MED213: Fat Metabolism Notes

Relevance of Lipids in Sports and Exercise

• Lipids cannot be used for high-intensity exercise.

• They are utilized between exercise bouts and during recovery from prolonged exercise.

• Lipid metabolism is aerobic.

• Fatty acids, stored as triglycerides and triacylglycerols in adipose tissue and muscle, provide energy.

• As exercise intensity increases, fat usage decreases (Rapoport, 2010).

• As exercise duration increases, fat oxidation increases (Powers & Howley, 2012).

• Hormonal changes, especially insulin levels, regulate fat oxidation:

  • High insulin levels after a meal inhibit fatty acid availability.

  • Low insulin levels remove this inhibition.

Metabolism and Fuel Selection

Lipolysis

• Lipolysis is the breakdown of triglycerides into glycerol and fatty acids.

• Triglycerides are initially broken down in the mouth, stomach, and small intestine (via bile salts).

• The resulting fatty acids are then repackaged as lipoproteins for transportation.

• Lipolysis requires the activation of several key enzymes:

  • Adipose triglyceride lipase (ATGL)

  • Hormone-sensitive lipase (HSL)

  • Monoacylglycerol lipase (MGL)

• The process can be summarized as follows:

  • \text{Triacylglycerol} \xrightarrow{\text{ATGL}} \text{Diacylglycerol} + \text{Fatty acid}

  • \text{Diacylglycerol} \xrightarrow{\text{HSL}} \text{Monoacylglycerol} + \text{Fatty acid}

  • \text{Monoacylglycerol} \xrightarrow{\text{MGL}} \text{Glycerol} + \text{Fatty acid}

Lipolysis Location and Timing

• Lipolysis occurs in both adipose tissue and skeletal muscle.

• Lipoproteins (e.g., LDL/VLDL) contain triglycerides and are broken down by lipoprotein lipase (LPL).

• Adipocytes absorb these products after eating, while muscle cells absorb them during exercise.

• Lipolysis is suppressed within 1-2 hours of eating, especially after consuming high-carbohydrate foods (Lee et al., 2012).

Metabolic Pathways

• Glycogen:

  • Can be broken down into Glucose.

  • Glucose can undergo Glycolysis to form Pyruvate.

  • Pyruvate is converted to Acetyl-CoA.

• Triglycerides:

  • Broken down via lipolysis into Fatty Acids and Glycerol.

  • Fatty acids undergo β-oxidation to form Acetyl-CoA.

  • Glycerol can undergo gluconeogenesis, glycolysis or glycogenesis

• Acetyl-CoA

  • Enters the TCA cycle (Citric Acid Cycle).

  • The TCA cycle leads to the generation of NADH/FADH2.

  • NADH/FADH2 are used in the electron transport chain for ATP synthesis.

Fuel Selection

• When fasted, the body oxidizes stored energy (Duivenvoorde et al., 2015 - mice study).

• The respiratory exchange ratio (RER) decreases as fat metabolism increases.

• Upon food intake, especially carbohydrates (CHO), CHO metabolism increases.

Implications for Exercise

• For performance training, CHO is beneficial.

• To maximize fat burning, avoid exogenous fuel (CHO) intake.

Fatmax

• Fatmax is the exercise intensity at which maximal fat oxidation occurs.

• Typically, Fatmax occurs at 50-70% of VO2max.

• Fatmax is determined by measuring VO2/VCO2 or RER.

Exercise Training and Lipid Metabolism

Impact of Endurance Training

• Endurance training increases the contribution of fat to energy expenditure during endurance exercise.

• It increases oxidation of muscle-derived fat sources which lowers reliance on CHO, preserving muscle glycogen (Schrauwen et al., 2002).

Molecular Adaptations

• Endurance training decreases skeletal muscle mRNA expression for ACC2 (lipid synthesis).

• It also increases skeletal muscle mRNA expression for LPL (lipid hydrolysis/breakdown).

Fasted vs. Fed Exercise

• Consuming breakfast before exercise increases glucose utilization (Edinburgh et al., 2018).

• Exercising in a fasted state almost doubles fat oxidation compared to exercising after breakfast.

High-Fat Feeding for Performance

• While fasting increases fat oxidation, high-fat feeding does not necessarily improve performance (Cao et al., 2021).

• A 2005 meta-analysis showed a moderate negative effect of a high-fat diet on time to exhaustion (Erlenbusch et al., 2005).

Lipid Storage in Skeletal Muscle

• Lipids are located within the mitochondrial network in skeletal muscle (Daemen et al., 2018).

• Lipid droplets are positioned near mitochondria to facilitate fatty acid delivery to mitochondria when energy demands are high.

• Eccentric muscle damage can disrupt lipid metabolism, leading to increased muscle lipid content (Xu et al., 2012).

Lipid-Induced Insulin Resistance

• The Randle cycle (glucose-fatty acid cycle) explains how the body prioritizes either fat or carbohydrate metabolism.

• If glucose is available, there's negative feedback on fat metabolism (Samuel et al., 2019).

Mechanism of Insulin Resistance

• Normal: GLUT-4 translocation allows glucose uptake in skeletal muscle.

• Insulin Resistance (T2D): IRS-1 inhibition impairs GLUT-4 translocation, reducing glucose uptake (Samuel et al., 2019).

The Athlete's Paradox

• In obesity and type II diabetes, high muscle lipid content is associated with insulin resistance.

• Athletes accumulate a greater amount of lipid droplets in muscle, similar to obese and diabetic individuals.

• However, athletes remain insulin sensitive, hence the 'Athlete’s Paradox'.

Lipid Content Analysis

• Endurance athletes have similar intermyofibrillar lipid levels as patients with T2D.

• Lipid droplets in athletes are smaller, providing a larger surface area for lipolysis (Li et al., 2019).

• Athletes have the greatest amount of intramyocellular lipid, especially in type I muscle fibers.

• Absolute lipid droplet size is greater in type II diabetes (Daemen et al., 2018).

Turnover is Key

• In athletes, lipids are rapidly oxidized to produce ATP.

• In obesity/diabetes, lipids accumulate, are partially oxidized, and form bioactive lipid species (Coen et al., 2012).

Reducing Lipid Droplets

• Training programs in T2D can reduce lipid droplet size, though it is difficult to reduce lipid droplet number (Daemen et al., 2018).

• Reducing lipid droplet size improves glycemic control.