Exercise Metabolism: RER and Hormonal Regulation of Plasma Glucose

Fuel sources and energy systems in exercise

  • Bioenergetics overview: the body uses macronutrients as fuels to make energy. Preferred fuels for ATP production are fats and carbohydrates; proteins are used less for energy.
  • Major energy systems for ATP production:
    • ATP-PC system (phosphagen system)
    • Glycolysis (anaerobic glucose breakdown)
    • Oxidative phosphorylation (aerobic) via the Krebs cycle and the electron transport chain (ETC)
  • The energy system predominance depends on exercise intensity and duration:
    • Low-to-moderate intensity relies more on fat oxidation and oxidative metabolism over time
    • High-intensity or longer-duration efforts shift the substrate mix toward carbohydrates as needed
  • The Respiratory Exchange Ratio (RER) is used to infer substrate use during steady-state or submaximal exercise.
    • RER estimates the relative contributions of carbohydrates and fats to energy metabolism
    • RER is calculated from gas exchange data collected during exercise

Respiratory Exchange Ratio (RER)

  • Definition and purpose
    • RER is the ratio of carbon dioxide production to oxygen consumption:
      RER=VCO<em>2VO</em>2RER = \frac{VCO<em>2}{VO</em>2}
    • It provides insight into the predominant fuel being oxidized (carbs vs fats) during steady-state exercise
  • Terminology and scope
    • Also called respiratory exchange ratio or non-protein R (R or non-protein R in some sources)
    • Non-protein R because it relates to carb and fat metabolism, not protein oxidation
  • How RER is measured
    • While exercising, you consume O2 and produce CO2; these can be measured with:
    • A metabolic cart (real-time VO2 and VCO2)
    • A Douglas bag technique (collect expired air, analyze O2 and CO2 concentrations)
  • What RER tells you about fuel use
    • RER values reflect relative proportions of fats and carbohydrates being burned for energy
    • RER should be measured at steady-state (not during maximal effort)
    • At maximal effort (VO2 max), RER can exceed 1.0 (often > 1.1) due to:
    • Increased CO2 production from buffering of metabolic acids and rapid, intense ventilation
    • Very high glycolytic flux and fast-fiber recruitment
  • Common interpretation table (conceptual)
    • RER ~ 0.70: nearly all fat oxidation
    • RER ~ 0.85: ~50% fat and ~50% carbohydrate (roughly balanced)
    • RER ~ 1.00: predominantly carbohydrate oxidation
    • Values between 0.70 and 0.85 indicate a mix skewed toward fat; values between 0.85 and 1.00 indicate a shift toward carbs
    • Example from the lecture: an RER of 0.75 can correspond to about 83% fat and 17% carbohydrate
  • Three checkpoint values to memorize (as given in the lecture)
    • 0.70: 100% fat contribution
    • 0.85: approximately 50/50 fat and carbohydrate
    • 1.00: 100% carbohydrate contribution
  • RER at rest and during low-intensity exercise
    • Rest (fasted): RER ~ 0.70 (predominantly fat metabolism)
    • Low-intensity exercise: still fat-dominant, but gradually increasing carbohydrate contribution as intensity rises
  • RER during higher-intensity exercise
    • Carbohydrate contribution increases with intensity
    • Stricter interpretation requires steady-state; at VO2 max, RER > 1.0 is common
  • Practical exam notes
    • You may be asked: what fuel source is predominant at a given RER value? (e.g., RER = 0.75 → mainly fats; RER = 0.90 → more carbs but still some fats)
    • You may be asked to state the “preferred fuel source” and whether it is in the bloodstream (e.g., plasma glucose) or in the muscle (e.g., muscle glycogen) or both
  • RER measurement caveats
    • RER reflects substrate oxidation from steady-state data, not necessarily the entire energy picture during non-steady or very short events
    • High-intensity data can produce RER values above 1.0 due to non-metabolic CO2 production (e.g., buffering) and rapid ventilation; interpret with caution

RER in the lab and calculation practice

  • Lab 1 concepts
    • Measure VO2 with a metabolic cart by having the subject exhale into a system that analyzes gas concentrations
    • Use a Douglas bag to collect expired air and analyze O2 and CO2 concentrations to derive VO2 and VCO2
  • Lab 2 practice
    • You will calculate RER from collected VO2 and VCO2 data (e.g., from daily Euclid or similar data sources mentioned in the course)
    • From the RER value, identify the predominant fuel (fat vs carb) and the preferred fuel source (blood vs muscle) during exercise

