This protein may target major cause of obesity, mouse study finds

PEPITEM prevented or reversed the effects of a high-fat diet on the pancreas, researchers found.

ISLAMABAD, (Online) - A naturally-occurring small protein, or peptide, could provide a new way to reduce the risk of type 2 diabetes, fatty liver and other obesity-related diseases, suggests a recent study in mice.

When researchers administered this peptide, known as PEPITEM, to mice, it prevented or reversed the effects of a high-fat diet on the pancreas, researchers found.

Mice who received this peptide also saw a reduction in the enlargement of insulin-producing cells in the pancreas, and a reduction in the migration of immune cells into certain 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,” study author Helen McGettrick, PhD, an experimental biologist at University of Birmingham’s Institute of Inflammation and Ageing in the UK, said in a statement.

However, more research is needed — including clinical trials in people — before scientists will know if this might be an effective treatment for obesity-related diseases. Small protein impacts some effects of obesity

The peptide used in this study plays a role in the adiponectin - PEPITEM pathway, which is involved in controlling the onset and severity of auto-immune and chronic inflammatory diseases.

Obesity can have a number of effects throughout the body, including changing metabolism in adipose (fat) tissue, damaging the pancreas, reducing insulin sensitivity, and eventually leading to the high glucose levels that occur with type 2 diabetes.

But it also causes a low-level inflammatory response, with a movement of white blood cells into adipose tissue surrounding organs such as the liver and gut (visceral adipose tissue), and into the space within the abdomen that contains the intestines, stomach the liver (peritoneal cavity).

In the new study, published March 9 in the journal Clinical and Experimental Immunology, researchers fed mice a high-fat diet, with some of the mice also given PEPITEM.

Compared to mice who did not receive the peptide, those that did, had a reduction in the enlargement of insulin-producing beta cells in the pancreas. They also saw a decrease in the number of white blood cells in the visceral adipose tissue and peritoneal cavity.

“These results show us that PEPITEM can both prevent and reverse the impact that obesity has on metabolism,” study author Asif Iqbal, PhD, an associate professor at the University of Birmingham’s Institute of Cardiovascular Sciences, said in the release.

“The next stage is to translate these exciting results into therapeutics that can be used in humans,” he said.

Dr. Christoph Buettner, an endocrinologist and professor of medicine at the Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, told Healthline that scientists have known for many years that obesity and diabetes are associated with increased inflammation.

However, “while in mice several drugs that specifically lower inflammation have been shown to also reduce obesity and diabetes, in humans — where obesity is also often associated with inflammation — the data are much less clear,” he said.

Results from the current study suggest that PEPITEM may have a positive impact on some of the downstream effects of obesity — in particular, reducing enlargement of the insulin-producing beta cells and reducing white blood cells in certain tissues.

But mice that received PEPITEM still gained weight on a high-fat diet. There was also “no effect on fasting glucose tolerance or insulin resistance,” the researchers wrote — both of these are impacted in people with type 2 diabetes.

“To me, that suggests that this is an anti-inflammatory treatment that is unlikely to have a meaningful effect on either obesity or high blood sugar,” said Buettner.

Effective weight loss drugs already approved

While more research is needed to know if PEPITEM will play a role in treatment for obesity-related conditions such as type 2 diabetes, some drugs have already been approved to treat obesity.

This includes semaglutide (brand names Ozempic, Wegovy and Rybelsus), which is a type of drug known as a GLP-1 agonist. In clinical trials, people who took semaglutide lost weight — in one trial, up to 14.9% of their starting weight — as well as saw a reduction in inflammation.

However, “that does not prove that [these drugs] work by reducing inflammation,” said Buettner, “as these are not drugs that are considered primarily anti-inflammatory.”

Instead, “they work in the brain to reduce appetite and balance the autonomic nervous system,” he said.