Is there a common biology underlying both obesity and obesity-related behaviors?
Is there a common biology underlying both obesity and obesity-related behaviors? Despite a large body of evidence showing that obesity is associated with several adverse health outcomes, the underlying mechanisms governing obesity-related behaviors are poorly understood. Unless we understand what drives our inability to resist the temptation of calorie-dense foods, we will not be able to devise strategies to combat the global obesity epidemic. In a contemporary context, we are familiar with the stereotype of obese individuals as “headless, hungry and unhealthy” (Rebecca Puhl and colleagues, Yale University) that portray them as weak-willed, susceptible to over-eating and therefore vulnerable to poor health. In a recent study, we show that the relationships between obesity and obesity-related behaviors may be much more complex. We studied the commonly carried risk variant of the obesity-linked gene, FTO and showed that in addition to increasing body mass index (BMI) when individuals age, it also reduces brain function within regions intrinsic to impulse control and taste-responsiveness. We suggest that these reductions in brain function in the ventro-medial prefrontal cortex (vmPFC) may be responsible for increasing impulsivity and a preference for calorie-dense foods during aging in individuals who carry the obesity-risk allele of FTO.
In participants within the Baltimore Longitudinal Study of Aging (BLSA), risk allele carriers of the FTO SNP rs1410285 show greater increases in BMI over time (panel-A) and a reduction in brain function within the medial prefrontal cortex (mPFC), measured by 15O-water PET imaging (panel-B). Longitudinal decreases in mPFC function within regions important for impulse control and taste responsiveness may in turn, mediate observed increases in impulsivity and a greater intake of dietary fat (panel-C) in obesity-risk allele carriers of FTO.
NEO-PI-R; NEO Personality Inventory-revised. Figure modified with permission from Yi-Fang Chuang et al; FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain function, implusivity and diet, Molecular Psychiatry, 2014, [Epub ahead of print]
Fig-4. The fat mass and obesity-related gene (FTO) exerts pleiotropic longitudinal actions on body mass index (BMI) as well as brain function, impulsivity and macronutrient intake, suggesting shared biological mechanisms underlying a predisposition to obesity as well as obesity-related behaviors.