Abstract
Obesity is an increasingly serious epidemic worldwide characterized by an increase in the number and size of adipocytes. Adipose tissue maintains the balance between lipid storage and energy utilization. Therefore, adipose metabolism is of great significance for the prevention, treatment and intervention of obesity. Asprosin, a novel adipokine, is a circulating hormone mainly secreted by white adipose tissue. Previous studies have shown that asprosin plays a role in fasting-induced homeostasis, insulin resistance, and glucose tolerance. However, whether it can regulate the metabolism of adipose tissue itself has not been studied. This study intended to examine the roles and potential mechanisms of asprosin in adipose regulation. We first demonstrated that the expression level of asprosin was significantly downregulated in subcutaneous white adipose tissue (scWAT) of high-fat diet (HFD)-fed or cold-stimulated mice. Overexpression of asprosin in scWAT reduced heat production, decreased expression of the browning marker uncoupling protein 1 (UCP1) and other browning-related genes, along with upregulation of adipogenic gene expression. Mechanistically, we found that Nrf2 was activated upon cold exposure, but this activation was suppressed after asprosin overexpression. In primary cultured adipocytes, adenovirusmediated asprosin overexpression inhibited adipose browning and aggravated lipid deposition, while Nrf2 agonist oltipraz could reverse these changes. Our findings suggest that novel adipokine asprosin negatively regulated browning and elevate lipid deposition in adipose tissue via a Nrf2-mediated mechanism. Asprosin may be a promising target for the prevention and treatment of obesity and other metabolic diseases.
Highlights
Obesity and obesity-related disorders such as type 2 diabetes are steadily increasing worldwide with the improvement of people’s living standards and unhealthy lifestyle (Mohammed et al 2018)
We analyzed asprosin expression in subcutaneous white adipose tissue from mice maintained at room temperature (RT) or in a cold environment (4°C) and found that the expression of asprosin was decreased, at both mRNA and protein levels (Fig. 1B and C)
These findings indicated that the novel adipokine asprosin may play an important role in adipose energy production and conversion
Summary
Obesity and obesity-related disorders such as type 2 diabetes are steadily increasing worldwide with the improvement of people’s living standards and unhealthy lifestyle (Mohammed et al 2018). Endocrinology and adipogenesis increasing energy expenditure in key metabolic organs, such as adipose tissue. Adipose tissue can be further divided into white (WAT) and brown (BAT) adipose tissue, which are distinct in form and function and have different metabolic characteristics (Bartelt & Heeren 2014). When exposed to certain environmental stimuli (such as cold exposure), adipocytes in white adipose tissue convert to a brownish phenotype, which is called white adipose tissue browning (Wang & Seale 2016). The browned white adipocytes begin to express uncoupling protein-1 (UCP1), a specific marker of brown adipose tissue, making white adipose tissue more likely to generate heat and increase the body’s energy consumption. Browning of white adipose tissue is currently considered as a new approach to weight loss, insulin sensitivity and glucose tolerance, with potential therapeutic effects in the treatment of obesity and cardiovascular diseases
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