Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans

Abstract

Objective Connective tissue growth factor (CTGF) is an important regulator of fibrogenesis in many organs. This study evaluated the interrelationship among adipose tissue CTGF expression, fat mass, and insulin resistance in humans. Methods This study examined (1) CTGF gene expression in human subcutaneous preadipocytes before and after inducing adipogenesis; (2) relationships among abdominal subcutaneous adipose tissue CTGF gene expression, body fat mass, and indices of insulin sensitivity, including the hepatic insulin sensitivity index and the hyperinsulinemic‐euglycemic clamp procedure in conjunction with stable isotope glucose tracer infusion, in 72 people who had marked differences in adiposity and insulin sensitivity; (3) localization of CTGF protein in subcutaneous adipose tissue; and (4) effect of progressive (5%, 11%, and 16%) weight loss on adipose tissue CTGF gene expression. Results CTGF was highly expressed in preadipocytes, not adipocytes. Adipose tissue CTGF expression was strongly correlated with body fat mass and both skeletal muscle and liver insulin sensitivity, and CTGF‐positive cells were predominantly found in areas of fibrosis. Progressive weight loss caused a stepwise decrease in adipose tissue CTGF expression. Conclusions It was concluded that increased CTGF expression is associated with adipose tissue expansion, adipose tissue fibrosis, and multi‐organ insulin resistance in people with obesity.

Metabolically healthy obesity: facts and fantasies

“…Compared with people who are lean, people with obesity have increased expression of genes for collagen I, IV, V, and VI and histological evidence of increased fibrosis, particularly pericellular fibrosis in omental adipose tissue and SAAT (131)(132)(133)(134)(135). In addition, we recently found that adipose tissue expression of connective tissue growth factor (CTGF), a matricellular protein that regulates tissue fibrosis, is positively correlated with body fat mass and inversely correlated with indices of wholebody, liver, and skeletal muscle insulin sensitivity (136). Adipose tissue expression of collagen genes and collagen content are also inversely correlated with insulin sensitivity in people with obesity, and decrease with weight loss (129,(137)(138)(139).…”

Management of Diabetes Mellitus in Patients with Chronic Liver Diseases

“…All these changes might cause vascular cell damage and angiogenesis. In addition to these changes, necrosis or apoptosis of acinar cells, proliferative and profibrinogenic of growth factors including platelet-derived growth factor (PDGF), TGF-α [21] and connective growth factor (CTGF) [23] are all involved in fibrogenesis. This pathway induces chronic pancreatitis characterized by atrophy and fibrosis of acinar cells, leading to exocrine and endocrine glandular dysfunction [20,21].…”

Insights into Molecular Mechanisms Underlying NAFLD by Protein-Protein Interaction Network Analysis of the Differentially Expressed Genes in NASH Patients.

“…Besides, aberrant CTGF expression is associated with many types of malignancies, diabetic nephropathy and retinopathy, arthritis, and cardiovascular diseases. Yoshino, J. showed that CTGF overexpression was associated with adipose tissue expansion and multi-organ insulin resistance in obese subjects (34). Colak, Y. et al demonstrated that CTGF serum levels might be a clinical marker for distinguishing those NAFLD patients with advanced brosis from those who do not (35).…”