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:

1. To explore whether whole body fat use is associated with body composition
2. To explore associations between whole-body fat use and physiological, metabolic, lifestyle and genetic variables
3. 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.

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:

1. Altered in individuals with overweight or obesity compared to lean individuals
2. Further determinants / factors that may influence fat use
3. The intra-individual variation in fat use which will help to more confidently determine the above objectives.

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

Adults