A peptide called PEPITEM could provide a new approach to reducing the risk of type 2 diabetes and other obesity-related diseases, such as hepatic steatosis (fatty liver), according to research based on animal studies published today in Clinical & Experimental Immunology.
“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 senior author Helen MCGettrick of University of Birmingham’s Institute of Inflammation and Aging.
The researchers used a mouse model of obesity to investigate whether the immunopeptide PEPITEM, delivered by a slow-release pump, could prevent or reverse the effects of a high fat diet on the pancreas.
They found that administration of the compound significantly reduced the enlargement of insulin-producing cells in the pancreas and slowed immune cell migration into other tissues.
It’s projected that one billion adults and 206 million children worldwide will be clinically obese by 2025. The economic impact of these diseases was estimated to be 2.19% of global gross domestic product in 2019.
Obesity causes complex and dramatic changes in metabolism in adipose (fat) tissue, damage to the pancreas, reduced insulin sensitivity and eventually the hyperglycemia that underpins type 2 diabetes.
It also leads to a low-level inflammatory response across the body, encouraging white blood cells to enter into many tissues including the visceral adipose tissue (fat stored deep inside the body wrapped around the organs, including the liver and gut) and peritoneal cavity (a thin membrane that encompasses the gut).
This research from the Birmingham team shows that the adiponectin-PEPITEM pathway connects obesity, the low-level inflammatory response that is driven by it, and changes in the pancreas that precede diabetes.
The study results showed that dosing with PEPITEM while the mice were on a high fat diet significantly reduced the enlargement of insulin-producing beta cells in the pancreas and the number of white blood cells in the visceral adipose tissue and peritoneal cavity, compared to controls.
The researchers also looked at the potential of PEPITEM to reverse the changes brought on by obesity, by feeding the animals a high fat diet prior to treating with PEPITEM, and also saw positive results.
“Until now we have understood very little about how the inflammation that accompanies obesity drives pathology. 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,” said co-author Asif Iqbal from the University of Birmingham’s Institute of Cardiovascular Sciences.
PEPITEM was first identified in 2015 by Birmingham researchers who described its role in the adiponectin-PEPITEM pathway, which is involved in controlling the onset and severity of autoimmune and chronic inflammatory diseases.
Professor Ed Rainger from Birmingham’s Institute of Cardiovascular Sciences led the team that made that initial discovery.
Rainger said, “PEPITEM is a naturally occurring peptide. 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.”