Metabolically Healthy Obesity
Conditions
Keywords
Gut-vascular axis, Intestinal permeability, vascular function, obesity
Brief summary
The investigators seek to better understand how a single high-fat meal impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity" (obesity and largely normal cardiometabolic profile) and "metabolically healthy normal-weight individuals." Second, the investigators seek to understand how a prebiotic fiber (inulin) impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity."
Detailed description
This study consists of two parts (part 1 and part 2) that are approved under the same IRB approval code. As a result, there is only one unique identifier for the entirety of this project. As a results, the investigators have included both parts in this registration. Part 1 of project: The investigators will recruit individuals with a BMI in the normal (18.5-24.9 kg/m2) or obesity (\>30.0 kg/m2) ranges from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" and "metabolically healthy normal-weight" - our two groups of interest. Each participant will complete one meal trial. At the meal trial, an intravenous catheter will be inserted and baseline blood sample collected. Next, vascular assessments (i.e., flow mediated dilation \[FMD\], pulse wave analysis \[PWA\], pulse wave velocity \[PWV\]) will be completed. Then, participants will consume the high-fat meal consisting of heavy cream, chocolate syrup, and protein powder. The meal will contain \ 700 calories (55g fat). Following completion of the meal, blood samples will also be collected at 1-, 2-, 3-, 4-, 5-, and 6-hours. At each time point the investigators will collect serum to assess biomarkers of intestinal permeability and inflammation. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post high-fat meal and examine differences in gene and protein expression, as well as nitric oxide production. Additional blood will be collected for peripheral blood mononuclear cell isolation at baseline and 3 hours. Vascular assessments listed above will be repeated at 2-, 4-, and 6-hours. Participants will provide a stool sample collected at home for microbiome analyses. Part 2 of project: The investigators will recruit individuals with a BMI in the obesity (\>30.0 kg/m2) range from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" - our sole group of interest. Qualifying participants will report for a baseline assessment. At the baseline assessment, the investigators will collect fasting blood samples to assess biomarkers related to gut, immune, and vascular health. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post intervention and examine differences in gene and protein expression, as well as nitric oxide production. Next, vascular assessments (i.e., flow mediated dilation \[FMD\], pulse wave analysis \[PWA\], pulse wave velocity \[PWV\]) will be completed. This will conclude data collection and participants will be randomized to receive 6 weeks of supplemental inulin (a soluble fiber) or a placebo (maltodextrin). At 2-, 4-, and 6-weeks of the intervention, the same samples and measurements will be collected at in-lab visits. Stool samples will be collected at baseline and 6 weeks.
Interventions
DIETARY_SUPPLEMENTInulin Supplementation
Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).
DIETARY_SUPPLEMENTMaltodextrin (Placebo)
Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).
OTHERHigh-fat meal
All participants in part 1 (both metabolically healthy normal weight and metabolically healthy obesity) will consume a high-fat meal designed to invoke changes in gut, immune, and vascular parameters.
