Effect of High Fat Diet on Muscle Metabolism
|ClinicalTrials.gov Identifier: NCT02328235|
Recruitment Status : Completed
First Posted : December 31, 2014
Last Update Posted : October 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Diabetes||Other: High Saturated Fat Diet||Not Applicable|
Objective: To discern the potential mechanism(s) by which high saturated fat feeding disrupts normal skeletal muscle metabolism. Our working hypothesis is that high saturated fat feeding increases gut permeability and blood endotoxin, which elicits pro-inflammatory signaling in skeletal muscle and alters the normal adaptive response to a meal. Preliminary evidence using a model of acute (5 days), high saturated fat feeding, isocaloric to habitual intake, in healthy, non-obese humans is presented herein to support this hypothesis.
Background: The inability for skeletal muscle to adapt fuel oxidation to fuel availability is termed metabolic inflexibility, a well characterized feature of disease states such as obesity, metabolic syndrome, and type 2 diabetes (T2D). The mechanism(s) responsible for skeletal muscle metabolic inflexibility are not known. Recently, there has been growing interest in the role of gut permeability and blood endotoxin in the pathology of metabolic derangements associated with obesity and T2D. Rodent studies have revealed direct links between the gut microbiome and metabolic disease, as well as associations between elevated blood endotoxin and metabolic dysregulation, both at the whole body and tissue level. High fat feeding in rodents is known to elicit elevated levels of blood endotoxin, a phenomenon that is termed metabolic endotoxemia. In humans, obesity and T2D are associated with increased blood endotoxin and single meals have been shown to elevate blood endotoxin, but to date, there is no evidence in humans that high fat feeding results in metabolic endotoxemia. Moreover, there are no established links between gut permeability, metabolic endotoxemia, and skeletal muscle metabolic function in humans.
Approach. We are proposing to utilize a model of acute high fat feeding in healthy humans to study the interplay between gut function, blood endotoxin, and skeletal muscle pro-inflammatory signaling and metabolic adaptability. We will employ a two-week lead-in period, during which research participants will be fed prepared meals that are isocaloric to their habitual diet, followed by five days of high saturated fat feeding. The high saturated fat feeding period will consist of prepared meals that are isocaloric to habitual diet with a macronutrient composition of 50% fat (45% of which will be saturated fat), 35% carbohydrate, and 15% protein. Studying healthy, nonobese humans in this context is an innovative approach on two levels: 1) any confounding influences associated with metabolic disease (obesity, diabetes, or metabolic syndrome) are eliminated, e.g., insulin resistance, hyperlipidemia, impaired gut function, pre-existing metabolic dysfunction and inflammatory tone; and 2) the isocaloric feeding design negates the confounding influence of a positive energy balance and allows us to specifically examine the effects of acutely increasing dietary saturated fat.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of High Fat Diet on Muscle Metabolism|
|Actual Study Start Date :||January 2013|
|Actual Primary Completion Date :||December 2017|
|Actual Study Completion Date :||March 9, 2018|
Experimental: High Saturated Fat Diet
Subjects will receive a high fat diet for 5 day following a 2 week lead in diet. Measurements will be made pre-post high fat diet
Other: High Saturated Fat Diet
Prior to the high fat diet and after baseline testing, subjects will be asked to eat a standard diet to "lead-in" to the high fat diet condition. The diet will contain 55% of calories as carbohydrate, 30% as fat, and 15% as protein. The high fat diet will contain 50-60% of calories as fat, 20-30% as carbohydrate, and 10-20% as protein. Subjects will be provided with all of their meals throughout the study.
- Metabolic Flexibility measured ex vivo in skeletal muscle using radio labeled carbon isotopes [ Time Frame: 1 day ]Assess substrate handling ex vivo in skeletal muscle using radio labeled isotopes pre and post high fat diet
- Intestinal Permeability using a 4 sugar probe test and mass spectrometry [ Time Frame: 24 hours ]Assess intestinal permeability with a variety of insoluble sugars and their level of excretion in the urine with mass spectrometry pre and post high fat diet
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02328235
|United States, Virginia|
|Virginia Polytechnic and State University|
|Blacksburg, Virginia, United States, 24061|
|Principal Investigator:||Kevin P Davy, PhD||Virginia Polytechnic Institute and State University|