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

Abstract

Context 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.

Decreased serum levels of thrombospondin‐1 in female depressed patients

“…Serum TSP-1 levels showed a significant positive correlation with BMI in females. 18 Thus, we also investigated whether BMI affected the TSP-1 levels of MDD-F in this study. It revealed that BMI did not affect serum TSP-1 levels.…”

“…A previous study indicated a relationship between BMI and serum TSP‐1 specifically in females. Serum TSP‐1 levels showed a significant positive correlation with BMI in females . Thus, we also investigated whether BMI affected the TSP‐1 levels of MDD‐F in this study.…”

“…A previous study indicated a relationship between BMI and serum TSP-1 specifically in females. 18 However, there was no significant difference in BMI between Cont-F and MDD-F (Table 1).…”

Adipose extracellular matrix remodelling in obesity and insulin resistance

“…Thrombospondin 1 (THBS1) is a large adhesive ECM glycoprotein expressed predominantly in visceral adipose tissues and its expression is elevated in insulin-resistant, obese humans [27,28]. In mice, HFD acutely induces Thbs1 expression in visceral adipose tissues and increases the circulating THBS1 level [29].…”

Thrombospondin-1 mediates multi-walled carbon nanotube induced impairment of arteriolar dilation

“…Another receptor for TSP-1 more commonly associated with regulation of angiogenesis, CD36, may also play a role in inhibiting eNOS by displacing it from intracellular caveolae (Shaul, 2003). The TSP-1/CD47/CD36 signaling axis has been implicated as a contributing factor, or in the etiology, to a number of disease states, including coronary artery disease (Celermajer et al, 1992; Schachinger et al, 2000), obesity and metabolic syndrome (Matsuo et al, 2015; Steinberg et al, 1996; Varma et al, 2008), hypertension (Boulanger, 1999; Panza et al, 1990), peripheral arterial disease (Smadja et al, 2011), diabetes mellitus (Cai & Harrison, 2000), stroke (Cho, 2012) among others (Kong et al, 2013; Roberts et al, 2012). …”