Sponsors
Ball State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Intervention model description
In part 1 of the study, all participants (n=20 with metabolically healthy obesity and n=20 with metabolically healthy normal weight) will consume a single high-fat meal. There is no randomization. In part 2 of the study, metabolically healthy obese individuals (n=30) will be randomized to consume supplemental inulin or maltodextrin (placebo) for 6 weeks. The present project is approved under one IRB application, so the investigators are unable to separate part 1 and part 2 into two CT.gov entries. The investigators have selected "randomized" below, but in reality there is no randomization procedures in part 1.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-55 years old. * BMI is 18.5-24.9 kg/m2 or \>30kg/m2 (part 1). BMI \> 30 kg/m2 (part 2) * Not pregnant or expecting to become pregnant (females only). * Not postmenopausal (females only). * Have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol"). * Have not been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes). * Have not been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease). * Do not regularly take anti-inflammatory drugs (more than 2x week) or are able to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit. * Have not taken antibiotics or probiotics in the last month. * Do not use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs. * Do not use weight-loss drugs (e.g., Ozempic, Wegovy). * Have not had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass). * Do not use tobacco products or any illicit drugs. * Do not have a pacemaker. * Do not have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies). * Able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)
Exclusion criteria
* Not 18-55 years old. * BMI is not 18.5-24.9 kg/m2 or \>30kg/m2 (part 1). BMI is not \> 30 kg/m2 (part 2) * Pregnant or expecting to become pregnant (females only). * Postmenopausal (females only). * Do not have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol"). * Have been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes). * Have been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease). * Regularly take anti-inflammatory drugs (more than 2x week) or are unable to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit. * Have taken antibiotics or probiotics in the last month. * Use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs. * Use weight-loss drugs (e.g., Ozempic, Wegovy). * Have had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass). * Use tobacco products or any illicit drugs. * Have a pacemaker. * Have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies). * Not able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum lipopolysaccharide binding protein | Through study completion, up to 2 years | Part 1: The investigators will measure lipopolysaccharide binding protein at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure lipopolysaccharide binding protein at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum interleukin-6 | Through study completion, up to 2 years. | Part 1: The investigators will measure interleukin-6 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure interleukin-6 at baseline and 2-, 4-, and 6-weeks post intervention. |
| Flow-mediated dilation | Through study completion, up to 2 years | Part 1: The investigators will measure flow-mediated dilation at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure flow-mediated dilation at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum C reactive protein | Through study completion, up to 2 years | Part 2: The investigators will measure C reactive protein at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum lipopolysaccharide | Through study completion, up to 2 years | Part 1: The investigators will measure lipopolysaccharide at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure lipopolysaccharide at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum TNF-alpha | Through study completion, up to 2 years | The investigators will measure serum TNF-alpha at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure TNF-alpha at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum zonulin | Through study completion, up to 2 years. | Part 2: The investigators will measure serum zonulin at baseline and 2-, 4-, and 6-weeks post intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Augmentation Index | Through study completion, up to 2 years | Part 1: The investigators will measure augmentation index at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure augmentation index at baseline and 2-, 4-, and 6-weeks post intervention. |
| Pulse-wave velocity | Through study completion, up to 2 years | Part 1: The investigators will measure pulse-wave velocity at baseline and 2-, 4-, 6-hours after the meal. Part 2: The investigators will measure pulse wave velocity at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum soluble CD14 | Through study completion, up to 2 years | Part 1: The investigators will measure serum soluble CD14 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure serum soluble sCD14 at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum IL-1 beta | Through study completion, up to 2 years | Part 1: The investigators will measure serum IL-1 beta at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. Part 2: The investigators will measure serum IL-1beta at baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum soluble VCAM-1 | Through study completion, up to 2 years | Part 1: The investigators will measure serum soluble VCAM-1 at baseline and , 1-, 2-, 3-, 4-, 5-, and 6-hours after the meal. |
| Peripheral blood mononuclear cell transcriptome | Through study completion, up to 2 years | Part 1: The investigators will measure interleukin-6 at baseline and 3-hours after the meal. |
| Serum treated HAEC transcriptome | Through study completion, up to 2 years | Part 1: The investigators will measure the HAEC transcriptome after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure the HAEC transcriptome after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention. |
| Serum treated HAEC eNOS and NFkB protein expression | Through study completion, up to 2 years | Part 1: The investigators will measure HAEC eNOS and NFkB protein expression after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure HAEC eNOS and NFkB protein expression after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention. |
| Microbiome composition (shotgun sequencing) | Through study completion, up to 2 years | Part 1: The investigators will determine microbiome composition once within one week of participants completing the meal trial. Part 2: The investigators will measure microbiome composition at baseline and 6-weeks post intervention. |
| Serum treated HAEC nitric oxide production | Through study completion, up to two years. | Part 1: The investigators will measure the HAEC nitric oxide production after treatment with baseline and 2-, 4-, 6-hour post-meal serum. Part 2: The investigators will measure HAEC nitric oxide production after treatment with serum from baseline and 2-, 4-, and 6-weeks post intervention. |
Countries
United States
Contacts
CONTACTBryant Keirns, PhD
PRINCIPAL_INVESTIGATORBryant Keirns, PhD
Ball State University
Outcome results
None listed