title: Obesity Is Associated With Gene Expression and Imaging Markers of Iron Accumulation in Skeletal Muscle.
abstract: BACKGROUND
  Different genetic and imaging iron markers are known to be increased in the liver, adipose tissue, and brain of obese subjects.
  
  
  OBJECTIVE
  We aimed to investigate these markers in human skeletal muscle. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: Markers of iron accumulation were measured in three different territories: Iron gene markers (TFRC1, TF, SLC11A2, FTL, FTH1, and SLC40A1) were studied in abdominal rectus abdominis (Cohort 1, n = 26) and quadriceps (Cohort 2, n = 13) muscle using real-time PCR, whereas paravertebral muscle R2* signal (as surrogate of iron content) (Cohort 3, n = 43) was evaluated by means of magnetic resonance imaging.
  
  
  METHODS
  In a subgroup of 14 obese participants from Cohort 3, a diet-induced weight loss was performed.
  
  
  RESULTS
  Rectus abdominis muscle age-adjusted gene expression of SLC40A1 (ferroportin) (r = 0.47; P = .04), SLC11A2 (r = 0.50; P = .03) and CYBA (r = 0.62; P = .006) increased with body fatness. In obese participants from Cohort 1, muscle CYBA gene expression was positively correlated with serum ferritin. This association was replicated in quadriceps from obese participants (Cohort 2). Paravertebral muscle R2* was positively associated with body mass index, waist circumference, and fat mass (measured by dual-energy x-ray absorptiometry) in parallel with hepatic iron content, serum ferritin, and hepcidin. In multivariate regression analyses, obesity parameters (P < .0001) and hsCRP concentration (P < .05) contributed independently to the variance of sex-, serum hepcidin- and age-adjusted muscle R2*. Of note, weight loss intervention resulted in decreased muscle R2* (P = .02) in correlation with the change of serum ferritin (r = 0.69; P = .01).
  
  
  CONCLUSIONS
  These findings emphasize a significant iron accumulation in human skeletal muscle in association with obesity. The mechanisms implicated in these observations should be studied further.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: José María
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Blasco
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Gemma
authors.initials: G
authors.lastname: Xifra
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Karczewska-Kupczewska
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stefanowicz
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Matulewicz
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Straczkowski
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (J.M.M.-N., G.X., F.O., W.R., J.M.F.-R.), Institut d'Investigació Biomèdica de Girona, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CB06/03/010) and Instituto de Salud Carlos III, Girona, 17007 Spain; Department of Radiology (G.B., J.P.), Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, 17007 Spain; Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Medical University of Białystok, 15-089 Białystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D050154:Adiposity / Q000235:genetics; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003430:Cross-Sectional Studies; D003952:Diagnostic Imaging; D004038:Diet, Reducing; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism*; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D007501:Iron; D019255:NADPH Oxidases; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C086986:CYBA protein, human