Anti-inflammatory Effects of Fiber

To Study the Effect of High Fat High Carbohydrate Meal on Oxidative Load, Inflammatory Mediators and Insulin Resistance in Normal and Obese Subjects

The main objective of this research is to investigate the effect of addition of fiber on the high fat high carbohydrate (HFHC) meal induced inflammation and oxidative stress mechanisms at the molecular level in humans, in vivo. The investigators have previously shown that the intake of one HFHC meal leads to an increase in oxidative stress and inflammation. HFHC meal also induces an increase in the expression of suppressor of cytokine signaling- 3 (SOCS-3) in the mononuclear cells (MNC), which interferes with insulin signal transduction and contributes to the pathogenesis of insulin resistance. In contrast, an American heart association (AHA) meal rich in fruits and fiber does not induce these effects. These observations are important since HFHC meal not only induces oxidative stress and inflammation but also lays the foundations of a potentially greater insulin resistance through the induction of SOCS-3, TLR-4 and TLR-2.

Study Overview

• Status: Completed
• Conditions: Postprandial Inflammation
• Intervention / Treatment: Other: HFHC meal; Dietary supplement: HFHC MEAL plus Fiber

Detailed Description

The main objective of this research is to investigate the effect of high fat high carbohydrate (HFHC) meal on inflammatory mechanisms at the molecular level in humans, in vivo versus HFHC meal plus fiber. HFHC meal includes egg muffin, sausage muffin sandwiches and two hash browns. The Investigators have previously shown that the intake of one HFHC meal leads to an increase in reactive oxygen species (ROS) generation and the expression of p47, the key subunit of NADPH oxidase, with a concomitant increase in intranuclear nuclear factor κB (NFkB) binding. More recently, the investigators have also shown that HFHC meal leads to an increase in plasma endotoxin (lipopolysaccharide, LPS) concentrations along with an increase in the expression of Toll like receptor-4 (TLR-4), the receptor for endotoxin, and TLR-2, the receptor for several products of Gram positive bacteria. In addition, it also causes an increase in lipopolysaccharide binding protein (LBP), the protein which facilitates the binding of LPS to CD14 and TLR-4. Finally, HFHC meal also induces an increase in the expression of suppressor of cytokine signaling- 3 (SOCS-3) in the mononuclear cells (MNC) (1), which interferes with insulin signal transduction and contributes to the pathogenesis of insulin resistance. In contrast, an AHA meal does not induce these effects. These observations are important since HFHC meal not only induces oxidative stress and inflammation but also lays the foundations of (2) a potentially greater response to an inflammatory challenge through the induction of an increase in LPS concentrations and the expression of TLR-4 and TLR-2; and (3) insulin resistance through the induction of SOCS-3, TLR-4 and TLR-2.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14215
      • ECMC Ambulatory Center, 3rd Floor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18 to 80 years of age
• Subject will be available for duration of the study and willing to comply with all study requirements
• Written and informed consent signed and dated
• Nonsmoker

Exclusion Criteria:

• Coronary artery disease (CAD): documented by history of myocardial infarction, angioplasty/stent placement, angina, exercise EKG positive for ischemia or angiographic evidence of CAD
• Patient on non-steroidal anti-inflammatory drugs or steroids
• Hepatic disease (transaminase > 3 times normal)
• Renal impairment (serum creatinine > 1.5 mg/dl)
• History of drug or alcohol abuse
• Participation in any other concurrent clinical trials
• Use of an investigational agent or therapeutic regimen within 30 days of study
• Pregnancy
• Premenopausal women who are trying to be pregnant
• Anemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: High fat high carbohydrate (HFHC) meal; Subjects will consume a HFHC meal. HFHC meal includes egg muffin and sausage muffin sandwiches and two hash browns which contain 88g carbohydrates, 51 g fat (33% saturated) and 34 g protein (carbohydrates 41%, protein 17%, and fat 42%). 35 ml of blood will be obtained at 1h ,2h,3h and 4 h and 5 ml at 15 min,30 min,45 min,75 min and 90 min . A total of 165 ml (11 tablespoon) blood will be collected.	Other: HFHC meal; 900 Cal high fat high carbohydrate fast food meal (HFHC). meal includes egg muffin and sausage muffin sandwiches and two hash browns which contain 88g carbohydrates, 51 g fat (33% saturated) and 34 g protein (carbohydrates 41%, protein 17%, and fat 42%).
Experimental: HFHC meal plus Fiber; HFHC meal includes egg muffin and sausage muffin sandwiches and two hash browns which contain 88g carbohydrates, 51 g fat (33% saturated) and 34 g protein (carbohydrates 41%, protein 17%, and fat 42%). Subjects will also receive FiberOne Original cereal 14 grams (half cup) before and after the HFHC meal. 35 ml of blood will be obtained at 1h ,2h,3h and 4 h and 5 ml at 15 min,30 min,45 min,75 min and 90 min . A total of 165 ml (11 tablespoon) blood will be collected.	Dietary supplement: HFHC MEAL plus Fiber; 900 Cal high fat high carbohydrate fast food meal containing egg muffin and sausage muffin sandwiches and two hash browns which contain 88g carbohydrates, 51 g fat (33% saturated) and 34 g protein (carbohydrates 41%, protein 17%, and fat 42%).with FiberOne Original cereal 14 grams (half cup) each before and after the HFHC meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of addition of fiber on the relative change of NF-Kappa B	The investigators hypothesize that addition of fiber intake will suppress NF-kappa B after HFHC meal. Therefore, changes in NF-kappa B activity will be compared as percent change form baseline after HFHC meal with or without fiber in lean and obese subjects	Baseline and 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of addition of fiber on Changes in ROS generation.	Changes in Reactive oxygen species (ROS) generation between the 2 visits (HFHC meal with or without fiber) will be compared as percent change from baseline.	Baseline and 1 week
effect of addition of fiber on Changes in TLR-4 mRNA expression in MNC	Changes in TLR-4 mRNA expression in MNC between the 2 visits (HFHC meal with or without fiber) will be compared as percent change from baseline.	Baseline and 1 week
effect of addition of fiber on Changes in SOCS-3 mRNA expression in MNC	Changes in SOCS-3 mRNA expression in MNC between the 2 visits (HFHC meal with or without fiber) will be compared as percent change from baseline.	Baseline and 1 week
effect of addition of fiber on Changes in insulin secretion between the 2 visits (HFHC meal with or without fiber) will be compared as percent change from baseline.	Changes in insulin concentrations between the 2 visits (HFHC meal with or without fiber) will be compared as percent change from baseline.	Baseline and 1 week

Collaborators and Investigators

• Sponsor: University at Buffalo

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimate): May 24, 2016

Study Record Updates

• Last Update Posted (Estimate): May 25, 2016
• Last Update Submitted That Met QC Criteria: May 23, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Fiber; inflammation; high fat diet; insulinogenesis
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 1955