Fig. 1: Schematic overview of the study design.

After initial screening, healthy weight male participants underwent two baseline assessment days after an overnight fast at ~08:00. On the brain MRI testing day, diffusion-weighted imaging and CBF responses to 160 IU INI were acquired to investigate white matter integrity and brain insulin action (∆CBF = CBF MRI-2 − CBF MRI-1), respectively, followed by a reward-learning task. On a separate testing day (1–3 days apart), whole-body MRI for measurement of body fat mass and distribution and oGTTs for measurement of peripheral insulin sensitivity were performed. Afterwards, 18 participants were instructed to increase their daily caloric intake by 1,500 kcal for five consecutive days with high-caloric snacks. Eleven participants maintained their regular diet. Both testing days were repeated immediately after the 5-day HCD or regular diet period at follow-up 1. At follow-up 2, the brain MRI testing day was repeated 7 days after resuming a regular diet. Eating behaviour questionnaires were acquired during all testing days. Between visits, participants recorded their food intake and daily step activity. The timing of the follow-up visits was adapted to the first day of the HCD recording. Figure created in BioRender⁵⁰.