CH. 9-10 FAT METABOLISM

Where is fat stored in the body? Name the different sources and their relative abundance.

1. Adipose tissue: The majority of fat in the body is stored in adipose tissue, which is found beneath the skin (subcutaneous) and around organs (visceral). Subcutaneous fat is the fat you can see and feel just beneath the skin, while visceral fat is located deep inside the body around vital organs like the liver, pancreas, and intestines. 2. Muscle tissue: Intramuscular fat is stored within muscle fibers and can account for a small amount of total body fat. 3. Liver: The liver can store a small amount of fat, but excessive fat accumulation in the liver can lead to a condition called non-alcoholic fatty liver disease (NAFLD). The relative abundance of fat in these different sources can vary depending on various factors, including genetics, age, sex, and lifestyle habits. However, adipose tissue is the primary site of fat storage in the body, accounting for the majority of total body fat.

Give a general overview of the 7 steps of fat metabolism

1. Lipolvsis 2. Removal of FA from adipose cell 3. Transport of FA in bloodstream Entry of FA into muscle cell Transport of FA into mitochondria B-oxidation TCA cycle, electron transport chain

9 T.H. (8mph) (7mph) (More) (Worse)

According to the graph below, in January 2020 this athlete's crossover point occurs at (___mph) and in October 2020, her crossover point occurs at (__mph). In October 2020, when running at 9mph, she relies (___) on carbohydrate oxidation thank she did in January. Assuming that she did not drastically change her diet, her current state of aerobic training (in October) is likely (___) than in January.

9 T.H. At approximately what relative intensity would a well trained endurance athlete attain their maximal rates of fat oxidation (e.g g/min of fat oxidized)?

At 60 - 65% of VO2max, where energy needs are relatively high, combined with adequate delivery of fatty acids to the muscle

What is beta oxidation? What does it produce?

Beta oxidation is the process of breaking down fatty acids into acetyl-CoA molecules, which can be further metabolized in the citric acid cycle to produce energy in the form of ATP. During beta oxidation, the fatty acid is broken down in a series of steps that involve the removal of two carbon units at a time, producing acetyl-CoA, NADH, and FADH2 as byproducts. These products can then enter the electron transport chain to produce ATP through oxidative phosphorylation. Beta oxidation is an important process for energy production during periods of prolonged exercise or fasting, when the body relies on stored fat as a fuel source.

9 T.H. The majority of fatty acids in the blood are:

Bound to albumin

What is the role of carnitine in fatty acid transport into the mitochondrial matrix?

Carnitine plays a crucial role in transporting long-chain fatty acids into the mitochondrial matrix for oxidation. In the cytosol, the long-chain fatty acids are activated by attaching to coenzyme A (CoA) to form fatty acyl-CoA, which then requires carnitine to transport across the inner mitochondrial membrane. The enzyme carnitine palmitoyltransferase I (CPT-I) catalyzes the transfer of the fatty acyl group from CoA to carnitine, forming fatty acyl-carnitine. Fatty acyl-carnitine then crosses the inner mitochondrial membrane via a translocase, where carnitine palmitoyltransferase II (CPT-II) catalyzes the transfer of the fatty acyl group back to CoA, releasing the carnitine molecule. The fatty acyl-CoA can then undergo beta-oxidation to produce acetyl-CoA for entry into the citric acid cycle and subsequent ATP production through oxidative phosphorylation.

Why does FFA appearance in the blood increase from rest to moderate exercise?

During rest, the body predominantly relies on glucose as the primary fuel source for energy production. However, as exercise intensity increases from rest to moderate, there is an increased demand for energy to fuel working muscles. This increased energy demand triggers the breakdown of triglycerides in adipose tissue through the process of lipolysis, which leads to the release of free fatty acids (FFAs) into the bloodstream. The FFAs are then transported to the working muscles, where they can be taken up and used as a source of fuel for energy production. Therefore, the appearance of FFAs in the blood increases from rest to moderate exercise due to the body's increased reliance on fat as a fuel source to meet the energy demands of the exercising muscles.

9 T.H. Which hormones activates lipolysis in adipose tissue?

Epinephrine

9 T.H. Which of the following are considered significant limiting factors in how quickly we utilize fat during high intensity exercise?

Fatty acid transport into the mitochondria

What is lipolysis, name the main enzyme responsible for it and the physiological states that activate it.

Lipolysis is the breakdown of stored triglycerides (triacylglycerols) into their component fatty acids and glycerol molecules. The main enzyme responsible for lipolysis is hormone-sensitive lipase (HSL), which is primarily found in adipose tissue. Lipolysis is activated by a decrease in insulin and an increase in the levels of certain hormones, such as catecholamines (epinephrine and norepinephrine) and glucagon. These hormones bind to specific receptors on adipose tissue cells and activate adenylate cyclase, which increases levels of the intracellular signaling molecule cyclic AMP (cAMP). This, in turn, activates protein kinase A (PKA), which phosphorylates HSL and activates it. Lipolysis can also be stimulated by exercise, especially endurance exercise, which can increase levels of circulating catecholamines and stimulate lipolysis in adipose tissue.

How are most fatty acids transported in the blood, from the adipocyte to the muscle?

Most fatty acids are transported in the blood bound to albumin, a protein in the plasma. The fatty acids are released from adipose tissue into the bloodstream and bind to albumin for transport to the muscle tissue. Once the fatty acids reach the muscle cells, they can be taken up and used for energy production.

How does the fatty acid get "activated" once inside the cell, for transport into mitochondrion?

Once inside the cell, the fatty acid is activated by converting it into fatty acyl-CoA through the action of an enzyme called fatty acyl-CoA synthetase. This reaction requires energy from ATP and CoA and results in the formation of fatty acyl-CoA, which can then be transported into the mitochondrion for oxidation.

