The goal of this pilot study is to understand the combined effects of fish oil and exercise in obesity-associated inflammation acutely. The investigators hypothesize that fish oil will improve gut bacteria profiles, which will in turn potentiate the benefits of an exercise program and reduce inflammation and metabolic risk.
Incidence of obesity continues to increase in the United States and worldwide, making its prevention or reduction a public health priority. Nutrition research that can lead to effective prevention strategies is greatly needed. Inflammation is a major underlying cause for obesity, and it is imperative that we understand how anti-inflammatory food sources, such as fish oil, could aid in reducing obesity. Moreover, exercise is effective at reducing systemic inflammation and improving insulin resistance. Both exercise and diet can influence health through changes in the gut microbiome; however, no studies have investigated how together these affect gut microbiome and overall metabolic health. The goal is to understand the combined effects of fish oil and exercise in obesity-associated inflammation. The investigators hypothesize that fish oil will improve gut bacteria profiles, which will in turn potentiate the benefits of an exercise program reduce inflammation and metabolic risk. This study will provide the foundation for development of novel strategies for obesity, inflammation, dyslipidemia and dysglycemia. Aim 1: Determine combined effects of n-3 PUFA and HIIT on improving metabolic risk: The investigators will test the hypothesis that n-3 PUFA in addition to HIIT will have beneficial effects on obesity-related markers of inflammation, dyslipidemia and insulin resistance in placebo, n-3 or exercise alone, and combined n-3 and exercise. Aim 1.1: Investigate the influence of n-3 PUFA and HIIT on body weight and composition: At baseline (week 0), anthropometric assessments will be performed, including: (1) height (m); (2) weight (kg); (3) waist circumference (cm); (4) hip circumference (cm); and body composition which will be assessed utilizing dual-energy X-ray absorptiometry (DXA) scanning. Anthropometric measures will be repeated at post-intervention (week 6). Aim 1.2: Investigate the influence of n-3 PUFA and HIIT on serum markers associated with obesity Fasting blood samples collected at weeks 1 and 6 will be analyzed for (1) markers of inflammation, including high sensitivity C-reactive protein (hs-CRP), IL-6, IL-10, MCP-1, and TNF-α; (2) adipokines, including adiponectin, resistin, and leptin; and (3) indices of systemic insulin resistance, including insulin and fasting blood glucose and (4) indices of dyslipidemia, including total cholesterol, high-density, lipoprotein (HDL), non-HDL, low- and very low-density lipoproteins (LDL and VLDL), total/HDL cholesterol, and triglycerides (TG) utilizing ELISA kits or Luminex analyzer \[1\] in the Nutrition, Exercise, \& Translational (NExT) Medicine Lab in the Department of Kinesiology \& Sport Management, TTU, Lubbock. Aim 2: Determine combined effects of n-3 PUFA and HIIT on improving gut dysbiosis: The investigators will test the hypothesis that n-3 PUFA supplementation will improve gut microbiota composition and related metabolites, which will result in reduced inflammation and ameliorate the metabolic response to a HIIT exercise intervention in an overweight population. This will be accomplished by identifying alterations in gut microbiota profiles following n-3 supplementation, HIIT or the interactive effects of both HIIT and n-3 PUFA. Aim 2.1: Investigate the influence of n-3 PUFA and exercise on gut microbiota composition Fecal samples will be collected by participants at their convenience in their homes and less than 24 hours prior to visiting the lab. Samples will be brought to the lab at weeks 1 and 6. Samples will be collected at home with investigator prepared kits and will be stored at -80°C until DNA extraction. Metagenomics analyses will be conducted in consultation with our collaborators at the University of Houston. Aim 2.2: Investigate the influence of n-3 PUFA and exercise on microbiota produced metabolites Fecal and serum short-chain fatty acid (SCFA)s, including acetate, propionate and butyrate, will be measured as markers of the above gut bacteria changes and in association with changes in serum markers of inflammation, dyslipidemia and dysglycemia. Fecal and serum SCFAs will be measured utilizing gas chromatography. Analyses will be conducted on fasting blood samples collected at baseline and post-intervention. Participants will be randomly allocated to 1 of 4 treatment groups (n = 120), each balanced for sex, BMI, lipid profile, and dietary intake. 1. placebo (safflower oil, AlaskOmega®) + flexibility (exercise control) 2. n-3 PUFA (4 grams, 3000 mg EPA and 1000 mg DHA, AlaskOmega®) + flexibility training (exercise control) 3. placebo (safflower oil, AlaskOmega®) + HIIT 4. n-3 PUFA + HIIT The goal is to conduct the study in smaller cohorts, such as 10-15 participants/group (n = 40-60). 