Fuel sources and the physiology of maintaining plasma glucose

  • Central theme: maintaining plasma (blood) glucose during exercise
    • Exercise increases energy demand; the body relies on both glucose and fat stores to meet ATP needs
    • It is essential to keep blood glucose available to all cells, not just exercising muscles, to prevent hypoglycemia and maintain function
  • Major mechanisms for maintaining plasma glucose
    • Glycogenolysis: breakdown of glycogen to glucose
    • Liver glycogen breakdown feeds glucose directly into the bloodstream
    • Muscle glycogen primarily supports the muscle that contains it and does not directly replenish blood glucose
    • Liver glycogen stores contribute to circulating glucose when needed
    • Gluconeogenesis: formation of new glucose
    • Substrates include amino acids, glycerol (from triglycerides), and lactate (lactate-to-glucose via the Cori cycle)
    • Happens primarily in the liver; outputs replenish blood glucose during prolonged exercise
    • Lipolysis: breakdown of triglycerides to freeing fatty acids and glycerol
    • Free fatty acids (FFAs) circulate in plasma and can be used by many cells for energy
    • Glycerol can be used as a substrate for gluconeogenesis in the liver
    • Decreased glucose utilization by cells (glucose sparing)
    • Some hormones decrease cellular glucose uptake or limit entry of glucose into cells, thereby sparing glucose for critical tissues (e.g., brain)
    • One of the hormones discussed is described as directly blocking glucose entry by reducing glucose transporters on cells (GLUTs)
  • Hormonal coordination to maintain plasma glucose (overview)
    • A group of hormones acts to promote glycogenolysis, gluconeogenesis, and lipolysis, while modulating glucose uptake by tissues
    • The hormonal response is layered by acting time scale and mechanism (permissive, slow-acting, fast-acting)

Hormones relevant to exercise and plasma glucose maintenance

  • Hormones to know (as listed in the course):
    • Thyroid hormones: T3 and T4 (collectively referred to as thyroid hormones)
    • Cortisol
    • Growth hormone (GH)
    • Epinephrine (adrenaline) and norepinephrine (noradrenaline)
    • Insulin
    • Glucagon
  • Core themes about these hormones
    • Hormones have target tissues and trigger specific responses that affect energy metabolism during exercise
    • The same hormones contribute to maintaining plasma glucose, but their specific actions and timescales differ
  • Key structural concept: permissive vs fast-acting vs slow-acting hormones
    • Permissive hormone: thyroid hormone (does not directly cause lipolysis but increases action of other hormones by increasing receptor availability or sensitivity)
    • Slow-acting hormones: cortisol and growth hormone (their effects develop more slowly and contribute to longer-term adaptations, tissue repair, and glucose production)
    • Fast-acting hormones: epinephrine, norepinephrine, and glucagon (rapidly mobilize fuels and adjust glucose availability during exercise)
  • Insulin and glucagon (brief note)
    • Insulin generally lowers blood glucose by promoting glucose uptake and storage; glucagon raises blood glucose by promoting glucose production; their precise roles during exercise are part of the hormonal regulation discussion (insulin is not described in depth in this transcript excerpt)

Thyroid hormone (permissive) details

  • Release site: thyroid gland; primarily T3 and T4
  • Physical properties: lipid-soluble; carried in the blood by carrier proteins; a portion is unbound as 'free hormone' and can enter cells
  • Stimulus for release: decreased circulating thyroid hormone levels trigger release to replenish
  • Primary action: permissive effect; increases action of other hormones by increasing receptor number or receptor sensitivity
    • Example: increases beta-adrenergic receptors on adipocytes for epinephrine, enhancing lipolysis when epinephrine is present
  • Exercise-specific response
    • During exercise, free thyroid hormone levels in the blood rise (free hormone concentration increases) as more hormone is mobilized and enters tissues
    • The thyroid gland increases secretion to replenish free hormone as needed
  • Overall significance for exercise
    • Does not directly cause lipolysis; rather amplifies the effects of other hormones that mobilize fats, thereby supporting energy supply during activity

Cortisol (slow-acting)

  • Source: adrenal cortex
  • Triggers: stress and exercise (and daily fluctuations in cortisol levels)
  • Primary actions relevant to exercise
    • Mobilizes amino acids and fatty acids for energy
    • Stimulates gluconeogenesis (glucose production in the liver)
    • Stimulates glycolysis (in some contexts) and lipolysis; can block glucose entry/utilization in tissues
  • Exercise response and timing
    • Cortisol tends to increase with higher exercise intensity and with longer duration
    • Morning cortisol spikes; exercising can elevate cortisol compared with a non-exercise day at the same time of day
    • Cortisol is slow-acting and largely contributes to post-exercise repair and longer-term metabolic adjustments via changes in DNA activity (lipolysis, gluconeogenesis, and protein metabolism)
  • Additional notes
    • Cortisol can influence protein breakdown to provide substrates for gluconeogenesis (amino acids)
    • The hormone is described as helping with tissue repair after exercise via its genomic effects (lipolysis and glucose production are part of its broader role)

