Neurocognitive and developmental perspectives of obesity

This special edition of the International Journal of Developmental Neuroscience is focused on “Neurocognitive and Developmental Perspectives of Obesity”. Obesity is a global health concern with over 600 million obese adults around the world and over 40 million obese children under the age of five. Further adding to the problem, global obesity rates continue to rise with no obvious signs of stabilization. Although energy homeostasis is heavily regulated by the brain, it is also becoming more apparent that diet-induced obesity is causing neurocognitive dysfunction. This special edition focuses on elucidating the complex relationship between brain function and energy homeostasis to advance our understanding of this global problem. In the first manuscript by Guarnieri et al., the effects of a high-fat diet on microRNA-155 (mir-155), an important molecular regulator of inflammation, were evaluated. Diet-induced obesity reduced the levels of mir-155 by over 80% in the nucleus accumbens, a brain region closely associated with reward and motivated behavior. Knockout of mir-155 caused mice to consume more of a high-fat diet compared to wild type controls resulting in significant body weight gain. No changes in metabolism were observed in the knockout mice, indicating that mir-155 is a novel regulator of food intake and body weight. Auguste et al. explore the behavioral and metabolic consequences of perinatal dietary deficiency of the essential nutrient omega-3 polyunsaturated fatty acid during development. This resulted in reduced omega-3 polyunsatureated fatty acids in the brain. Furthermore, these animals had elevated sensitivity to sucrose reward, elevated weight gain on a high-fat diet, decreased activity, and increased anxiety-like behavior. This work greatly enhances our understanding of the effects of nutrient deficiency on energy balance and behavior. Neuropeptide Y (NPY) and proopiomelanocortin (POMC) are neuropeptides in the brain which regulate energy balance. Klein et al. have demonstrated that exposure of a pregnant mouse to a high-fat diet alters expression of NPY and POMC in the brains of embryos. These findings have profound implications for metabolic reprogramming in embryonic brains resulting from the consumption of a high fat diet during pregnancy. Although birthweight that is either too high or too low is associated with multiple neurodevelopmental disorders, the role of maternal nutrition in these disorders is poorly understood. Here, Thanos et al. discovered that low maternal protein consumption, a model for suboptimal fetal growth and small birth weitht, have decreased binding of mu-opioid receptor and dopamine D1 receptor in reward-associated brain regions. This may contribute to some of the behavioral abnormalities associated with low birthweight. Furthermore, Ogassawara et al. have explored multigenerational effects of maternal food restriction followed by a hypercaloric diet for the offspring on energy homeostasis in third generation mice. When challenged with lipopolysaccharide, the expression of glial fibrillary acidic protein was altered in multiple brain regions. In order to better understand underlying behavioral mechanisms of obesity, models of ingestive behavior need to be further explored. In this issue, Johnson has reviewed the use of licking behavior; by evaluating the microstructure of licking, licking bouts and bursts can be identified and quantified. This behavior reflects the palatability of the liquid and allows for the study of the underlying neurobiological mechanisms of food avoidance and food acceptance. The role of obesity in causing cognitive dysfunction has become a prominent area of research. It is now clear that metabolic disease can impair neuronal function in the brain which results in significant behavioral and cognitive deficits in animal models. Kasper et al. have extended our understanding of this mechanism by implicating adipose tissue-derived ecto-nucleotide pyrophosphatase phosphodiesterase-1 (ENPP1), an inhibitor of insulin signaling, as a regulator of the adipose-brain axis and the behavioral deficits in metabolic disease. ENPP1 overexpression in adipose tissue impairs hippocampal physiology and Morris Water Mazer performance in mice. Furthermore, Kaizer et al. evaluated the effects of a high-fat diet on the choloinergic system in the brain. Acetylcholinesterase activity was decreased by 20% in synaptosomes from the hippocampus and cerebellum in animals fed a high-fat diet. In addition, the purinergic system was adversely effected as adenine nucleotide hydrolysis was significantly reduced. These data indicate a mechanistic link between a high fat diet and cognitive dysfunction. Lastly, Iqbal et al. explore the relationship between cholesterol efflux from adipose tissue and estradiol levels in people. The authors discovered that estradiol levels are directly associated to high density lipoptotein cholesterol with higher estradiol promoting higher cholesterol efflux. These results were discussed and reviewed in the context of a growing body of research indicating that cholesterol metabolism and adipose tissue function are associated with vascular dementia. Altogether, the manuscripts in this special edition highlight the relationship between energy balance, nutrition, and brain function throughout development and into adulthood. It is clear that obesity stemming from modern diets can negatively impact brain development and function. With sustained research efforts, this enhanced understanding of the developmental, nutritional, genetic, and behavioral mechanisms of energy balance may lead to new therapeutic strategies to treat obesity.