Body Composition and Lipid Metabolism at Rest and During Exercise: A Cross-Sectional Analysis.

Study Overview
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Brief Summary
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The ability to upregulate fat oxidation at appropriate times such as during fasting, low to moderate intensity exercise and after a high fat meal, is popularly advocated. This is presumably due to the perception that a high capacity to utilise fat may improve (ultra) endurance performance and help in the regulation of body fat and metabolic diseases. In accordance, impaired fat use at rest has been associated with obesity and insulin resistance (Kelley et al., 1999). However, there is inconclusive and / or a lack of systematic evidence, especially in a large diverse range of adults, exploring: 1) Whether whole body fat use during exercise is altered in individuals with overweight or obesity compared to lean individuals 3) The intra-individual variability in whole-body fat use at rest and during exercise 4) Physiological, metabolic, lifestyle and genetic characteristics that are associated with whole-body fat use at rest and during exercise Therefore, the objectives of this study are three-fold: To explore whether whole body fat use is associated with body composition To explore associations between whole-body fat use and physiological, metabolic, lifestyle and genetic variables To assess the intra-individual variability of whole-body fat use. This study is an observational, exploratory cross-sectional study. A wide range of 'healthy' and 'at-risk of metabolic disease' adults will be recruited. Participants will be asked to visit a laboratory at the University of Bath four times. Visit 1 is a screening and study familiarisation visit. Visits 2 and 3 are to be completed within 7-14 days and involve lifestyle monitoring (dietary and physical activity), a one-off urine and blood sample, assessment of fuel use at rest and during exercise (the latter through an incremental graded cycling exercise test to exhaustion). Visit 4 is to assess body composition via a dual-energy x-ray absorptiometry (DEXA) scan in addition to an optional skeletal muscle and / or fat tissue biopsy.

Detailed Description
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Metabolic flexibility broadly refers to the ability to utilize the right fuel source for energy (primarily either carbohydrate or fat) at the right time (Kelley and Mandarino, 2000). This was first conceptualised at the level of skeletal muscle (Kelley and Mandarino, 1990; Andres et al., 1956). A main tenant originally captured by 'metabolic flexibility' is the predominant utilization of fat as an energy source under rested post-absorptive conditions in 'healthy' individuals (Kelley et al., 1999; Kelley and Mandarino, 1990). Recently, there has been a call to extend the concept of 'metabolic flexibility' to exercising conditions (Goodpaster and Sparks, 2017; Rynders et al., 2017). Similarly to at rest, fat provides an important source of energy during low-to-moderate intensity exercise (van Loon et al., 2001; Romijn et al., 1993). Thus, in healthy individuals at the whole-body and skeletal muscle level, it is robustly characterised and accepted that fat is an important and predominant fuel source for energy under such conditions. However, it is commonly proposed that a lower reliance upon fat as a fuel source is present in individuals with obesity and type 2 diabetes and consequently, has been implicated in the pathogenesis of such conditions (Rynders et al., 2017; Kelley and Mandarino, 2000). Alternatively, a high capacity to utilize fat under the aforementioned two situations is advocated to be a desirable trait for both athletes and non-athletes, presumably due to the perception that high rates of fat utilization may improve endurance performance and/or assist with the regulation of body fat and metabolic health. As such, much interest has been generated into upregulating fat utilization at appropriate times e.g. during fasting and low-to-moderate intensity exercise. Correspondingly, lower resting and exercising fat use has been reported in individuals with obesity vs lean (e.g. Lanzi et al., 2014; Perez-Martin et al., 2001; Kelley et al., 1999). Furthermore, greater fat use at rest has been associated with lower future body weight and fat gain / regain (e.g. Shook et al., 2016; Seidell et al., 1992), and during exercise with reduced short term post-exercise energy intake / balance (e.g. Hopkins et al., 2012), exercise-induced fat loss (Barwell et al., 2008) and weight loss / maintenance (Dandadell et al., 2017). Importantly, however, this relationship is not always apparent with similar (e.g. Blaize et a., 2014; Croci et al., 2014) or higher (e.g. Ara et al., 2011; Goodpaster et al., 2002; Horowtiz et al., 2000) rates of fat use at rest and during exercise reported in individuals with obesity compared to lean counterparts. Furthermore, cross-sectional and prospective associations do not always exist between lower fat use and greater body weight / fat mass gain or regain (e.g. Dandanell et al., 2017; Ellis et al., 2010). Thus, despite being popularly advocated, it is currently unclear whether lower fat use at rest or during exercise predisposes or is a characteristic of excess adiposity (i.e. obesity). The inconsistent findings could partly be due to numerous methodological discrepancies between studies such as participant characteristics, matching of comparative groups, the exercise protocol utilised and / or the assessment of body composition, lipid oxidation and cardio-respiratory fitness levels. Therefore, through the use of well-established and respected techniques, we aim to comprehensively and systematically explore whether whole-body fat use at rest and during exercise is: Altered in individuals with overweight or obesity compared to lean individuals Further determinants / factors that may influence fat use The intra-individual variation in fat use which will help to more confidently determine the above objectives.

