Characterisation of the impact of systemic insulin resistance and its reversal on human brain responses to meal ingestion and food cues: a functional magnetic resonance imaging study.

Abstract

Altered corticolimbic regulation of appetite is implicated in the aetiology of obesity and type 2 diabetes, conditions more prevalent with age and associated with insulin resistance. This thesis characterises the impact of ageing, systemic insulin resistance before disease onset and, insulin sensitisation, on brain processing of satiation and satiety, furthering our understanding of the role of insulin in appetite control.
Brain responses to meal vs water ingestion, and the modulation of food image-evoked responses by a meal were examined using pseudo-continuous arterial spin labelling and blood oxygenation level dependent functional neuroimaging respectively, in healthy men/women aged 19.5-52.6 years, and insulin sensitive (IS) and resistant (IR) men. IR men were re-examined after 3-months lifestyle changes with metformin.
Ageing was associated with diminishing hunger-suppression and increasing insula, orbitofrontal (OFC) and anterior cingulate cortex activity after eating, and diminishing modulation of dorsolateral prefrontal cortex (DLPFC), OFC and striatal food image-evoked activity by the meal.
IR men had greater food restraint, weight/shape concern, and less hunger-suppression after eating. The insula activated in IR and deactivated in IS subjects after eating. IS, but not IR, subjects showed DLPFC, striatal and lingual gyrus activation increased to high- and decreased to low-calorie food images after eating, the opposite observed when fasted. Between-group comparisons revealed greater DLPFC activation to high- vs low-calorie food cues when fed, and low- vs high-calorie food cues when fasted in IR men. The intervention improved insulin sensitivity and glycaemic status, reduced post-prandial insula activity, and increased post-prandial low-calorie food cue-evoked activity.
Results indicate impaired satiation with exaggerated post-prandial interoceptive and reward centre activity, and diminishing sensitivity of inhibitory control and reward centre responses to external food cues to current nutritional status with ageing and systemic insulin resistance. Insulin sensitisation improves insulin resistant central processing of satiation and satiety, implicating insulin in appetite regulation.

Date of Award	2017
Original language	English
Awarding Institution	King's College London
Supervisor	Stephanie Amiel (Supervisor) & Fernando Zelaya (Supervisor)