title: Progranulin is increased in human and murine lipodystrophy.
abstract: OBJECTIVE
  Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far.
  
  
  METHODS
  Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD.
  
  
  RESULTS
  Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation.
  
  
  CONCLUSIONS
  Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin.
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany. Electronic address: konstanze.miehle@medizin.uni-leipzig.de.
authors: Konstanze
authors: K
authors: Miehle
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
authors: Thomas
authors: T
authors: Ebert
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
authors: Susan
authors: S
authors: Kralisch
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany.
authors: Annett
authors: A
authors: Hoffmann
authors: Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Liebigstr. 27, 04103 Leipzig, Germany.
authors: Jürgen
authors: J
authors: Kratzsch
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany.
authors: Haiko
authors: H
authors: Schlögl
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany.
authors: Michael
authors: M
authors: Stumvoll
authors: Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
authors: Mathias
authors: M
authors: Fasshauer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D000077155:Granulins; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008060:Lipodystrophy / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D000077153:Progranulins; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: C492314:GRN protein, human; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D000077153:Progranulins; D012333:RNA, Messenger; D002097:C-Reactive Protein; C415771:metreleptin
keywords: Adipokine; Adipose tissue; Leptin treatment; Lipodystrophy; Progranulin