by Kumamoto University

The study found that SerpinA1 helps activate mitochondria in both white and brown fat cells, promoting the “browning” of fat tissue, which boosts energy burning and reduces fat accumulation. Credit: Kumamoto University

Researchers from Kumamoto University have identified a liver-derived protein, serine protease inhibitor A1 (SerpinA1), as a key regulator in combating obesity and enhancing glucose metabolism. This study, published in Nature Communications, sheds light on how activating brown adipose tissue (BAT) could pave the way for innovative treatments for diabetes and metabolic disorders.

While white adipose tissue (WAT) stores excess energy, brown adipose tissue (BAT) burns it, generating heat. As people age, BAT diminishes, increasing obesity risk. SerpinA1, a hepatokine secreted by the liver, has been shown to reverse this process by promoting the browning of WAT and activating BAT.

In their study, the team led by Assistant Professor Masaji Sakaguchi demonstrated that SerpinA1 significantly increases the expression of uncoupling protein 1 (UCP1), a protein critical for thermogenesis. Transgenic mice overexpressing SerpinA1 exhibited increased energy expenditure, improved glucose tolerance, and resistance to obesity, even on a high-fat diet. Conversely, mice lacking SerpinA1 displayed reduced mitochondrial activity, leading to obesity and insulin resistance.

SerpinA1 interacts with the cell surface molecule EphB2 to trigger pathways that enhance UCP1 expression and mitochondrial activity in adipocytes. This finding reveals a novel signaling mechanism that operates independently of traditional β-adrenergic pathways.

This discovery highlights a potential therapeutic pathway for treating obesity and type 2 diabetes by stimulating the body’s natural ability to burn fat. “Our findings suggest that boosting SerpinA1 levels could offer a new approach to managing metabolic diseases,” said Assistant Professor Sakaguchi.

The research team aims to develop clinical applications based on this discovery, with hopes of advancing towards innovative treatments for metabolic syndrome and related disorders.

More information: Shota Okagawa et al, Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression, Nature Communications (2024). DOI: 10.1038/s41467-024-53835-9

Journal information:Nature Communications

Provided by Kumamoto University

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