High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex
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High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex. / Lauridsen, J K; Olesen, R H; Vendelbo, J; Hyde, T M; Kleinman, J E; Bibby, B M; Brock, B; Rungby, J; Larsen, A.
In: Translational Psychiatry, Vol. 7, e1044, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 7
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
M1 - e1044
ER -
ID: 196167595