Role of Fasted Exercise on Improving Cardiometabolic Health

Investigating the Role of Fasted Exercise on Improving Cardiometabolic Health; a Potential Mediatory Role of Sirtuins

The aim of this randomised control trial is to investigate the role of fasted exercise on cardiometabolic health. Participants will be assigned to one of three conditions, fasted exercise, fed exercise and control (no exercise). Participants in the exercise groups will complete four weeks of moderate intensity cycling exercise, three times per week, either in the fasted or fed state according to their group assignment. Experimental trials involving anthropometric and cardiometabolic disease risk factor measurements as well as metabolic responses to a subsequent meal ingestion following exercise will be compared pre-intervention and post intervention.

The aim of this study is to investigate the effect of fasted exercise on cardiometabolic health and the potential mediatory role of sirtuins. The objectives are to investigate: The effect of a single bout of fasted exercise on acute metabolic responses following a high fat meal. The effect of four weeks of fasted exercise training on cardiovascular and metabolic disease risk factors. The effect of four weeks of fasted exercise training on circulating levels and subcutaneous adipose tissue gene expression of SIRT1, SIRT3 and SIRT6. A randomised control trial will be conducted with volunteers allocated under the conditions of a) no exercise (control), b) fasted exercise training (FASTEX) and c) fed exercise training (FEDEX). The pre- and post-intervention visits will consist of 50 minutes of cycling at a moderate exercise intensity for both the FASTEX and FEDEX groups. The control group would not perform any exercise. The FASTEX group will perform the exercise in the fasted state, whilst the FEDEX and control groups will be fed a standardised breakfast meal one hour in advance of the exercise period. Following the exercise period, the participants will be fed a high fat meal and metabolic responses to the meal will be measured for four hours. Multiple blood samples will be obtained as well as a sample of subcutaneous adipose (fat) tissue. The FASTEX and FEDEX groups will then complete four weeks of moderate intensity continuous exercise training, either fasted or fed according to their group, on three days per week whilst the control group will maintain their normal sedentary lifestyle. All participants will return to the laboratory for post-intervention testing at the end of the four weeks with the same protocols and measurements as the pre-intervention testing.

Cardiovascular disease, Diabetes Mellitus, Obesity, Cardiometabolic health, Exercise, Fasted, Sirtuins

12 blood samples collected at 0 (baseline), 75 (pre-exercise), 125 (immediately post-exercise), 155 min (pre-meal ingestion) then every 30 min after ingestion for four hours

Area under the circulating concentration versus time curve (AUC) of key metabolic markers following a high fat lunch meal

Fasted serum concentrations of clinical chemistry blood analytes (glucose, blood lipids, inflammatory markers)

Systolic and diastolic blood pressure and calculation of mean arterial pressure using systolic and diastolic values

17 measurements at 0 (baseline), 15 (post-breakfast meal period), 45 (30 min post-breakfast meal period), 75 (pre-exercise), every 10 min during exercise, 155 (pre-meal ingestion), then every 30 min for four hours.

Amount of time spent performing physical activity at different intensities (low, moderate, high) during the intervention period

Macronutrient (carbohydrate, fat, protein) composition of food intake using weighed food diary record during the intervention period

Inclusion Criteria: Male or female Non-smokers Physically inactive (partake in no more than one exercise session per week on average) Body mass index >18.5 kg/m2 Healthy as assessed by medical screening questionnaire Prior recipient of local anaesthetic with no known adverse effects, no known hypersensitivity or no other health issue that may constrain the administration of lidocaine hydrochloride Free from musculoskeletal injury and able to perform cycling exercise Capacity to give informed consent Exclusion Criteria: Regular exerciser BMI < 18.5 kg/m2 Pregnant Allergy or intolerances to test meal products/ingredients (such as wheat or dairy products). Recent major body weight change (+/- 3 kg in the past month) Known hypersensitivity to Lidocaine Hydrochloride Cardiovascular disease - complete heart block or hypovolaemia Adam's-Stokes Syndrome Wolff-Parkinson-White Syndrome Porphyria Epilepsy Myasthenia Gravis Other chronic medical condition or diagnosis including respiratory (eg asthma), endocrine, cardiovascular, neuromuscular disorders. Taking medications or receiving treatment that may constrain the administration of lidocaine or local anaesthesia.

Planned communication of group results at a scientific conference. Planned publication in a scientific peer reviewed journal. Participant level data is not expected to be available as this complies with the conditions of the ethical approval granted for this study.