High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex

TY - JOUR

T1 - High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex

AU - Lauridsen, J K

AU - Olesen, R H

AU - Vendelbo, J

AU - Hyde, T M

AU - Kleinman, J E

AU - Bibby, B M

AU - Brock, B

AU - Rungby, J

AU - Larsen, A

PY - 2017

Y1 - 2017

N2 - Several studies link increasing body mass index (BMI) to cognitive decline both as a consequence of obesity per se and as a sequela of obesity-induced type 2 diabetes. Obese individuals are prone to a chronic low-grade inflammation as the metabolically active visceral fat produces proinflammatory cytokines. Animal studies indicate that these cytokines can cross the blood-brain barrier. Such crossover could potentially affect the immune system in the brain by inducing gene expression of proinflammatory genes. The relationship between obesity and neuroinflammation in the human brain is currently unknown. Therefore we aim to examine the relationship between BMI and gene expression of central inflammatory markers in the human frontal cortex. Microarray data of 141 neurologically and psychiatrically healthy individuals were obtained through the BrainCloud database. A simple linear regression analysis was performed with BMI as variable on data on IL10, IL1β, IL6, PTGS2 (COX2) and NOS2 (iNOS). Increasing BMI is associated with a decrease in the mRNA expression of IL10 (P=0.014) and an increase in the expression of NOS2 (iNOS; P=0.040). Expressions of IL10 and NOS2 (iNOS) were negatively correlated (P<0.001). The expression of IL10 was mostly affected by individuals with BMI ⩾40. Multiple linear regression analyses with BMI, age, sex and race as variables were performed in order to identify potential confounders. In conclusion, increasing BMI could affect the IL10-mediated anti-inflammatory defense in the brain and induce iNOS-mediated inflammatory activity.

AB - Several studies link increasing body mass index (BMI) to cognitive decline both as a consequence of obesity per se and as a sequela of obesity-induced type 2 diabetes. Obese individuals are prone to a chronic low-grade inflammation as the metabolically active visceral fat produces proinflammatory cytokines. Animal studies indicate that these cytokines can cross the blood-brain barrier. Such crossover could potentially affect the immune system in the brain by inducing gene expression of proinflammatory genes. The relationship between obesity and neuroinflammation in the human brain is currently unknown. Therefore we aim to examine the relationship between BMI and gene expression of central inflammatory markers in the human frontal cortex. Microarray data of 141 neurologically and psychiatrically healthy individuals were obtained through the BrainCloud database. A simple linear regression analysis was performed with BMI as variable on data on IL10, IL1β, IL6, PTGS2 (COX2) and NOS2 (iNOS). Increasing BMI is associated with a decrease in the mRNA expression of IL10 (P=0.014) and an increase in the expression of NOS2 (iNOS; P=0.040). Expressions of IL10 and NOS2 (iNOS) were negatively correlated (P<0.001). The expression of IL10 was mostly affected by individuals with BMI ⩾40. Multiple linear regression analyses with BMI, age, sex and race as variables were performed in order to identify potential confounders. In conclusion, increasing BMI could affect the IL10-mediated anti-inflammatory defense in the brain and induce iNOS-mediated inflammatory activity.

KW - Adolescent

KW - Adult

KW - Aged

KW - Body Mass Index

KW - Child

KW - Child, Preschool

KW - Cyclooxygenase 2/genetics

KW - Female

KW - Frontal Lobe/metabolism

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Interleukin-10/genetics

KW - Interleukin-1beta/genetics

KW - Interleukin-6/genetics

KW - Linear Models

KW - Male

KW - Middle Aged

KW - Nitric Oxide Synthase Type II/genetics

KW - Obesity/metabolism

KW - Overweight/metabolism

KW - RNA, Messenger/metabolism

KW - Thinness/metabolism

KW - Young Adult

U2 - 10.1038/tp.2016.259

DO - 10.1038/tp.2016.259

M3 - Journal article

C2 - 28244985

SN - 2158-3188

VL - 7

JO - Translational Psychiatry

JF - Translational Psychiatry

M1 - e1044

ER -