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.
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.
Amanda C
AC
Mitchell
Rehana K
RK
Leak
Michael J
MJ
Zigmond
Judy L
JL
Cameron
Károly
K
Mirnics
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015992:Body Mass Index; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D002421:Caudate Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation; D000067758:Glucagon-Like Peptide-2 Receptor; D008253:Macaca mulatta / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D009044:Motor Cortex / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics*; D018027:Receptors, Glucagon / Q000235:genetics
D000067758:Glucagon-Like Peptide-2 Receptor; D018027:Receptors, Glucagon; D011972:Receptor, Insulin; D019950:Mitogen-Activated Protein Kinase 1