Naturally Occurring Peptide May Combat Root Cause of Obesity-Related Conditions

A brand new study published in Clinical and Experimental Immunology shows that a naturally occurring peptide called PEPITEM could offer a revolutionary strategy for mitigating the risk of type 2 diabetes and other obesity-related conditions such as fatty liver.

Using an animal model of obesity, the University of Birmingham researchers explored the potential of PEPITEM administered via a slow-release pump to counteract or reverse the effects of a high-fat diet on the pancreas. The incredible findings demonstrated that infusing PEPITEM effectively reduced the expansion of insulin-producing cells in the pancreas and lowered the migration of immune cells into different tissues.

“We have found a new therapeutic approach that could provide new drugs to tackle the root cause of obesity-related conditions by preventing the damage caused by systemic inflammation,” said lead researcher Helen McGettrick, PhD.

Researchers from Birmingham first discovered PEPITEM in 2015 and described its involvement in the adiponectin-PEPITEM pathway, which plays a crucial role in regulating the development and severity of autoimmune and chronic inflammatory disorders.

Obesity causes significant and complex metabolic changes in adipose tissue, impairs pancreatic function, reduces insulin sensitivity, and culminates in hyperglycemia, the hallmark of type 2 diabetes. It also promotes a systemic low-grade inflammatory response, attracting white blood cells to multiple tissues, including the visceral adipose tissue deep inside the abdomen around the organs and the peritoneal cavity which surrounds the gut.

This latest research shows that the adiponectin-PEPITEM pathway is a link between obesity, the low-level inflammatory response that is driven by it, and changes in the pancreas that precede diabetes.

The groundbreaking findings demonstrate that administering PEPITEM significantly decreased the expansion of beta cells that produce insulin in the pancreas and lowered the number of white blood cells in the visceral adipose tissue and peritoneal cavity in mice receiving a high-fat diet, in comparison to control groups.

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The researchers also fed the animals a high-fat diet prior to treating them with PEPITEM to study its potential to reverse the changes brought on by obesity and were excited by the results.  “Until now we have understood very little about how the inflammation that accompanies obesity drives pathology,” said co-lead researcher Asif Iqbal, PhD. These results show us that PEPITEM can both prevent and reverse the impact that obesity has on metabolism. The next stage is to translate these exciting results into therapeutics that can be used in humans.”

“PEPITEM is a naturally occurring peptide,” said Professor Ed Rainger from Birmingham’s Institute of Cardiovascular Sciences who led the team that first identified it.  “We have already shown it has effects on several organs and now for the first time, we have shown that PEPITEM is effective in a model of a disease process that is not driven by the immune system alone.”

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