Precision Nutrition and Metabolic Function

The purposes of this study are: 1) to determine the mechanisms responsible for the development of cardiometabolic complications in some, but not all people with obesity; 2) determine the best dietary approach for cardiometabolic health; and 3) understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.

Excess adiposity causes alterations in metabolic function including impaired glucose homeostasis and insulin resistance, which are important risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). Not all people with obesity experience the typical metabolic complications associated with obesity. Approximately 25% of people with obesity are protected from the adverse metabolic effects of excess fat accumulation and are considered to be metabolically healthy based on their normal response to insulin. The mechanism(s) responsible for the differences in metabolic function among people with obesity is not known, but is likely to be multifactorial including dietary intake. The risk for developing T2D and CVD is also well known to increase with age, however, not all people that are metabolically healthy convert to a metabolically unhealthy phenotype over time. The mechanisms responsible for the stability of health status in some, but not all adults, are unclear. The overall goals of this study are to: i) determine the mechanisms responsible for the development of cardiometabolic complications in participants who will be carefully characterized into 3 distinct groups \[metabolically normal lean, metabolically normal obese and metabolically abnormal obese\], ii) to determine the optimal dietary approach for cardiometabolic health independent of weight change in people with metabolically abnormal obesity, and iii) perform a comprehensive longitudinal assessment of cardiometabolic health to understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.

Eligibility Criteria:
Inclusion Criteria:

* Metabolically healthy lean subjects must have a body mass index (BMI) 18.5-24.9 kg/m2, intrahepatic triglyceride (IHTG) content ≤5%, serum triglyceride (TG) concentration \<150 mg/dl, fasting plasma glucose concentration \<100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
* Metabolically healthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content ≤5%, serum TG concentration \<150 mg/dl, fasting plasma glucose concentration \<100 mg/dl, 2-hr OGTT plasma glucose concentration ≤140 mg/dl, and HbA1C ≤5.6%.
* Metabolically unhealthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content ≥5.6% and fasting plasma glucose concentration ≥100 mg/dl or 2-hr OGTT plasma glucose concentration ≥140 mg/dl or HbA1C ≥5.7%.

Exclusion Criteria:

* medical, surgical, or biological menopause;
* previous bariatric surgery where the gastrointestinal tract is reconstructed such as Roux-en-Y, sleeve gastrectomy and biliopancreatic diversion surgeries;
* laparoscopic adjustable gastric band (lab band) surgery within the last 3 years;
* structured exercise ≥250 min per week (e.g., brisk walking);
* unstable weight (\>4% change during the last 2 months before entering the study);
* significant organ system dysfunction (e.g., diabetes requiring medications, severe pulmonary, kidney or cardiovascular disease);
* cancer or cancer that has been in remission for \<5 years;
* polycystic ovary syndrome;
* major psychiatric illness;
* conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders);
* severe anemia;
* regular use of tobacco products;
* excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women);
* use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study;
* use of antibiotics in last 60 days;
* pregnant or lactating women;
* vegans, vegetarians, those with lactose intolerance and/or severe aversions/sensitivities to eggs, fish, nuts, wheat and soy, and/or any individuals with food allergies that induce an anaphylactic response;
* persons who are not able to grant voluntary informed consent