Lean and Obese: Dietary Inflammation

Study Overview
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Brief Summary
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In the Lean and Obese Dietary Inflammation (LODI) study, the primary goal is to determine the effect of short-term intake of high dietary fat (5 days) compared to low fat intake (5 days) in a cross-over design in older adults (men and women) with normal body weight or obesity. Inflammation will be examined by measuring serum endotoxin and other markers, as well as the fecal microbiota.

Detailed Description
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In the Lean and Obese Dietary Inflammation (LODI) study, short-term intake of a high-fat diet (HFD) that is also high in saturated fatty acids will be examined compared to a low-fat diet (LFD) in individuals who are normal body weight (BMI 19.5-24.9) or who have obesity (BMI of 30 - 40 kg/m2). To characterize persons at baseline, this study will examine body composition, and serum glucose, endotoxin, inflammation and intestinal permeability during fasting and in response to a mixed meal. Also, while it is known that long term intake of foods affects the microbiota, it is unclear whether short-term consumption of a HFD will shift towards a pro-inflammatory gut microbiota compared to a low fat intake. This will be tested in a cross-over design (5 days on a HFD, washout, and 5 days on a LFD) with order randomly assigned in older adults (50+ years of age) who have obesity or are normal weight, and will also be examined by estimated visceral adipose tissue level.

Official Title
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Dietary Inflammation in Older Adults: the Role of Obesity

Conditions
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Obesity, Inflammation, Dietary Fat

Intervention / Treatment
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* Other: Low Fat Diet (LFD)
* Other: High Fat Diet (HFD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or Women Age 50-79 years (only postmenopausal women > 2 years) Body mass index (20-25 kg/m2; and 30-40 kg/m2)* Exclusion Criteria: Diagnosed with, active, or history of liver cirrhosis, chronic or persisting hepatitis Diagnosed with, active, or history of cancer History of gastrointestinal disease or surgical procedure for weight loss. Diagnosed with immune diseases, type 2 diabetes, pancreatitis, or infectious diseases Any surgery in the past 6 months Currently using or have used antibiotics continuously > 3 days in the past 3 months Regular use of medications for that affect the gastrointestinal tract, cholecystitis, urinary tract infection, severe organic diseases including coronary heart disease, myocardial infarction, infectious diseases including pulmonary tuberculosis and AIDS Known allergy or intolerance to any ingredients in the dietary intervention program Alcohol or illicit drug abuse Current Smoker or have quit smoking in the past 3 months Recent colonoscopy (within the previous two months) Inability to follow any of the experimental diets (including low or high fat diet) or to perform the collections required for this study Participants will also be excluded if they have extreme dietary habits, extreme levels of physical or athletic activity, or by changes in body weight >5 lbs. during the last 6 months Uncontrolled hypertension or uncontrolled hyperlipidemia in abnormal ranges. Participation in another clinical research trial that may interfere with the results of this study. As needed, BMI (kg/m2) will be adjusted accordingly for Asian lean and obese definitions

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obese<br>BMI in Obesity range | Other: Low Fat Diet (LFD)<br>* Subjects will be asked to adhere to a low fat diet (assigned in random order) and be counseled by a dietitian using 5 days of sample menus, monitored online using a shared nutrient analysis program, and supplied with low fat foods to increase compliance<br>* Other names: low fat diet;Other: High Fat Diet (HFD)<br>* Subjects will be asked to adhere to a high fat diet that is rich in SFAs (assigned in random order) and be counseled by a dietitian using sample 5 days of menus, monitored online using a shared nutrient analysis program, and supplied with high fat foods to increase compliance<br>* Other names: high fat (high SFA) diet;|
| Experimental: Normal weight (lean)<br>Normal body weight | Other: Low Fat Diet (LFD)<br>* Subjects will be asked to adhere to a low fat diet (assigned in random order) and be counseled by a dietitian using 5 days of sample menus, monitored online using a shared nutrient analysis program, and supplied with low fat foods to increase compliance<br>* Other names: low fat diet;Other: High Fat Diet (HFD)<br>* Subjects will be asked to adhere to a high fat diet that is rich in SFAs (assigned in random order) and be counseled by a dietitian using sample 5 days of menus, monitored online using a shared nutrient analysis program, and supplied with high fat foods to increase compliance<br>* Other names: high fat (high SFA) diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endotoxin from Low to High fat diet | serum and stool | Change from LFD (5 days) to HFD (5 days) over an average of 6 weeks | 
| Change in Microbiome composition | stool | Change from LFD (5 days) to HFD (5 days) over an average of 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers | Serum IL6, hsCRP, lipopolysaccharide binding protein, toll like receptor 4 | Change from LFD (5 days) to HFD (5 days) over an average of 6 weeks | 
| Change in Zonulin | Serum zonulin | Change from LFD (5 days) to HFD (5 days) over an average of 6 weeks | 
| Endotoxin in response to a meal | Serum inflammatory response to a mixed meal tolerance test (MMT) (peak and AUC) | Change over 5 hour MMT | 
| Lipopolysaccharide binding protein (LBP) in response to a meal | Serum inflammatory response to a MMT (peak and AUC) | Change over 5 hour MMT | 
| Change in Triglycerides in response to a meal | Serum lipid response to a meal (peak and AUC) | Change over 5 hour MMT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, lean individuals, older adults, microbiome, dietary fat