title: High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex.
abstract: 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.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: J K
authors.initials: JK
authors.lastname: Lauridsen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: R H
authors.initials: RH
authors.lastname: Olesen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Vendelbo
authors.affiliation: Lieber Institute for Brain Development, Baltimore, MD, USA.|Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Hyde
authors.affiliation: Lieber Institute for Brain Development, Baltimore, MD, USA.|Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Kleinman
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus C, Denmark.
authors.forename: B M
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Brock
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.|Center for Diabetes Research, Gentofte University Hospital. Hellerup, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Rungby
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Larsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human