycle occur in the liver, so there is nothing in particular to highlight for it.
- Brain, on the contrary is quite simple – it depends on glucose, a concept we'll explore further in the fasting cycle.