Effect of Intranasal Insulin on Cognitive Processes and Appetite

This study investigates the effect of intranasal insulin on cognitive processes (behavioural and neural) in healthy lean and obese female adults. All subjects will receive a single-dose of intranasal insulin and/or placebo (on different days) before participating in several cognitive tasks.

It is well established that eating behaviour is affected by metabolic signals (e.g. insulin, ghrelin, serotonin) and is also modulated via food reward processes. However, in humans, eating behaviour is a complex process, which involves habits, long-term goals and social interaction. Thus, recently it has been proposed that higher cognitive processes such as inhibitory control, attention and memory also modulate eating.

Insulin seems to be involved in both metabolic processes and cognitive processes. In the last decade it has been shown that intranasal administration of insulin decreases food intake, especially in women, and enhances thermogenesis and memory. In addition intranasal insulin administration has been shown to affect brain areas related to homeostatic control, reward and memory.

In the proposed study the investigators will examine the effect of intranasal insulin administration on eating, and on metabolic, reward and cognitive processes and their potential interplay. The investigators will also study the effect of body weight on the actions of insulin on these processes.

Eligibility Criteria:
Inclusion Criteria:

* Healthy female subjects
* Age 18-65 years at start of the study
* Body Mass Index (BMI) between 18 and 25 kg/m2 for the lean group and between 30 and 40 kg/m2 for the obese group
* Right-handedness (including left-handers could bias the results because of the laterality of brain functions)
* Ability to give informed consent
* Fluent English speaking
* Willingness to be informed about chance findings of pathology

Exclusion Criteria:

* Subjects who have a non-removable metal object in or at their body, such as, for example: Heart pace-maker, artificial heart valve, metal prosthesis, implants or splinters, non-removable dental braces
* Tattoos, that are older than 15 years
* Claustrophobia
* Limited temperature perception and/or increased sensitivity to warming of the body
* Pathological hearing ability or an increased sensitivity to loud noises
* Lack of ability to give informed consent
* Operation less than three months ago
* Simultaneous participation in other studies that involve drugs intake or blood spending
* Acute illness or infection during the last 4 weeks
* Cardiovascular disorders (e.g., hypertrophic cardiomyopathy, long QT syndrome)
* Moderate or severe head injury
* Eating disorders
* No metabolic (e.g. metabolic disorder, diabetes, insulin resistance), psychological (e.g. depression) or neurological (e.g. epilepsy, headache disorder, multiple sclerosis, traumatic brain injuries) diseases or medication in relation to these diseases.
* Intake of any medication that can interfere with the drug or measurements.
* Current weight loss regimens, or more then 5kg weight loss in the last 3 months
* Smoking
* Current pregnancy or breastfeeding
* Current or past history of drug or alcohol dependency - alcohol consumption exceeding 12 units a week
* Food allergies (e.g. peanut allergy lactose and gluten intolerance) or vegetarian/vegan diet
* Disliking the study lunch