Enhanced ANGPTL2 expression in adipose tissues and its association with insulin resistance in obese women

Abstract

Angiopoietin-like protein 2 has been proposed to be a key mediator linking obesity and insulin resistance. However, no detailed study of ANGPTL2 expression in human adipose tissues has yet been reported. To investigate the pattern and regulation of ANGPTL2 expression in human adipose tissues in obesity and its related diseases, we recruited 32 non-diabetic and 13 type 2 diabetic obese women and 32 normal-weight women. ANGPTL2 mRNA was expressed at a similar level in visceral and subcutaneous adipose tissues. Adipose tissue ANGPTL2 mRNA was much higher in obese patients. Adipose tissue ANGPTL2 mRNA and serum ANGPTL2 levels showed strong associations with metabolic parameters associated with insulin resistance. In adipose tissue, ANGPTL2 mRNA was closely correlated with the expression of genes involved in inflammation and ER stress. ANGPTL2 mRNA was principally expressed in adipocytes, and its expression was markedly higher in the adipocyte but non-adipocyte fraction of obese adipose tissues. Culture of human adipocytes under conditions mimicking the microenvironment of obese adipose tissue (especially, increased ER stress) stimulated ANGPTL2 gene expression and secretion. In addition, co-culture of adipocytes and macrophages suggested that ANGPTL2 excessively produced by adipocytes, may contribute inflammation and remodeling in obese adipose tissues, thereby promoting insulin resistance.

Angiopoietin-Like Proteins 2 and 3 in Children and Adolescents with Obesity and Their Relationship with Hypertension and Metabolic Syndrome

“…ANGPTL2 may contribute to adipose tissue remodeling by promoting angiogenesis, macrophage recruitment, and extracellular matrix transformation [ 13 ]. ANGPTL2 has not been previously studied in obese children; however, elevated level of ANGPTL2 has been reported in obese women, which was consistent with our findings [ 17 ]. Maintaining adipocytes under conditions similar to the microenvironment of obese adipose tissue induced ANGPTL2 gene expression and secretion [ 17 ].…”

“…ANGPTL2 has not been previously studied in obese children; however, elevated level of ANGPTL2 has been reported in obese women, which was consistent with our findings [ 17 ]. Maintaining adipocytes under conditions similar to the microenvironment of obese adipose tissue induced ANGPTL2 gene expression and secretion [ 17 ]. Enhanced expression of ANGPTL2 seems to be a response to the increased inflammation that accompanies obesity, such that TNF α and TGF β that are increased in obesity directly increase gene expression of ANGPTL2 [ 31 ].…”

“…In vivo, elevated serum ANGPTL2 levels positively associate with the development of type 2 diabetes [ 16 ]. Systemic levels of this protein are increased in the obese patients compared to healthy controls and are positively correlated with body mass index and insulin resistance [ 17 ].…”

Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?

“…Under normal conditions, ANGPTL2-mediated expression contributes to angiogenesis and tissue damage repair, whereas overexpression promotes chronic inflammation [17][18][19]. In obese women with insulin resistance, ANGPTL2 production by adipocytes was shown to upregulate proinflammatory cytokine production in macrophages, in turn increasing adipose tissue inflammation, systemic insulin resistance and hyperinsulinaemia [20]. Thus, ANGPTL2 provides a link between the metabolic syndrome, NAFLD and ASCVD.…”

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

“…ANGPTL2 is a recently identified adipokine that shares structural similarity with angiopoietin and found elevated in the serum of obese diabetic women . ANGPTL2 production was shown to be stimulated in human adipocyte culture exposed to stresses that mimic adipose tissue in obesity, and therefore the adipokine is assumed to promulgate adipose tissue inflammation and insulin resistance . Indeed, TNF‐α was found to induce ANGPTL2 expression in adipocytes in vitro .…”