Insulin Resistance and Reward Signaling in Obesity

The current research proposal will investigate the relationship of insulin sensitivity to brain reward signaling. In most individuals with obesity, insulin signaling is impaired (insulin resistance). Preclinical animal studies suggest that insulin resistance in brain regions important for reward contribute to overeating. This proposal aims to test these hypotheses in humans and to determine if these characteristics are pertinent to clinical outcomes (food intake and weight loss). In humans increased body mass index (BMI) and weight gain occur with decreased food consumption-induced neural activation (consummatory reward) in the caudate of the dorsal striatum. It has been speculated that diminished consummatory reward causes overeating and prevents weight loss, however, this hypothesis has not been directly tested. Further, mechanisms for impaired food consumption-induced neural activation in obesity have not been investigated.

The research outcomes of the proposed study are: 1) taste-induced neural activation as determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI) scanning, 2) caloric intake at a buffet meal, and 3) food craving. Based on screening and baseline outcome assessments participants with insulin resistance (metabolically unhealthy obesity) will be enrolled in a weight loss intervention to lose 5-10% body weight and then repeat outcomes measures after intervention. Those who are metabolically healthy at baseline (MHO) will only complete baseline outcome measures.

Inclusion criteria

• Age 25-60yoa, inclusive.
• BMI 30.0 and 45.0 kg/m2, inclusive.
• Normal visual acuity with correction.
• Able to travel regularly to the St. Louis VA and Washington University for research visits.
• Completed signed informed consent form.

Exclusion criteria

• Current or history of significant psychiatric disease, including Binge Eating Disorder (BED).
• Current or history of significant substance abuse or extended use of tobacco.
• Contraindications for MRI (e.g., pregnancy, claustrophobia, pacemaker, circumference > 54 inches, weight > 400 lbs, etc.);
• Significant cardiovascular, pulmonary, renal, liver, neurologic, or metabolic disease.
• Diabetes mellitus.
• Significant anemia.
• Treatment with a medication the affects insulin sensitivity.
• Treatment with centrally acting medications.
• Frequent shift work.
• Significant in-mobility or unable to lay on back still for 1 hour.
• History of bariatric surgery.
• Food allergies/ intolerance that would prevent completing study.
• Symptoms concerning for untreated active mental health disease