Researchers identify protein that modulates metabolic dysfunction in obesity

Jun 17, 2010

Researchers from Boston University School of Medicine (BUSM) have discovered that Sfrp5, which refers to secreted frizzled-related protein 5, is an anti-inflammatory adipokine whose expression is disrupted in animal models of obesity and type 2 diabetes. The findings, which currently appear on-line in Science, may provide a new way of targeting metabolic disease, specifically obesity.

Obesity is a predisposing factor for metabolic disorders such as type 2 , which is often associated with a low-grade inflammatory state in adipose tissue. Adipose tissue secretes a variety of cytokines, referred to as adipokines. Most adipokines, such as (TNF) α, interleukin (IL)-6 and leptin, are pro-inflammatory. One prominent exception is adiponectin, an anti-inflammatory adipokine that promotes insulin sensitization and protects cardiovascular tissue from ischemic injury.

According to the researchers, because adipokine dysregulation can contribute to the pathogenesis of obesity-linked disorders, they sought to identify new adipokines by comparing the gene expression profile of adipose tissue from lean mice with that from obese mice on a high calorie diet.

"Our study shows that Sfrp5 is secreted by adipocytes and that it controls the microenvironment of white adipose tissue under conditions of obesity-induced metabolic stress. Whereas Sfrp5 deficient mice do not express a detectable phenotype when fed a normal diet, these animals displayed aggravated fat pad inflammation and systemic metabolic dysfunction when fed a high calorie diet," explained senior author Kenneth Walsh, PhD, director of the Whitaker Cardiovascular Institute at BUSM. Conversely, the BUSM researchers found the administration of Sfrp5 to models of obese and diabetic mice improved metabolic function and reduced adipose tissue inflammation.

The researchers propose that Sfrp5 neutralizes noncanonical JNK activation by Wnt5a in macrophages and adipocytes via paracrine and autocrine mechanisms, respectively. "The JNK signaling pathway in adipocytes and macrophages has emerged as an important mediator of adipose tissue inflammation that affects systemic metabolism. Thus, the Sfrp5-JNK1 regulatory axis in fat represents a potential target for the control of obesity-linked abnormalities in glucose homeostasis," added Walsh.

Explore further: Molecule enhances copper's lethal punch against microbes

Related Stories

Inflammation in body fat is not only pernicious

Mar 25, 2010

It has been a common opinion that inflammation in adipose tissue may cause insulin resistance, and thereby type 2 diabetes. However, recent research from the Swedish medical university Karolinska Institutet, published in ...

Control of blood vessels a possible weapon against obesity

Jan 07, 2009

Mice exposed to low temperatures develop more blood vessels in their adipose tissue and metabolise body fat more quickly, according to a new study from Karolinska Institutet. Scientists now hope to learn how to control blood ...

Researchers identify how stressed fat tissue malfunctions

Jul 14, 2009

Ben-Gurion University of the Negev (BGU) researchers, in a collaboration with colleagues from the University of Leipzig, Germany, have identified a signaling pathway that is operational in intra-abdominal fat, the fat depot ...

Recommended for you

Breakthrough in understanding of important blood protein

17 hours ago

The human body contains a unique protein that has the unusual property of destroying itself after a few hours of existence - it must therefore be continually recreated and is no stable protein. The protein, ...

User comments : 0