Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome

• Published in: Metabolism, clinical and experimental Vol. 64; no. 11; pp. 1490 - 1499
• Main Authors: Matsuo, Yoshiyuki, Tanaka, Masashi, Yamakage, Hajime, Sasaki, Yousuke, Muranaka, Kazuya, Hata, Hiroaki, Ikai, Iwao, Shimatsu, Akira, Inoue, Mayumi, Chun, Tae-Hwa, Satoh-Asahara, Noriko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: Aged; Biological marker; Biomarkers - blood; Biomarkers - metabolism; Diabetes; Endocrinology & Metabolism; Female; Humans; Intra-Abdominal Fat - metabolism; Male; Metabolic syndrome; Metabolic Syndrome - diagnosis; Metabolic Syndrome - metabolism; Middle Aged; Obesity; Obesity - diagnosis; Obesity - metabolism; Obesity - therapy; Postmenopause; Premenopause; RNA, Messenger - metabolism; Thrombospondin 1; Thrombospondin 1 - blood; Thrombospondin 1 - genetics; Thrombospondin 1 - metabolism; Weight Loss; IRI; LDL-C; SAT; VAT; Biological marker; ALT; WC; Metabolic syndrome; THBS1; HDL-C; DBP; TGF-β; FSH; HbA1c; BMI; γ-GTP; SBP; Obesity; AST; Thrombospondin 1; ECM; HOMA-IR; TG; hsCRP; Diabetes; FPG; high sensitivity C-reactive protein; thrombospondin 1; low-density lipoprotein cholesterol; alanine aminotransferase; γ-glutamyl transpeptidase; systolic blood pressure; diastolic blood pressure; high-density lipoprotein cholesterol; subcutaneous adipose tissue; immunoreactive insulin; visceral adipose tissue; homeostasis model assessment of insulin resistance; follicle-stimulating hormone; waist circumference; body mass index; triglycerides; aspartate aminotransferase; transforming growth factor-β; fasting plasma glucose; hemoglobin A1c; extracellular matrix
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2015.07.016

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. In this study, we aimed to determine the clinical significance of THBS1 as a novel biological marker of visceral obesity, metabolic syndrome, and diabetes. 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. 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. 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.