Gene transcripts associated with BMI in the motor cortex and caudate nucleus of calorie restricted rhesus monkeys

Obesity affects over 500 million people worldwide, and has far reaching negative health effects. Given that high body mass index (BMI) and insulin resistance are associated with alterations in many regions of brain and that physical activity can decrease obesity, we hypothesized that in Rhesus monkeys (Macaca mulatta) fed a high fat diet and who subsequently received reduced calories BMI would be associated with a unique gene expression signature in motor regions of the brain implicated in neurodegenerative disorders. In the motor cortex with increased BMI we saw the upregulation of genes involved in apoptosis, altered gene expression in metabolic pathways, and the downregulation of pERK1/2 (MAPK1), a protein involved in cellular survival. In the caudate nucleus with increased BMI we saw the upregulation of known obesity related genes (the insulin receptor (INSR) and the glucagon-like peptide-2 receptor (GLP2R)), apoptosis related genes, and altered expression of genes involved in various metabolic processes. These studies suggest that the effects of high BMI on the brain transcriptome persist regardless of two months of calorie restriction. We hypothesize that active lifestyles with low BMIs together create a brain homeostasis more conducive to brain resiliency and neuronal survival.

► We analyzed gene expression changes in motor regions of the brain associated with BMI.
► Genes involved in apoptosis and metabolism were upregulated in the motor cortex.
► Expression of the insulin and GLP-2 receptors were increased in the caudate nucleus.
► The phosphorylation of ERK1/2, a survival kinase, was significantly decreased at high BMIs.
► Brain resiliency and neuronal survival are promoted at low BMIs.