Metabolically Abnormal Obesity, Metabolically Normal Obesity, Metabolic Syndrome, Non-alcoholic Fatty Liver Disease, Obesity
Conditions
Keywords
NAFLD, Obesity, Metabolic syndrome
Brief summary
The purpose of this study is to learn more about how the body stores fat in and around organs (for example in the liver) and why this affects some people's health more than others. Understanding this may lead to better treatments for diseases such as diabetes and cardiovascular disease.
Detailed description
The purpose of this study is to determine the specific cellular and organ system metabolic and immunologic alterations that are associated with insulin resistance and inflammation in order to identify putative mechanisms and novel bio-markers involved in the pathogenesis and progression of inflammatory and cardiometabolic diseases.
Interventions
OTHERWeight loss
Bariatric surgery-induced weight loss to achieve \ 20%-30% reduction in initial body weight
Sponsors
Pfizer
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
Lean, metabolically healthy group - Body mass index (BMI) 18.5-24.9 kg/m2, HbA1C ≤5.6%, fasting plasma glucose concentration \<100 mg/dl, 2-h OGTT plasma glucose concentration \<140 mg/dl and intrahepatic triglyceride (IHTG) content ≤5%. Obese, metabolically healthy group - BMI ≥30 kg/m2, HHbA1C ≤5.6%, fasting plasma glucose concentration \<100 mg/dl, 2-h OGTT plasma glucose concentration \<140 mg/dl and intrahepatic triglyceride (IHTG) content ≤5%. Obese, metabolically healthy group - BMI ≥30 kg/m2, IHTG content ≥5.6% and HbA1C ≥5.7% or fasting plasma glucose concentration ≥100 mg/dl or 2-h OGTT plasma glucose concentration ≥140 mg/dl. Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery - BMI 18.5-24.9 kg/m2, HbA1C ≤5.6%, fasting plasma glucose concentration \<100 mg/dl, 2-h OGTT plasma glucose concentration \<140 mg/dl and IHTG content ≤5%. Obese, scheduled for bariatric and gallbladder surgery - BMI ≥35.0kg/m2
Exclusion criteria
* active or previous history of liver diseases other than NAFLD * history of alcohol abuse * currently consuming ≥20 g alcohol/day * severe hypertriglyceridemia (\>300 mg/dL) * smoke tobacco * cancer diagnosis within the previous 5 years * medications that might confound the study results * pregnancy or lactation * exercise \>2 h/week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | Baseline | Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interleukin-6 (IL-6) | Baseline | Interleukin-6 is a marker of inflammation |
| Liver tissue inflammation | Baseline | Liver immune cell content |
| Abdominal adipose tissue inflammation | Baseline only in participants scheduled for bariatric surgery | Subcutaneous, omental and transverse mesocolic adipose tissue |
| TNF-alpha | Baseline | TNF-alpha is a marker of inflammation |
| Exosome-mediated intercellular signaling | Baseline only in participants scheduled for bariatric surgery | Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous, omental and transverse mesocolic adipose tissue and liver. |
| Change in exosome-mediated intercellular signaling | Before and after 20-30% weight loss (~3-4 months) in participants scheduled for bariatric surgery | Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue |
| Hepatic PNPLA3 synthesis rate | Baseline only in people scheduled for gallbladder or bariatric surgery | Synthesis rates assessed by stable isotope techniques in the fasted vs the fed states |
| Upper vs lower adipose tissue inflammation | Baseline (All groups) | Immune cell content in abdominal and femoral subcutaneous adipose tissue |
Countries
United States
Outcome results
None listed