Official Title
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Body Composition and Lipid Metabolism at Rest and During Exercise: A Cross-Sectional Analysis.

Conditions
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Lipid Metabolism, Substrate Metabolism, Exercise

Intervention / Treatment
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* Behavioral: Study Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be between 18 - 65 years of age male or female body mass index between 18.9 - 35 kg/m2 be able and willing to give informed oral and written consent complete and meet the defined criteria of pre-study questionnaires and screens Exclusion Criteria: Currently have or have a previous history of metabolic, cardio-pulmonary or musculoskeletal disease BMI below 18.9 or above 35 kg/m2 Have plans to change lifestyle (diet and/or physical activity) during the study period ( 7 - 21 days) Unwillingness or unable to sufficiently meet study demands

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Male and Female Adults<br>Completion of Study Protocol | Behavioral: Study Protocol<br>* Participants will complete three study protocols 7 - 28 days apart which includes: 3 x main trial days (max. 150 mins) involving body composition analysis, indirect calorimetry, a blood sample, optional muscle and / or adipose tissue biopsies and a maximal cardiorespiratory fitness test. 2 x lifestyle monitoring periods (physical activity and diet) for the prior 7 days before each main trial day. Maintenance of habitual habits, dietary and physical activity behaviour patterns We are observing biological / health parameters in a group of individuals who will be assessed under resting and exercising conditions. The current study does not involve an intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal rate of whole-body fat oxidation (mg/kg FFM/min) | Fat free mass (FFM). Assessed during the incremental stage maximal cardio-respiratory fitness test | 7 - 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal rate of whole-body fat oxidation (g/min) | Non-adjusted rate. Assessed during the incremental stage maximal cardio-respiratory fitness test | 7-14 days | 
| FATmax (% of maximum oxygen consumption) | The exercise intensity that maximal rate of whole-body fat oxidation occurs at. Expressed as % of VO2peak). Assessed during the incremental stage maximal cardio-respiratory fitness test. | 7 - 14 days | 
| FATmax (% of Watt max) | The exercise intensity that maximal rate of whole-body fat oxidation occurs at. Expressed as % of Watt max). Assessed during the incremental stage maximal cardio-respiratory fitness test. | 7 - 14 days | 
| FATmax (% of Heart Rate max) | The exercise intensity that maximal rate of whole-body fat oxidation occurs at. expressed either as % of heart rate max). Assessed during the incremental stage maximal cardio-respiratory fitness test | 7 - 14 days | 
| Whole-body substrate oxidation rates (Carbohydrates and Lipid) during exercise | Assessed during the incremental stage maximal cardio-respiratory fitness test via indirect calorimetry of expired gas samples. | 7 - 14 days | 
| Whole-body substrate oxidation rates (Carbohydrates and Lipid) at rest | Assessed at rest through the participant lying in a semi-supine position via indirect calorimetry of expired gas samples. | 7 - 14 days | 
| Resting metabolic rate | Assessed at rest through the participant lying in a semi-supine position via indirect calorimetry of expired gas samples. | 7 - 14 days | 
| Cardiorespiratory fitness (VO2peak) | Assessed during the incremental stage maximal cardio-respiratory fitness test | 7 - 14 days | 
| Habitual Energy Intake | Participants will be asked to complete a self-weighed food and drink diary before each main trial day (Visit 2 and 3) so that average daily calorie and macronutrient intake can be calculated. The procedure will be explained by the CI. This diet monitoring period must include 3 week-days, at least one 1 weekend day and the immediate 48-hrs prior to the beginning of each main trial (Visit 2 and 3). Additionally, the prior 48-hrs before Visit 2 will be replicated before Visit 3. | 7 - 21 days | 
