Adipose Tissue Response to Overfeeding in Insulin Resistance-Prone vs. Insulin Sensitive Humans
Condition: Insulin Resistance; Obesity
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      Obesity has become an epidemic worldwide. Data from our laboratory and others demonstrate
      that most of the excess morbidity from obesity is related to insulin resistance (IR). While
      total adiposity correlates with insulin resistance, not all obese individuals are IR. When
      obese IR individuals lose weight in response to caloric restriction, even moderate loss of
      body fat results in improved insulin sensitivity (IS). With massive weight loss, either
      dietary or surgical, even the most IR individuals can completely reverse their insulin
      resistance. But why is one individual IR at a BMI of 26 and another IS at a BMI of 35? There
      must be differences in the manner in which adipose cells/tissue respond to caloric excess and
      weight gain. One potentially unifying hypothesis with regard to obesity-associated insulin
      resistance is that those individuals who fail to respond to caloric excess/obesity with
      adequate adipocyte differentiation and expanded subcutaneous fat storage capacity develop
      increased circulating FFAs, ectopic fat deposition, stress on adipocytes, triggering
      localized and systemic inflammation and ultimately insulin resistance in skeletal muscle.

      Clearly, the best way to examine the human response to obesity is to challenge overweight
      individuals with the need to store excess triglyceride in adipose tissue. Specific aims are:

        1. Test the hypothesis that impaired adipogenesis and fat storage capacity are associated
           with insulin resistance by comparing 1) cell size distribution; 2) gene markers of
           adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone
           vs IS individuals subjected to caloric excess.

        2. Determine if circulating (daylong FFA, two-stage Insulin Suppression Test) and ectopic
           fat (MRI liver, CT abdomen) are worsened to a greater degree in IR-prone vs IS
           individuals subjected to caloric excess.

        3. Determine whether differences in inflammation and/or innate or adaptive immune response
           are associated with insulin resistance by comparing differences in resident dendritic
           cells, macrophages and their activation profiles, changes in T-cell subpopulations, and
           other inflammatory mediators in IR-prone vs IS individuals who are subjected to caloric
           excess via overfeeding.

        4. Exploratory: Evaluate IR-prone vs IS individuals for evidence of hypoxia and
           insufficient angiogenic response in response to caloric excess.
    


Intervention name(s): Over feeding
Intervention type(s): Other
Intervention description(s): Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: ectopic fat; obesity; triglyceride storage; adipocyte; overfeeding; intrahepatic fat; adipocyte proliferation; inflammation; macrophage