Insulin Resistance and Reward
Condition: Obesity
MeSH terms: Obesity; Insulin Resistance
Study type: Interventional
Phase: Phase 2

Summary: 
      Obesity is a common problem in the Veteran population as at least 1 in 3 Veterans are obese.
      When obese people eat food they have less response in areas of the brain that sense pleasure
      (reward). Decreased pleasure response to food predicts future weight gain. It is not known if
      this poor brain response is reversible or why obese people's brains respond this way. Insulin
      in the brain regulates the brain's sensing of pleasure. As people gain weight the function of
      insulin becomes impaired. The investigators will study if impaired function of insulin is
      related to a poor brain response to food and if this brain response predicts voluntary intake
      of food and response to a diet. The investigators will also study if improving the function
      of insulin with weight loss improves the brain response. These studies will improve the
      understanding as to why weight loss is difficult and inform us if improving insulin signaling
      is a potential way to treat obesity.
    

Detailed description: 
      The current research proposal will investigate the relationship of insulin sensitivity to
      brain reward signaling. In most obese individuals, 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 primary research outcomes of the proposed study are: 1) insulin sensitivity determined by
      hyperinsulinemic euglycemic clamp, 2) food consumption-induced neural activation as
      determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI)
      scanning, 3) caloric intake at a buffet meal, and 4) weight loss during a weight loss
      intervention. Based on screening and baseline outcome assessments half of participants will
      be enrolled in a weight loss intervention and then repeat outcomes measures after
      intervention. Others will only complete baseline outcome measures. Secondary measures of the
      study include whole brain activation analyses, neuroendocrine hormone measurement at the time
      of imaging, psychometric measures including eating behaviors and personality characteristics,
      and measures of reward sensitivity.
    

Intervention name(s): Weight loss
Intervention type(s): Behavioral
Intervention description(s): Obese Veterans will undergo dietary education for weight loss or weight maintenance
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are assigned to two groups in parallel for the duration of the study. There is a dietary weight loss intervention aiming for ~5-10% weight loss
Masking: Single (Participant)
Primary purpose: Other
Keywords: Insulin resistance; Consummatory Reward