Abstract
ABSTRACT Secreted frizzled-related protein (SFRP) 4 is an extracellular antagonist of Wnt signalling that regulates adipogenesis, and is highly in the visceral adipose tissue of obese individuals. However, it is still unclear how exactly SFRP4 regulates the secretion of adipokines in the adipose tissue in vivo, an event that is closely related to the pathogenesis of obesity and insulin resistance. In this study, we generated transgenic (Tg) mice overexpressing SFRP4 in the liver and investigated SFRP4 role in adipokine secretion in mice on a regular normal diet. In Tg mice, SFRP4 protein was overexpressed in the liver, as compared to wild-type littermates (non-Tg), and released into the blood. Moreover, the size of adipocytes was smaller in the visceral adipose tissue of Tg mice compared to controls. Additionally, SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. However, there was no difference in body weight or body composition between Tg and non-Tg mice. In summary, our data showed that SFRP4 overexpression altered adipocyte size and adipokine secretion, possibly affecting adipocyte differentiation, obesity, and glucose metabolism.
Highlights
Obesity is a health risk factor, closely associated with chronic non-communicable diseases such as metabolic syndrome, type 2 diabetes, and hypertension [1]
The results showed that in WT mice, Secreted frizzled-related protein 4 (SFRP4) expression was highest in the inguinal white adipose tissue (ig WAT), followed by the liver and epididymal white adipose tissue (epi WAT) (Figure 1(b))
The observed differences in SFRP4 expression between visc eral and subcutaneous adipose tissue, as well as in plasma SFRP4 level between WT and ob/ob mice, sug gested that SFRP4 played an important role in adipo genesis and adipocyte differentiation
Summary
Obesity is a health risk factor, closely associated with chronic non-communicable diseases such as metabolic syndrome, type 2 diabetes, and hypertension [1]. SFRP4 is expressed in adipo cytes, as well as in various tissues including pancreas, heart, bone, and uterus, and is involved in multiple patho physiological processes including fibrosis, angiogenesis, apoptosis, malignancy, adipogenic differentiation, and bone metabolism [13,14,15,16,17,18,19]. SFRP4 is overexpressed in obese individuals and patients with type 2 diabetes [22,23]. SFRP4 is overexpressed in the islets of patients with type 2 diabetes and is considered a marker of early beta cell dysfunction [24]. SFRP4 pro motes the differentiation of human adipose tissue-derived mesenchymal stem cells into mature adipocytes [19]
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