Growth hormone (slow-acting)

  • Source: anterior pituitary
  • Triggers: exercise is a strong stimulator; also stimulated by sleep, low glucose, and other stressors
  • Primary actions relevant to exercise
    • Stimulates protein synthesis and growth (anabolism) to support muscle repair and remodeling
    • Promotes gluconeogenesis and lipolysis; can decrease glucose utilization by tissues (insulin resistance effects)
  • Exercise response and timing
    • Increases with exercise intensity and duration
    • Athletes may show higher GH responses during exercise compared with untrained individuals
  • Overall significance
    • GH supports long-term adaptation and tissue repair; like cortisol, it is slow-acting but contributes to maintaining plasma glucose and energy substrate availability

Epinephrine, Norepinephrine (fast-acting) and Glucagon

  • Fast-acting catecholamines (epinephrine and norepinephrine)
    • Rapidly mobilize fuels to meet sudden energy demands during exercise
    • Promote glycogenolysis and lipolysis; increase blood glucose availability and plasma free fatty acids
    • Immediate effects help sustain performance at higher intensities
  • Glucagon (fast-acting)
    • Raises blood glucose by promoting hepatic glucose production (glycogenolysis and gluconeogenesis)
    • Acts quickly to support energy supply during exercise, especially when blood glucose would otherwise fall
  • Overall role during exercise
    • Together with cortisol and GH, these fast-acting hormones help ensure a rapid, adequate energy supply during variable exercise intensities
    • They also interact with insulin to maintain glucose homeostasis and to modulate substrate use based on energy demands

Glucose homeostasis during exercise: practical implications

  • Long-duration exercise and hypoglycemia risk
    • If exercise continues long enough, plasma glucose can deplete; hepatic glucose output and gluconeogenesis must compensate to maintain blood glucose for all cells
    • Muscle glycogen can provide a local fuel source, but circulating glucose becomes increasingly important for non-muscle tissues and ongoing activity
  • Lipolysis and substrate switching
    • Lipolysis provides FFAs as an energy source, sparing plasma glucose for cells that rely on glucose (e.g., brain)
    • As intensity increases, carbohydrate contribution rises while fat contribution falls, as reflected by rising RER values
  • Fuel mixture and training implications
    • Endurance training can enhance lipid oxidative capacity and spare glycogen; hormonal responses adapt with training to optimize fuel use
    • Understanding RER and hormonal regulation helps in planning fueling strategies for events of different durations and intensities

Practical exam tips and connections to prior lectures

  • Be able to explain what RER measures and how it is calculated:
    • From respiratory gas measurements: RER=VCO<em>2VO</em>2RER = \frac{VCO<em>2}{VO</em>2}
  • Know how to interpret RER values and what they imply about fat vs carb oxidation. Remember the three checkpoints:
    • 0.70 (mostly fats)
    • 0.85 (roughly 50/50)
    • 1.00 (mostly carbs)
  • Understand why RER can exceed 1.0 during maximal effort and what this indicates about metabolism and ventilation, not just fuel use
  • Recall the main fuel substrates and how the body makes them available during exercise:
    • Glycogenolysis (liver glycogen → glucose in blood)
    • Gluconeogenesis (from amino acids, glycerol, lactate)
    • Lipolysis (triglycerides → FFAs and glycerol) and use of FFAs by cells
  • Memorize the basic roles and timing of the hormones discussed: thyroid (permissive), cortisol (slow, gluconeogenesis and lipolysis), growth hormone (slow, protein synthesis, gluconeogenesis, lipolysis), epinephrine/norepinephrine (fast, glycogenolysis and lipolysis), glucagon (fast, raises blood glucose), insulin (not detailed here)
  • Note the practical lab connections: lab 1 (VO2 and VCO2 via metabolic cart and Douglas bag) and lab 2 (calculating RER from data) and how these feed into understanding fuel use in real humans
  • Conceptual links to foundational physiology: energy systems, substrate utilization, and hormonal regulation under physical stress; emphasize how these mechanisms ensure continued energy supply and organismal homeostasis during varied exercise scenarios