Evaluating Metabolic Health in Individuals With Extreme Obesity

24-hour energy expenditure will be assessed from participants spending 23 hours in a metabolic chamber.

This will be collected from the 23-hour chamber stay during Visit 2, Day 2. Specifically, this represents the total grams of fat oxidized over the 23-hour stay, calculated from indirect calorimetry stoichiometry.

This represents the amount of energy expended under strict basal conditions: post-absorptive (typically 10-12h fasted), thermoneutral, fully awake but supine and motionless, no recent physical activity. This will be collected from the 23-hour metabolic chamber stay.

This is the energy expended at rest but under less stringent conditions than basal: seated or supine, awake, post-absorptive but with less rigor about prior activity, temperature, and emotional state. This will be collected from the 23-hour metabolic chamber stay.

This is the energy expenditure during sleep, typically computed from the lowest stable ~3-hour window between roughly 02:00 and 05:00 when arousal and movement are minimal. Per our Standard Operating Procedures, this will be computed between 01:00 and 05:00.

This represents the postprandial rise in energy expenditure above the pre-meal baseline, integrated over the period until energy expenditure returns to baseline (typically 4-6 hours for a mixed meal). This reflects the energy cost of digestion, absorption, and substrate processing, plus a sympathetic activation component.

This is the energy expended on non-volitional movement: fidgeting, postural adjustments, small spontaneous movements during otherwise sedentary periods in the chamber. It is commonly measured by radar/Doppler motion sensors and quantified either as a fraction of chamber time active (% activity) or as the energy cost of activity above sleeping metabolic rate.

This is the gold-standard free-living EE measurement: participants drink a dose of ²H₂¹⁸O, and the differential elimination rates of the two isotopes over ~7-14 days yield CO₂ production and therefore EE under habitual living conditions. It captures everything the chamber misses: occupational and recreational activity, environmental temperature variation, real meal patterns.

This is the amount of minutes from meal ingestion until RER first reaches (or crosses) the meal's FQ. This represents the speed of the switch of fuel oxidation rather than its endpoint. A flexible system gets there quickly; an inflexible one takes hours or never arrives.

This is the measured respiratory exchange ratio divided by the meal's food quotient (the theoretical RER if the meal were fully oxidized as ingested). A ratio of 1.0 means whole-body substrate oxidation has fully matched the macronutrient composition of what was just eaten; <1.0 means oxidation is lagging behind intake (fat-dominant fuel selection persisting after a mixed or high-carb meal); >1.0 means net lipogenesis or carryover carb oxidation. The FQ of the high-fat test meal will be used.

This represents the drop from a reference RER (typically pre-meal fasting baseline, sometimes overnight minimum) to the lowest RER value observed. In a high-fat meal challenge this captures the magnitude of the fat-oxidation excursion: how far down the RER pushes when the meal is fat-dominant.

This represents the rate of RER change in the early postprandial window, usually fit as a linear slope over the first 30-90 minutes after ingestion. A steep slope would mean a rapid switch (metabolically flexible) and a shallow slope would indicate impaired metabolic flexibility.

This represents the amount of minutes from high-fat meal meal ingestion until RER reaches its lowest value. Pairing this will the change in RER nadir helps describe the fat oxidation excursion. That is, nadir magnitude expresses how much fat oxidation increased, whereas time-to-nadir exhibits how long it took to get there.

Skeletal muscle mass will be measured using D3-creatine dilution. Participants will be administered a 60 mg capsule with D3-creatine during Visit 1. Spot urine specimens will be collected between 120 hours (5 days) and 144 hours (6 days) after administration of the D3-creatine dose.

Fat-free mass will be quantified by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.

Fat mass will be estimated by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.

Body fat percentage will be estimated by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.

At Visit 1, a blood sample of 3 ml will be collected before ingesting an appropriate amount of sodium bromide based on body weight diluted in deionized water. A blood sample of 3 ml will be collected 4 hours after ingestion. During the 4-hour period participants must refrain from eating anything, but they can drink water if needed.

Total body water will be determined via two bioelectrical impedance devices (InBody S10 and ImpediMed SFB7) and deuterium dilution.