title: Markers of inflammation are heritable and associated with subcutaneous and ectopic skeletal muscle adiposity in African ancestry families.
abstract: Abstract Background: Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking.
  
  
  METHODS
  To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m(2)].
  
  
  RESULTS
  After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] ranged from 33% (TNFα) to 40% (CRP); all P<0.01. Higher CRP, IL-6, and TNF-α were associated with lower subcutaneous AT around skeletal muscle (r=-0.13 to -0.19, P<0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r=-0.10, P<0.05), hyperinsulinemia (r=0.12, P<0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.17, P<0.01).
  
  
  CONCLUSIONS
  Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, USA. miljkovici@edc.pitt.edu
authors.forename: Iva
authors.initials: I
authors.lastname: Miljkovic
authors.forename: Allison L
authors.initials: AL
authors.lastname: Kuipers
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Clareann H
authors.initials: CH
authors.lastname: Bunker
authors.forename: Alan L
authors.initials: AL
authors.lastname: Patrick
authors.forename: Victor W
authors.initials: VW
authors.lastname: Wheeler
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D002828:Choristoma / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000033:anatomy & histology; D014300:Trinidad and Tobago; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein