title: Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy.
abstract: OBJECTIVE
  Lipodystrophy is the major complication of antiretroviral therapy in HIV-infected patients. Its pathophysiology is not well understood, but has been linked to antiadipogenic effects of antiretroviral drugs. Lipin represents a newly characterized protein that is critical for adipocyte differentiation, and lipin deficiency leads to lipodystrophy in the mouse. The objective of this study was to determine whether altered lipin gene expression is associated with HIV lipodystrophy in humans.
  
  
  METHODS
  We measured lipin mRNA levels in subcutaneous abdominal and femoral-gluteal adipose tissue biopsies from HIV-infected patients with or without lipodystrophy, and in healthy controls. Real-time reverse transcription-PCR was performed to quantitate total lipin expression levels, and expression of two lipin isoforms (lipin-alpha and -beta) that are generated by alternative mRNA splicing.
  
  
  RESULTS
  As predicted from studies with mice, lipin mRNA levels were correlated with limb fat mass in HIV patients, with lower lipin levels in patients with lipodystrophy than those without lipodystrophy. Unexpectedly, however, this was explained by an increase in lipin-beta expression in HIV patients without lipodystrophy compared to patients with lipodystrophy and control subjects. In addition, lipin expression levels were inversely correlated with adipose tissue expression of inflammatory cytokines interleukin (IL)-6, IL-8 and IL-18, which typically increase in HIV-associated lipoatrophy.
  
  
  CONCLUSIONS
  Elevated lipin expression levels are associated both with the maintenance of greater fat mass and lower cytokine expression in HIV-infected patients. Based on the demonstrated role for lipin in promoting lipogenic gene expression, these observations raise the possibility that variations in lipin levels may contribute to variations in adipose tissue mass and function that distinguish HIV patients with and without lipodystrophy.
authors.affiliation: Department of Infectious Diseases, The Centre of Inflammation and Metabolism, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Lindegaard
authors.forename: L F
authors.initials: LF
authors.lastname: Larsen
authors.forename: A-B E
authors.initials: AB
authors.lastname: Hansen
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: K
authors.initials: K
authors.lastname: Reue
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005121:Extremities; D015870:Gene Expression / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000032:analysis; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D010711:Phosphatidate Phosphatase; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007378:Interleukins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase