The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity
Condition: Neural Response in Caudate; Weight Loss Trial; Impulsivity
MeSH terms: Weight Loss; Impulsive Behavior
Study type: Interventional

Summary: 
      The aims of this project are to determine if dietary supplementation with NOPE-EGCG
      (PhosphoLeantm, 30mg NOPE+20mg EGCG per capsule) can:

        -  rescue striatal function,

        -  increase adherence to a diet,

        -  reduce weight-gain after a diet,

        -  improve performance on impulsivity, go/no-go tasks, and negative outcome learning, and

        -  shift fat and sweet preference in overweight/obese human subjects

      Secondary hypotheses: Baseline brain; perceptual and cognitive measures will be associated
      with diet, insulin sensitivity and may vary with genotype (TaqA1 1A polymorphism).
    

Detailed description: 
      In prior studies we have demonstrated an inverse relationship between body mass index and
      response in the dorsal striatum (DS) during consumption of a palatable milkshake (Stice et
      al. 2008). We have also shown that the magnitude of the reduced response predicts weight
      gain, especially in individuals who carry a copy of the A1 allele of the taq1A polymorphism
      (Stice et al. 2008). Since the A1 allele is associated with reduced striatal D2 receptors
      (Jonsson et al. 1999, Noble 2003, Noble et al. 1991, Pohjalainen et al. 1998, Ritchie et al.
      1998, Thompson et al. 1997), this finding implicates the dopamine system in the reduced blood
      oxygen level dependent (BOLD) response. Our results also indicate that this reduced response
      is a consequence, rather than a cause of obesity, since gaining weight (Stice et al. 2010),
      but not risk for obesity (Stice et al. 2011) (by virtue of parental obesity), is associated
      with reduced DS response to palatable food. Taken together the results indicate that
      increased adiposity is associated with blunted DS response to palatable food that may reflect
      altered dopamine signaling. More recently we determined that reduced DS responses in
      overweight and obese subjects are associated with increased impulsivity measured with the
      Barratt Impulsiveness Scale and a go no/no-go task (Babbs et al, In Press).

      Related to these findings in humans, preliminary work in rodents shows that exogenous
      administration of N-Acylethanolamines, such as oleoylethanolamine (OEA) can normalize
      high-fat diet induced dopamine decreases in DS and possibly induce a shift in preference
      (Tellez et al., In Press). Human testing of OEA supplementation is possible based on the
      availability of a dietary supplement containing the OEA precursor NOPE-EGCG ((PhosphoLEANtm,
      100 mg NOPE+50mg EGCG per capsule). PhosphoLEAN has been shown to enhance adherence to
      dietary advice in overweight healthy subjects (Rondanelli et al. 2009, Mangine et al. 2012).

      We therefore propose a double-blind cross-over study to test whether PhosphoLean will rescue
      striatal function, increase adherence to a diet, reduce weight-gain after a diet, improve
      performance on impulsivity, go/no-go tasks, and negative outcome learning, and shift fat and
      sweet preference in overweight/obese human subjects.
    

Intervention name(s): PhosphoLean; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): PhosphoLean supplied by Cheminutra (White Bear Lake, MN). PhosphoLean® N-Oleoyl-PE + EGCG (NOPE + EGCG) is a proprietary phosphobioflavonic complex of N-oleoyl-phosphatidyl-ethanolamine (NOPE), which contains oleoyl ethanolamine (OEA) bound to phosphatidylethanolamine (PE), and epigallocatechin gallate (EGCG).; Placebo consists of rice flour
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science