Energy Metabolism and Acute Effects of Protein Diets in Metabolically Obese Normal Weight Individuals

Asians tend to develop type 2 diabetes (T2D) at lower body mass index (BMI) levels and younger ages compared to other populations. This leads to a longer duration of suffering from long-term complications associated with the disease, ultimately resulting in shorter life expectancy. Notably, approximately 40% of newly diagnosed T2D cases in Asians occur in individuals considered lean, with a BMI reported to be less than 22 kg/m2. This phenomenon is termed the "Metabolically Obese Normal Weight" (MONW) phenotype. MONW individuals are characterized as having a normal body weight but exhibiting obesity-related metabolic disturbances, including excess body fat with ectopic fat deposition, insulin resistance, and dyslipidemia.

Asian populations have higher prevalence of abdominal obesity, accounting for \~60% of the global diabetic population. Type 2 diabetes (T2D) developing at lower BMI levels and younger ages compared to Western populations, suggest underlying metabolic issues in Asian. A cluster of metabolically obese, normal weight (MONW) individuals are identified in 40% of newly diagnosed Asian T2D.

MONW individuals have normal body weight but exhibit obesity-related metabolic disturbances, such as excess body fat, insulin resistance, and dyslipidemia, predisposing them to develop metabolic symptoms such as T2D and cardiovascular disease. They also show reduced physical activity, lower aerobic capacity, low muscle quality and impaired thermogenesis. Elevated plasma amino acids are associated with insulin resistance, resembling obesity, diabetes and sarcopenia. Given the complex nature of MONW, further examination is needed for early diagnosis and effective prevention strategies. Increased protein intake is known to improve satiety, thermogenesis and muscle health, while enhancing insulin sensitivity and fat oxidation. High-protein diets can aid in weight loss and are often preferred over traditional calorie restriction for combating obesity. In our previous study, a 5% weight loss from calorie restriction improved body composition and metabolism in MONW individuals. Hence, this study aims to 1) better understand the physiology and energy balance of MONW individuals; 2) identify biomarkers for early diagnosis; and 3) examine the effects of high-protein diets on the metabolism of MONW individuals. The study will involve participants of Chinese descent, evaluating metabolic biomarkers in energy balance and the impact of different protein sources on their acute metabolic effects.

Eligibility Criteria:
Inclusion Criteria:

* Body mass index between 18.5 - 24.9 kg/m2
* Non-diabetic
* Blood pressure (≤140/90 mmHg)
* \<5% weight change in the past 6 months
* Fasting triglyceride \< 90 mg/dl and HOMA-IR ≤ 1.0 will be defined as healthy subjects
* Fasting triglyceride ≥ 90 mg/dl and HOMA-IR \> 1.0 will be defined as MONW subjects

Exclusion Criteria:

* • Smoker or currently on nicotine therapy

  * Regularly consume alcohol \>1 unit per day
  * On hypocaloric/hypercaloric diet aiming for weight loss/gain
  * An athlete or sportive person with regular exercising \>3 times per week and \>45 minutes per section.
  * Currently receiving therapy (e.g. insulin) or any medication/ treatment (including supplements) that may affect glucose and lipid metabolism, energy metabolism or body composition
  * Currently on steroids, protease inhibitors, or antipsychotics therapies
  * Has symptomatic Irritable Bowel Syndrome
  * Has glucose-6-phosphate dehydrogenase (G6PD) deficiency
  * Had major medical or surgical event requiring hospitalization within the preceding 3 months
  * Participated in drug trials within 3 months before the start of the study
  * Donated blood within 3 months before the start of the study
  * Has intolerances or allergies to any of the study foods (eg. anaphylaxis to glutens)
  * Pregnant (pregnancy test will be done), lactating, or planning to be become pregnant during the study period
  * Has active Tuberculosis (TB) or currently receiving treatment for TB
  * Has chronic infection or is known to suffer from or has previously suffered from or is a carrier of Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV)
  * Has claustrophobia, trypanophobia, or hemophobia
  * Unwilling to consume study foods
  * Inadequate fluency in the English language
  * Unable to understand the study procedures and signs forms providing written informed consent to participate in the study.
  * Is a member of the research team or their immediate family members. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted