EDITORIAL October 29, 2021 October 29, 2021

Nutritional factors regulating behavior and biological clocks

DOI: 10.20945/2359-3997000000410

I was recently invited to write an editorial () about an excellent review () that put together a large amount of data showing the impact of nutrients on the regulation of gene expression and systemic inflammation. Over the last 50 years, changes in nutritional standards taking place in most regions of the world have reshaped human health parameters promoting an unprecedent increase in the prevalence of obesity and its comorbidities (). As shown by Correa and cols. (), components of the diet can regulate systemic metabolism by different means, such as activating cell receptors, modulating inflammation, promoting epigenetic modifications, and acting through microRNAs. Over the years, researchers have engaged most of their efforts to characterize the harmful and beneficial effects of nutrients on the most prevalent conditions associated with obesity, such as diabetes and cardiovascular diseases. However, there are several other health conditions that can be deteriorated in obesity. In this issue of the Archives of Endocrinology and Metabolism, two experimental studies provide advance in the mechanistic understanding of how dietary factors impact on anxiety-like behavior () and circadian clocks ().

In humans, there is evidence supporting the association between obesity and anxiety/depression. A meta-analysis evaluating 16 studies reported an odds ratio of 1.4, indicating a moderate level of positive association between both conditions (). Inflammation is believed to play an important mechanistic role in this scenario as in both obesity () and anxiety/depression () there is inflammation in distinct areas of the brain. Currently, pediatric obesity is one of the most serious health problems in the world. A child that develops obesity early in life can present cardiovascular disease up to a decade earlier than baseline population (). However, it is uncertain how the early development of obesity could affect behavior. With this question in mind, Lorena and cols. () evaluated an animal model fed on a high-fat diet from early life. They showed that markers of inflammation were significantly increased in the prefrontal cortex of obese rats and this was accompanied by behavioral changes compatible with the anxiety/depression phenotype. Because of the existence of confounding factors, the determination of behavioral phenotypes in animal models is complex (). To avoid biases, experimental approaches are optimized by the execution of several tests. In their model, Lorena and cols. () performed seven distinct tests to explore depression, anxiety and memory. In two tests, forced swimming test and novelty-suppressed feeding test, obese rats presented abnormalities, suggesting they have developed an anxiety/depression-like behavior. The study provides an elegant experimental evidence to support the association between obesity at an early age with anxiety and depression (), showing that diet-induced inflammation in the prefrontal cortex could provide a mechanistic link between both conditions.

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