A randomised controlled trial to evaluate the effects of marked weight loss combined with exercise training on metabolic, immunological, and imaging biomarkers of systemic and brain inflammation in participants undergoing bariatric surgery.

BARIATRIC SURGERY Eligible participants will undergo either gastric bypass or gastric sleeve surgery. Either surgery results in calorie restriction and significant weight loss (>20% of body weight). The safety and appropriateness of surgery for each candidate will have been determined by health staff. Following surgery, all participants will be reviewed frequently in the acute post-operative phase by health staff and should they become ineligible for the study, this will be communicated to the research team. Provided no complications, the research team will engage with participants during their routine 6-week follow-up to commence the exercise intervention. EXERCISE INTERVENTION: Between weeks 6 and 18, participants will attend a supervised physical activity programme. This programme will be individualised per each participant’s baseline activity and injuries. To measure baseline activity, all participants will wear a Fitbit physical activity tracker for seven continuous days (non-dominant wrist) and will complete a Physical Activity Readiness (PAR) questionnaire prior to their 6-week visit. At this visit, they will also complete a 6-minute walk test, VO2 sub-max test, and undergo a strength assessment with an accredited exercise physiologist (AEP) who will set up a personalised programme. The goal is for participants to work up to the below physical activity goals during the supervised period: (1) At least 150 minutes of moderate-intensity aerobic physical activity per week, 55-70% peak heart rate (monitored via Fitbit), 4-6 on Borg's modified Rating of Perceived Exertion (RPE) scale, involving large muscle groups, over 3 to 5 days per week. (2) Moderate-to-high intensity resistance exercises, 10-15 repetitions of each exercise, 4-6 on Borg's RPE scale, targeting large muscle groups, over 2 to 3 days per week. Aerobic All aerobic sessions will include a 3-minute light intensity warm-up and 2-minute cool down, equivalent to an RPE of 1-3 out of 10.. Aerobic exercises will be done via a treadmill, cycle ergometer, or land based walking as appropriate. Exercise intensity will be individualised from each participant’s percentage of their HRpeak or peak power output as measured during baseline testing. Aerobic exercise intensity will be monitored using the RPE scale and heart rate monitors, i.e., Fitbit. Resistance All strength sessions will be completed with a 5-minute cool down including static stretches and breathing. The resistance program will include 6 to 8 compound exercises focusing on major muscle groups to improve muscle strength and muscle mass such as squats, lunges, modified push-ups, etc. The dosage will include 1 to 3 sets of 8 to 15 repetitions performed at 55-70% of their 1 repetition maximum at baseline, with 1-2-minute rest between sets. The intensity and volume will progressively increase over the course of the 12-week program as tolerated. Technique will be closely monitored, and participants will be encouraged to perform the exercises with control. Participants will attend 2-3 1-hour appointments per week with their AEP. The supervised sessions will be delivered either in an individual setting or in a group of up to three, as needed. Following the supervised period, participants will be given an individualised home based programme and will be monitored via the Fitbit and regular phone follow-up. An option to attend one=to-one 1-hour virtual supervised sessions will be offered. These will be done via an agreed upon video conferencing software, e.g., Zoom or Microsoft Teams. If participants are not meeting exercising as per their programme, they will be contacted using the escalating methods of email, text message or phone calls and will be invited to attend in-person supervised sessions.