Genetics have long been understood as potential culprits in a number of behavioral outcomes both related and unrelated to nutrition, perhaps with just as much pull as the environmental influences that surround us. When it comes to behaviors related to weight management, National Institutes of Health (NIH) researchers recently came across one gene present in both mice and humans which is strongly associated with cravings for fatty, sugary foods, according to a new study which appears in the Journal of Clinical Investigation.
 
The authors of the study investigated a gene, Prkar2a, which is highly expressed in a tiny brain region called the habenula, known for its activity in response to pain, stress, anxiety, sleep, and reward. In sum, it communicates with other regions of the brain in response to rewarding and punishing stimuli. That region has long been investigated for potential roles in mood disorders and addiction, however, its role in cravings is relatively under-studied. The gene functions by coding the enzyme protein kinase A, a central enzyme which speeds up reactions at an intracellular level in many species, and suppressing the gene in mice appeared to make them less likely to become obese than wild-type mice, which had normally-functioning Prkar2a.
 
“Years of cumulative data show that the seemingly simple idea of balancing caloric intake with energy expenditure is complex and influenced by many opposing drives that are exacerbated by overscheduled sedentary lifestyles, changes in the food supply, and genetics,” the authors of the study said. “As a major player in the regulation of the midbrain monoaminergic system, the Hb is a central structure that integrates rewards with cognition and emotion. While these Hb functions have been investigated in the context of substance abuse, a role for the Hb in obesity and susceptibility to the energy imbalance that drives preventable metabolic dysregulation is less clear.”
 
In the clinical trial, when both types of mice were given unlimited access to food, and specifically after fasting as well, those who were Prkar2a-negatvive ate less. Similarly, Prkar2a negative mice drank less of a sugar solution than the wild type mice. It appeared that suppressing the gene had a more pronounced effect on reducing fat cravings in female mice, and in reducing sugar solution cravings for male mice, particularly. In addition, suppressing this gene appeared to cause mice to be more inclined to exercise, running 2-3 times longer than wild type mice on a treadmill.
 
“Here we identify an unexpected role for Pkar2a in the Mhb in the simultaneous positive regulation of food rewards and negative effect on the drive to exercise, behaviors that were both reversed with R2A deficiency,” the authors wrote. “The diminishment of both drives is characteristic of the anhedonia observed in major depressive disorder, and LHb hyperactivation has been associated with both the neurobiological dysregulation and the motivational symptoms of depression […] In both obesity and substance abuse, the dysregulation of signaling and subsequent changes in reward circuitry can fuel the cycle of compulsive drug or compulsive food consumption.”
 
The authors concluded that these findings could inform future research in the efforts to prevent obesity and its accompanying risk for cardiovascular disease and diabetes.