Effects of Meal Macronutrients on Postprandial Lipids

Common inclusion criteria (all groups):

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Age >= 18 years
2. Average alcohol intake in the past 6 months \< 3 drinks (approximately 30g) per day (male) or \< 2 drinks (approximately 20 g) per day (female)

Healthy control specific inclusion criteria:

1. In good general health with no known active medical conditions as evidenced by medical history
2. Fasting glucose \<100 mg/dL
3. HbA1c \<5.7%
4. Fasting triglycerides \<150 mg/dL
5. ALT and AST within normal limits
6. BMI >=18.5 to \<25 kg/m\^2 (or \<23 kg/m\^2 in participants of Asian descent)
7. Not taking any medications or supplements that, in the opinion of the investigator, would interfere with interpretation of study data.

Metabolic syndrome specific inclusion criteria

1. Obesity defined as either

   1. BMI >30 kg/m\^2 (or >=27 kg/m\^2 in participants of Asian descent), OR

   2. Elevated waist circumference as defined below:

      • Country/Ethnic group - Europid, Sub-Saharan African, Eastern Mediterranean and Middle East (Arab):

        • Sex: Male; Waist circumference: >=94cm
        • Sex: Female; Waist circumference: >=80cm

      • Country/Ethnic group - South Asian, Chinese, Japanese, Ethnic South and Central American:

        • Sex: Male; Waist circumference: >=90cm
        • Sex: Female; Waist circumference: >=80cm

   Plus any 2 of the following

2. Elevated triglycerides defined as EITHER

   1. Fasting triglycerides >= 150 mg/dL at screening, OR
   2. Specific treatment for hypertriglyceridemia

3. Low HDL cholesterol, defined as EITHER

   1. HDL \<40 mg/dL (males) or \<50 mg/dL (females) at screening, OR
   2. Specific treatment for low HDL

4. Elevated blood pressure defined as EITHER

   1. Systolic BP >= 130 at screening, OR
   2. Diastolic BP >= 85 mm Hg at screening, OR
   3. Treatment of previously diagnosed hypertension

5. Elevated glucose defined as EITHER

   1. HbA1c >= 5.7% (at screening), OR
   2. Fasting serum glucose >= 100 mg/dL (at screening), OR
   3. 2-hour post-load glucose levels >= 140 mg/dL (by history), OR
   4. Prior diagnosis of type 2 diabetes

Lipodystrophy-specific inclusion criteria:

1. Clinical diagnosis of generalized or partial lipodystrophy based on reduction in adipose tissue outside the normal range in some or all adipose depots (including, at a minimum, the gluteofemoral depot).
2. Insulin resistance as defined by fasting insulin >22.5 or high exogenous insulin requirement (> 2 units per kg per day or > 200 units total per day) at screening.

Nephrotic syndrome specific inclusion criteria

1. History of biopsy proven non-diabetic glomerular disease (any histology)

2. Nephrotic range proteinuria defined by ANY of the following:

   1. Protein/creatinine ratio uPCR >= 3.5 g/g at screening, OR
   2. 24 hour protein excretion >= 3.5 gr/24hr) at screening, OR
   3. History of nephrotic range proteinuria (as defined above) within the past 5 years but in complete (defined as proteinuria \<= 0.3 g/day or partial remission (defined as a 50% or greater decrease in proteinuria compared to baseline and proteinuria \< 3.5 g/day) based on 24 hr urine or uPCR at time of screening

EXCLUSION CRITERIA:

Common exclusion criteria (all groups):

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Consuming extreme macronutrient diet (e.g., very low-carbohydrate, high fat diets such as ketogenic, "paleo" or Atkins diets, among others).
2. Plans to actively gain or lose weight during the study period (other than changes in water balance as clinically needed in subjects with nephrotic syndrome).
3. Change in body weight of >5% or >3 kg (whichever is larger) in the 3 months prior to screening (by participant report) in participants who do NOT have nephrotic syndrome.
4. Body weight >450 lbs (upper limit that can be accommodated by DXA scanner).
5. Participating in a regular strenuous exercise program (> 2h/week of vigorous activity) as determined by volunteer report or evidence of vigorous exercising in order to lose weight, change body shape, or to counteract the effects of eating.
6. Uncontrolled diabetes, defined as HbA1c >9% at screening.
7. Lipemia defined as fasting or non-fasting triglycerides of >1000 mg/dL at screening.
8. Renal dysfunction defined as eGFR \<50 mL/min/1.73 m\^2 at screening.

9. In participants with liver disease, history of decompensated advanced liver disease, defined as direct bilirubin > 0.5 g/dL, PT > 18 seconds, albumin \< 3 g/dL, MELD score > 12, or history of ascites, encephalopathy, variceal bleeding, spontaneous bacterial

   peritonitis or liver transplant.

10. History of hypertriglyceridemia-induced pancreatitis within 3 months prior to screening.
11. Positive pregnancy test or breastfeeding at screening.
12. Clinically significant abnormalities in thyroid function, blood counts, as assessed by screening labs.
13. Acute cardiovascular events within the past 6 months
14. Anemia (Hgb \<10 mg/dL in women or \<12 mg/dL in men) at screening
15. Food allergies or other dietary restrictions that could increase risk associated with test meals or cause the subject to be unwilling to consume test meals (i.e. celiac disease, vegan diets).
16. Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel motility problems, or other known conditions that could affect intestinal fat absorption.
17. Subjects treated with tamoxifen, estrogens, or progestins that have not been stable for >4 weeks prior to screening.
18. Blood donation in the last 2 weeks or planned blood donation during the study
19. Subjects requiring regular transfusions for any reason.
20. Subjects with known gastroparesis
21. Inability to adhere to Lifestyle Considerations throughout study duration.
22. Inability of the subject to understand and the unwillingness to sign a written informed consent document.
23. Unwillingness to comply with all study procedures and unavailable for the duration of the study
24. Any other condition or medication which, in the opinion of the investigator, increases risk to the subject, prevents the subject from complying with study procedures, prevents the subject from completing the study, or interferes with the interpretation of study results.