Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber

Metabolic flexibility (METFLEX) is the ability to adapt fuel oxidation to fuel availability and energy demands. Impaired METFLEX is associated with weight gain, ectopic lipid deposition, insulin resistance, and the potential development of type 2 diabetes. Even if impaired METFLEX shows promise as an early predictor of future metabolic dysfunction, longitudinal studies have been lacking because of the absence of simple methods for assessing METFLEX. This project will further validate (reproducibility and comparison with hyperinsulinemic-euglycemic clamps) a novel approach for measuring METFLEX recently developed by the PI.

METFLEX is commonly measured during a hyperinsulinemic-euglycemic clamp. Yet, this technique is questioned because it relies on a non-physiological stimulus (intravenous glucose and insulin) and inherently suppresses fat oxidation via non physiological hyperinsulinemic conditions. In contrast, impaired fat oxidation in response to a high-fat meal is a more physiological indicator of metabolic inflexibility. The investigators have recently developed a method for measuring METFLEX by assessing the dynamics in respiratory exchange ratio (RER) in response to a high-fat standardized dinner in a whole-body room indirect calorimeter. Securing extramural funding for the aforementioned longitudinal studies employing this novel methodology is presently limited due to a lack of the following preliminary data: 1) quantification of the intra-subject variability of this novel METFLEX measure to perform power calculations (sample size) in large-scale prospective clinical trials, and 2) comparison of our method to a more accepted measurement of METFLEX. The overarching goal of this method development project is to generate reproducibility and validity data of The investigators' new assessment of METFLEX in a whole-body room indirect calorimeter against the METFLEX measured by a hyperinsulinemic-euglycemic clamp.

Inclusion criteria

• BMI between 18.5 kg/m^2 and 35 kg/m^2 (±0.5 kg/m^2 will be accepted)
• Willing to consume pre-prepared meals
• Non pregnant
• Bilateral oophorectomy or use of the following contraceptive methods (females only):

• monophasic oral contraceptives
• progesterone-only oral contraceptives
• injectable or implantable progesterone-only contraceptives

Exclusion criteria

• Unstable weight in the last 3 months [gain or loss >7 lb (or 3.2 kg)]
• Currently working shift work
• Smoking or use of tobacco products within the last 3 months
• History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
• Average screening blood pressure >140/90 mmHg
• Previous bariatric surgery (or other surgeries) for obesity or weight loss
• Use of medications affecting metabolism or sleep**
• History of cardiovascular disease, neurological disease, or other chronic diseases that affect sleep or metabolism
• Pregnant, planning to become pregnant, or breastfeeding
• Adherence to special restrained diets (e.g., low-carbohydrate, low-fat, or vegetarian/vegan diets) over the last 3 months.

• Sporadic use of these medications is acceptable (however, enrollment will be evaluated on a case-by-case basis). If taking sporadically, participants should not be taking the medication for 1-month prior to the first visit.

NOTE: Participants may also be excluded if deemed medically necessary by study Medical Investigator.