USask researchers identify promising protein candidate for treatment of metabolic diseases – News

The researchers' findings, recently published in Nature Communications Biology, highlight their discovery of the hypolipidemic effects of nesfatin-1-like peptide (NLP). This newly identified peptide (or small protein) is a close relative of nesfatin-1 (NESF-1), which regulates food intake and body weight.

“We found that NESF-1 and NLP reduce lipid (fat) accumulation in human liver cells,” said research team member Dr. Suraj Unniappan (PhD), Centennial Enhancement Chair. in comparative endocrinology from the university and professor at the Western College of Veterinary Medicine (WCVM). The collaborative study involved researchers from WCVM and the USask College of Medicine.

While the lipid-lowering effect of nesfatin-1 had previously been reported, Unniappan said that identifying NLP and understanding its lipid-lowering abilities in human cells represents new advances in the field of endocrinology.

“We are a long way from being able to bring these results to the bedside,” Unniappan said. “But we now have additional multiple targets that could be explored for lipid disease treatment and therapeutic advancements.”

The research team's discovery is encouraging news, as there is a lack of new treatments for many metabolic diseases, including non-alcoholic fatty liver disease (recently renamed metabolic dysfunction-associated steatotic liver disease or MAFLD), which affects approximately 20 percent of Canadians. A hormone-based drug was approved in the United States in March 2024, but so far, no drug is currently available in Canada exclusively to treat this condition.

Typical treatment plans for humans and animals with metabolic disease usually consist of changes in diet and exercise to gradually reduce body weight and reduce fat accumulation.

Unniappan and his research team have been at the forefront of nesfatin-1 research. Discovered in 2006 by a group of researchers in Japan, nesfatin-1 was initially recognized for its ability to suppress food intake.

The USask team went further than previous studies and successfully verified that genetic disruption of NLP led to changes in genes involved in lipid metabolism in mice.

“We found that if you disrupt the gene that is the source of this naturally occurring protein (NLP) in these animals, it actually leads to changes in genes associated with lipid metabolism,” Unniappan said.

The discovery of such findings – that administration of NLP reduces lipid levels, while disruption of its production alters lipid metabolism – reinforces its central role in metabolic regulation.

Unniappan and Dr. Atefeh Nasri (PhD), who completed her doctoral program at USask in 2023 and is now a postdoctoral fellow at Dalhousie University, collaborated with Dr. Scott Widenmaier (PhD), assistant professor of anatomy, physiology and pharmacology. , and expert in metabolic diseases at USask College of Medicine. The fourth member of the team was undergraduate student Mateh Kowaluk.

Unniappan hopes this new research can pave the way for further exploration of treatment options. He plans to work with collaborators to expand this research into more complex animal models, including rodents, and eventually study larger animals, like cats and dogs. Like humans, these species also suffer from obesity and associated metabolic disorders.

“It's wonderful to know that the same peptide can produce so many meritorious health effects, which combined have the potential to help human and animal patients,” Unniappan said.

This research was funded by the Canadian Institutes of Health Research (CIHR) and the USask Centennial Enhancement Chair in Comparative Endocrinology.