4 grams n-3 PUFA (AlaskOmega®) per day (3000 mg EPA and 1000 mg DHA) will be taken by participants in n-3 PUFA groups for 6 weeks Placebo (safflower oil, AlaskOmega®, from Organic Technologies Inc.) will be taken by participants in placebo groups for 6 weeks A 4 x 4 HIIT exercise (4 intervals for 4 min at 85-95% HRmax with 3min active recovery at 50-70% HRmax) program, 3 days/week, conducted under virtual investigator supervision and utilizing cycle ergometers (Keiser M3i Indoor Bike) equipment in collaboration with the TTU Department of Kinesiology \& Sport Management for 6 weeks. If not asked to exercise, participants will be instructed to maintain their normal level of physical activity but will participate in time-matched control consisting of flexibility training led by investigators for 6 weeks. All participants will wear a heart rate monitor (Polar H10) provided by TTU throughout the training (HIIT and control) to monitor exertion level. Capsules will be administered in a double-blind fashion and will be identical in appearance. To ensure compliance, subjects will be reminded via phone (text message or phone call based on participant preference) to take their capsules and counts will be conducted when they come in for study visits. At the end of the 6-week study, assessments will be repeated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
4 grams n-3 PUFA (AlaskOmega®) per day (3000 mg EPA and 1000 mg DHA).
4 grams safflower oil (AlaskOmega®) per day.
A 4 x 4 high-intensity interval training (HIIT) exercise program 3 days/week for 6 weeks. This will include a 3 min warm up at 15% watt max followed by 4 intervals for 4 min at 65% watt max with 3 min active recovery at 15% watt max.
Mean Change from Baseline in Serum high-sensitivity C-reactive protein at 6 weeks
Serum high-sensitivity C-reactive protein (hs-CRP; mg/L)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Interleukin (IL)-6 at 6 weeks
Interleukin (IL)-6 (pg/mL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Interleukin (IL)-10 at 6 weeks
Interleukin (IL)-10 (pg/mL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Monocyte chemoattractant protein-1 at 6 weeks
Monocyte chemoattractant protein-1 (MCP-1; pg/mL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Tumor necrosis factor at 6 weeks
Tumor necrosis factor (TNF)-alpha (pg/mL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in High-density lipoprotein (HDL) at 6 weeks
High-density lipoprotein (HDL) (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Non-high-density lipoprotein (Non-HDL) at 6 weeks
Non-high-density lipoprotein (Non-HDL) (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Low-density lipoprotein (LDL) at 6 weeks
Low-density lipoprotein (LDL) (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Very-low-density lipoprotein (VLDL) at 6 weeks
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30 min of stretching 3 days/week for 6 weeks
Very-low-density lipoprotein (VLDL) (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Triglycerides at 6 weeks
Triglycerides (mg/dL).
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Total/HDL cholesterol at 6 weeks
Total/HDL cholesterol (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Total cholesterol (mg/dL) at 6 weeks
Total cholesterol (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Insulin at 6 weeks
Insulin (μU/mL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Fasting blood glucose at 6 weeks
Fasting blood glucose (mg/dL)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Skeletal Muscle Mass Percentage at 6 weeks
Skeletal Muscle Mass Percentage (%SMM): The percent of the body that is composed of skeletal muscle. Like %BF, this number is relative to total mass.
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Total Body Fat Percentage at 6 weeks
Total Body Fat Percentage (%BF): The percent of the body that is composed of fat. This will change based on the amount of fat there is as well as the amount of lean mass there is.
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Cardio Respiratory Fitness at week 0
VO2 Max (mL/kg/min)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Bacterial Profile at 6 weeks
Fecal Microbial DNA (16s Sequencing)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Serum Acetate Profile at 6 weeks
Serum Acetate (SCFA: gas chromatography analysis)
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Propionate Profile at 6 weeks
Propionate (liquid chromatography tandem mass spectrometry (LC-MS/MS))
Time frame: Baseline and 6 weeks
Mean Change from Baseline in Butyrate Profile at 6 weeks
Butyrate (liquid chromatography tandem mass spectrometry (LC-MS/MS))
Time frame: Baseline and 6 weeks