title: Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome.
abstract: BACKGROUND
  Thrombospondin 1 (THBS1 or TSP-1) is an adipose-derived matricellular protein, which has recently been highlighted as a potential mediator of insulin resistance and adipose inflammation in obesity.
  
  
  OBJECTIVE
  In this study, we aimed to determine the clinical significance of THBS1 as a novel biological marker of visceral obesity, metabolic syndrome, and diabetes.
  
  
  METHODS
  The THBS1 mRNA level was quantified with real-time PCR in human adipose tissues obtained from 16 non-obese subjects. The relationships between serum THBS1 level and obesity/diabetes traits as well as the diagnostic components of metabolic syndrome were assessed in 164 normal-weight or overweight/obese subjects (78 males and 86 females; mean age, 50.4; mean BMI, 29.8) with analysis of covariance (ANCOVA) and regression analyses.
  
  
  RESULTS
  THBS1 was predominantly expressed in visceral adipose tissues relative to subcutaneous adipose tissues (P<0.001). The visceral THBS1 expression was positively associated with the body mass index (BMI; γs=0.54, P=0.033). ANCOVA demonstrated that the THBS1 level is associated with abdominal obesity (P<0.001), hyperglycemia (P=0.02), and hypertension (P=0.04). Multivariable regression analysis suggested an association between serum THBS1 and fasting plasma glucose levels. The associations between serum THBS1 levels and obesity/diabetes traits were found preferentially in women (BMI, γs=0.30, P=0.05; FPG, γs=0.26, P=0.016). Subanalyses demonstrated that the association with obesity traits was predominantly found in premenopausal women (BMI, γs=0.41, P=0.007), whereas the association with diabetes traits was predominant in postmenopausal women (HbA1c, γs=0.38, P=0.01). During medical weight reduction treatment, the change in the serum THBS1 level was associated with the change in BMI and HbA1c in pre- and postmenopausal women, respectively.
  
  
  CONCLUSIONS
  Serum THBS1 is a useful biological marker of obesity and metabolic syndrome in Japanese subjects, particularly in women. THBS1 may act as a critical circulating factor that couples obesity with metabolic syndrome and diabetes in humans.
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Yoshiyuki
authors: Y
authors: Matsuo
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Masashi
authors: M
authors: Tanaka
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Hajime
authors: H
authors: Yamakage
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Yousuke
authors: Y
authors: Sasaki
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Kazuya
authors: K
authors: Muranaka
authors: Department of Surgery, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Hiroaki
authors: H
authors: Hata
authors: Department of Surgery, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Iwao
authors: I
authors: Ikai
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan.
authors: Akira
authors: A
authors: Shimatsu
authors: Division of Metabolism, Endocrinology & Diabetes (MEND), Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors: Mayumi
authors: M
authors: Inoue
authors: Division of Metabolism, Endocrinology & Diabetes (MEND), Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: taehwa@med.umich.edu.
authors: Tae-Hwa
authors: TH
authors: Chun
authors: Division of Diabetic Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan. Electronic address: nsatoh@kuhp.kyoto-u.ac.jp.
authors: Noriko
authors: N
authors: Satoh-Asahara
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D017698:Postmenopause; D017697:Premenopause; D012333:RNA, Messenger / Q000378:metabolism; D019700:Thrombospondin 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D019700:Thrombospondin 1
keywords: Biological marker; Diabetes; Metabolic syndrome; Obesity; Thrombospondin 1