Impact of a High Saturated Fat Diet on Fasted Systemic and White Adipose Tissue Inflammatory Responses

Study Overview
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Brief Summary
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This study will investigate the effect of a 7-day westernised high-fat (65% of kilocalories), high-calorie (150% of requirements) diet on markers of inflammation in the blood and white adipose tissue. Participants will firstly complete a 3-day weight maintenance phase (Days 1-3) before completing a 7-day high fat diet intervention (Days 4-10). On days 4 and 11 participants will complete a laboratory visit where anthropometric measurements, blood and adipose samples will be collected. The investigators hypothesise that consuming a high-fat, high-calorie diet for 7 days will alter the inflammatory responses in white adipose tissue and will induce metabolic endotoxaemia / systemic inflammation.

Official Title
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Impact of Short-term Overfeeding With a Saturated Fat-rich Diet on Fasted Systemic and White Adipose Tissue Inflammatory Responses

Conditions
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Inflammation, Obesity, Inflammatory Response, Cardiovascular Diseases

Intervention / Treatment
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* Other: High Fat Diet


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 18-40 years BMI = 21.0-29.9 kg/m2 Male or female Physically active (> 3 x 30 min moderate exercise per week) Healthy No cardiometabolic (e.g. heart disease, high blood pressure, type 2 diabetes) or inflammatory illness Exclusion criteria: Inactive (< 3 x 30 min moderate exercise per week) Smoker Women who are pregnant or lactating Medication/supplements known to interfere with study outcomes or prescribed antibiotics within the last 3 months Unstable weight history (≥3kg loss or gain in the previous 3 months) An allergy to lidocaine Food allergies (e.g. gluten, dairy) and intolerances (e.g. lactose) which could impede compliance to the diet Vegetarian/ vegan (as the high-fat diet is based on animal fats) Consumption of probiotics yogurts during or within the four weeks prior to the start of the study (e.g. Actimel, Activia, Yakult, Yeo Valley) Alcohol consumption >28 units per week for a man (i.e. not more than 14 pints of beer or 28 small glasses of wine) or >21 units per week for a woman (i.e. more than 10 and a half pints of beer or 21 small glasses of wine) Any other unusual medical history or diet and lifestyle habits or practices that would preclude volunteers from participating in a dietary intervention or metabolic study Restrained eaters (determined by Three Factor Eating Questionnaire)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Fat Diet<br>Participants will consume a high-fat, high-calorie diet for 7 days (i.e. westernised diet) following a 3-day weight maintenance diet. Measurements will be made pre- and post-high fat diet intervention. | Other: High Fat Diet<br>* Participants will consume a high fat diet for 7 days with 65% of energy from fat. The diet will also provide an energy excess at 150% of energy requirements. Participants will be provided with all of their meals and snacks throughout the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein expression (content and phosphorylation) of key markers of metabolic inflammation in white adipose tissue (for example assessment of NFKB/IKBa total protein and phosphorylation by western blot analysis) | This will be assessed following the collection of fasted white adipose tissue samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Markers of Inflammation (for example CRP, TNFa and IL-6 concentrations, determined by spectrophotometric assay/ ELISA) | Assessed following the collection of fasted blood samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Gene expression of key markers of metabolic inflammation in white adipose tissue | This will be assessed following the collection of fasted white adipose tissue samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Fasting Serum Markers of Insulin Resistance (for example insulin and glucose concentrations, determined using an ELISA/ spectrophotometric assay) | Assessed following the collection of fasted blood samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Fasting Serum Lipid Profile (for example total, HDL and LDL cholesterol, TAG and NEFA concentrations, measured using a spectrophotometric assay) | Assessed following the collection of fasted blood samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Systemic Markers of Metabolic Endotoxemia (for example LBP and sCD14 concentrations, determined using an ELISA) | Assessed following the collection of fasted blood samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Immune Cell Populations in the Blood | Assessed following the collection of fasted blood samples | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Anthropometric Measurements (for example height and weight that will be aggregated to report BMI in kg/m^2) | Measured using standard equipment | Change between pre- and post-high fat diet (assessed on days 4 and 11) | 
| Physical Activity | Assessed using Actigraph accelerometers | Habitual physical activity will be assessed for 3 days prior to commencing the high-fat diet intervention (days 1-3) and during the final 3 days of the intervention (days 8-10) |