What is reesterification and why does it occur?

Reesterification is the process by which fatty acids are recombined with glycerol to form triglycerides, which are then stored in adipose tissue or used as a source of energy. Reesterification occurs because fatty acids released during lipolysis cannot be used directly for energy production in many tissues. Instead, they are carried to the liver, where they undergo beta-oxidation to produce ATP for energy production or are converted to ketone bodies that can be used as an energy source by other tissues. However, in the presence of excess energy or when energy demands are low, the liver may recombine these fatty acids with glycerol to form triglycerides, which are then transported back to adipose tissue for storage. Reesterification is an important process for maintaining energy balance and preventing excessive buildup of free fatty acids in the circulation, which can be detrimental to metabolic health.

What hormones activate or inhibit lipolysis?

The breakdown of stored triglycerides (lipolysis) in adipose tissue is regulated by a complex interplay of hormones. The primary hormones that activate lipolysis are catecholamines (such as epinephrine and norepinephrine) and glucagon. These hormones bind to specific receptors on adipose tissue cells and activate adenylate cyclase, which increases levels of the intracellular signaling molecule cyclic AMP (cAMP). This, in turn, activates protein kinase A (PKA), which phosphorylates hormone-sensitive lipase (HSL) and activates it, leading to the breakdown of stored triglycerides into fatty acids and glycerol. Other hormones that can stimulate lipolysis include growth hormone, cortisol, and thyroid hormone. In contrast, insulin is a hormone that inhibits lipolysis, as it promotes fat storage and reduces the availability of stored triglycerides for breakdown. Leptin, a hormone produced by adipose tissue, can also have inhibitory effects on lipolysis.

Which enzyme is considered the rate-limiting enzyme in fatty acid oxidation?

The enzyme carnitine palmitoyltransferase I (CPT1) is considered the rate-limiting enzyme in fatty acid oxidation.

What is the major factor influencing the removal of FA's from the fat cell? Why is it compromised during very strenuous exercise?

The major factor influencing the removal of fatty acids from fat cells is the activity of hormone-sensitive lipase (HSL). HSL is activated by hormonal signals such as adrenaline, glucagon, and growth hormone, which increase the breakdown of triglycerides into free fatty acids and glycerol for use by other tissues. During very strenuous exercise, the availability of oxygen may become limited, leading to anaerobic metabolism and the buildup of lactate and hydrogen ions in muscle tissue. This acidic environment can inhibit the activity of HSL, making it more difficult for fatty acids to be released from adipose tissue and used as a fuel source. In addition, during high-intensity exercise, blood flow is directed towards the working muscles, and this reduced blood flow to adipose tissue may limit the delivery of hormones that stimulate HSL activity. Therefore, the removal of fatty acids from fat cells can be compromised during very strenuous exercise, leading to a greater reliance on other energy sources such as glycogen and glucose.

What is the rate limiting enzyme in B-oxidation and name 1 factor that promotes, and 1 factor that inhibits, its rate of activity.

The rate-limiting enzyme in beta-oxidation is carnitine palmitoyltransferase 1 (CPT1). CPT1 transfers the long-chain fatty acid into the mitochondrial matrix via the carnitine shuttle. One factor that promotes the rate of CPT1 activity is increased energy demand, which stimulates the production of CPT1 and the carnitine shuttle. One factor that inhibits CPT1 activity is high levels of malonyl-CoA, which is produced in the first step of fatty acid synthesis and inhibits CPT1 from importing more fatty acids into the mitochondria for oxidation.

9 T.H. When an individual exercises at their crossover point:

They obtain 50% of their energy from carbohydrate oxidation, and 50% from fat oxidation

Name 2 cell membrane proteins that play a role in taking up fatty acids from the blood into the muscle cell.

Two cell membrane proteins that play a role in taking up fatty acids from the blood into the muscle cell are Fatty Acid Transport Protein (FATP) and Fatty Acid Binding Protein (FABP).

9 T.H. Under which of the following conditions would you expect beta oxidation to slow down/ decrease?

When thiolase levels are low When Acetyl CoA levels are high When insulin levels are very high

10 T.H. A number of studies demonstrated that consuming a low carbohydrate, high fat diet results in increased fat oxidation rates during exercise, sparing muscle and liver glycogen during prolonged submaximal exercise (i.e. > 2hrs, around 50-65% of VO2max).Despite this improved ability to oxidize fat, why might following such a high fat, low carbohydrte diet not be helpful to elite marathoners' performance on race day?

a- Elite marathoners maintain a high % of their VO2max during a race - requiring a heavy reliance on CHO oxidation b- Chronically training with near glycogen depleted stores suppresses pyruvate dehydrogenase ctivity -which slows down how fast glucose can be utilized for energy c- Oxidizing fat requires a greater rate of O2 consumption compared to carbohydrate - a problem when racing at intensities close to VO2max

10 T.H. When assessing the rate of lipolysis, which metabolite appearing in the blood gives you the best representation of how quickly lipolysis is occurring?

b- Glycerol

10 T.H. Which of the following adaptations occur in muscle fibers as a result of endurance training, that allow an individual to increase their reliance on fat, while decreasing their reliance on carbohydrate, when exercising at a fixed submaximal intensity (i.e. jogging at 6 miles/hour)

bIncreased intramuscular triglyceride stores cIncreased mitonchondrial number and mass eIncreased fatty acid transporter density in muscle fIncreased capillarization in muscle

9 T.H. At very high exercise intensities, what factor(s) increasingly limit fat oxidation?

transport of fatty acids from adipose tissue to the muscle increased glycolysis and carbohydrate oxidation rates