| Habitual Energy Expenditure / Physical Activity | Physical activity will be measured by accelerometry and heart-rate monitoring for 7 days before each main trial day (Visit 2 and 3). This procedure will be explained by the CI. ntake can be calculated. The participants physical activity levels for the immediate 48-hrs prior to the beginning of each main trial (Visit 2 and 3) will be asked to be replicated as closely as possible. | 7 - 21 days | 
| Menstrual Cycle (females only) | Assessed through a self-reported menstrual cycle questionnaire | 7 - 21 days | 
| Self-reported Physical Activity level | Assessed by the International Physical Activity Questionnaire (long form) | 7-21 days | 
| Fasting glucose concentration | Assessed via plasma sample extracted from the blood sample | 7-21 days | 
| Fasting lipid profiles (triglycerides / cholesterol) | Assessed via serum sample extracted from the blood sample | 7-21 days | 
| Fasting Adipose tissue derived hormone concentrations (leptin, adiponectin) | Assessed via plasma sample extracted from the blood sample | 7-21 days | 
| Fasting catecholamine concentrations (epinephrine and norepinephrine) | Assessed via plasma sample extracted from the blood sample | 7-21 days | 
| Fasting sex hormone concentrations (17 beta-estradiol, testosterone, progesterone) | Assessed via serum sample extracted from the blood sample | 7-21 days | 
| Fasting pancreatic derived hormone concentrations (insulin and glucagon) | Assessed via plasma sample extracted from the blood sample | 7-21 days | 
| Hydration Status (urine specific gravity) | Assessed via analysis of urine sample with a refractometer | 7-21 days | 
| Age | Assessed via a participant questionnaire | 7-21 days | 
| Sex | Assessed via a participant questionnaire | 7-21 days | 
| Ethnicity | Assessed via a participant questionnaire | 7-21 days | 
| Smoking Status | Assessed via a participant questionnaire | 7-21 days | 
| Medication / supplement use | Assessed via a participant questionnaire | 7-21 days | 
| Dietary pattern / requirements (e.g. vegetarian, vegan, Celiac disease) | Assessed via a participant questionnaire | 7-21 days | 
| Body Mass (kg) | Assessed via body weighing scales | 7-21 days | 
| Body Mass Index (kg/m2) | Assessed by dividing body weight in kg by height in metres squared. | 7-21 days | 
| Waist circumference (cm) | Assessed via use of an anthropometric tape measure | 7-21 days | 
| Hip Circumference (cm) | Assessed via use of an anthropometric tape measure | 7-21 days | 
| Body fat percentage | Assessed via a dual energy xray absorptiometry scan at Visit 4. | 1 day | 
| Body fat localisation | Assessed via a dual energy xray absorptiometry scan at Visit 4. | 1 day | 
| Lean body mass | Assessed via a dual energy xray absorptiometry scan at Visit 4. | 1 day | 
| Body fat percentage | Bioelectrical Impedance Analysis from the body weighing scales | 7-21 days | 
| Genotyping analysis | Genotyping analysis will be assessed through the extraction of the buffy coat layer from the blood sample | 7 - 21 days | 
| Skeletal Muscle sample (Optional) | The optional muscle sample will be obtained from the quadriceps muscle using the Bergstrom technique on Visit 4. | 1 day | 
| Adipose Tissue (Fat) sample (Optional) | The optional fat sample will be obtained from the subcutaneous abdominal region (5 cm laterally of the umbilicus) via the 'lipoaspiration' technique on Visit 4. | 1 day | 
| Fat mass index (body fat in kg/m2) | Assessed by dividing body fat in kg by height in metres squared. | 7 - 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maximal Fat Oxidation, Exercise, Intra-individual variability, Determinants, Whole-body fat oxidation, Body composition