Monday, November 29, 1999

Protein that modulates metabolic dysfunction in obesity identified

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Washington, June 18 (ANI): A new American study has identified the protein that modulates metabolic dysfunction in obesity.The findings of the research, conducted by Boston University School of Medicine (BUSM), have appeared online in the journal Science.The researchers discovered that Sfrp5 (secreted frizzled-related protein 5) is an anti-inflammatory adipokine whose expression is disrupted in animal models of obesity and type 2 diabetes.Obesity is a predisposing factor for metabolic disorders such as type 2 diabetes, 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 tumour necrosis factor (TNF) a, 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.Senior author Kenneth Walsh, director of the Whitaker Cardiovascular Institute at BUSM, said: "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."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.Walsh said: "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." (ANI)

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