By Paul Ian Cross, PhD — Fact checked by Alexandra Sanfins, Ph.D.
Obesity leads to significant changes in adipose (fat) tissue metabolism, harms the pancreas, impairs insulin sensitivity, and eventually causes hyperglycemia (high blood sugar), which is the foundation of type 2 diabetes.
Additionally, it triggers a low-grade inflammatory reaction throughout the body, which promotes the infiltration of white blood cells into numerous tissues, including fat deposits located deep within the body that surround organs, such as the liver and gut — called visceral adipose tissue — and the peritoneal cavity, a delicate membrane that encloses the gut.
According to a new study, published in Clinical and Experimental Immunology, the adiponectin-PEPITEM pathway provides a link between obesity, the accompanying low-grade inflammatory response, and modifications in the pancreas that occur prior to the onset of diabetes.
Using a mouse model of obesity, the researchers administered the peptide PEPITEM using a slow-release pump, to see if it could prevent or perhaps even reverse the impacts of a high-fat diet on the pancreas.
The researchers found that administering PEPITEM to mice that were following a high-fat diet resulted in a significant reduction in the enlargement of insulin-producing cells in the pancreas and the number of white blood cells in the visceral adipose tissue and peritoneal cavity when compared to the control group.
The scientists also investigated whether PEPITEM could reverse the changes caused by obesity by administering a high-fat diet to the animals before treating them with PEPITEM.
Lead researcher Dr. Helen McGettrick, from the University of Birmingham’s Institute of Inflammation and Ageing, explained the key findings to Medical News Today.
“Using an animal model of obesity, we showed that a small peptide called PEPITEM can limit the number of immune cells entering into a variety of tissues across the body and it also reduces the size of insulin-producing cells in the pancreas,” she told us.
“Immune cell movement into tissues is an important protective response to infection and tissue damage. However, uncontrolled immune cell migration underpins tissue damage in a number of chronic diseases including obesity, type 2 diabetes, and cardiovascular disease. In type 2 diabetes the insulin-producing cells of the pancreas increase in size and number as they become damaged.”
– Dr. Helen McGettrick
“These preclinical data suggest that PEPITEM may offer a new therapy that could halt the onset of type 2 diabetes in obese individuals,” Dr. McGettrick added.
Dr. McGettrick noted that “in lean people, fat tissues work closely with the body’s hormones to maintain tissues in a healthy, anti-inflammatory state. In obesity, this is lost, and the fat takes on a different personality that drives inflammation throughout the body.”
For this reason, she explained, people with obesity have “a greater risk of developing other diseases, such as type 2 diabetes, atherosclerosis, and fatty liver disease.”
“There is an urgent need to find new drugs for people at risk of developing these diseases, whilst they strive to reduce their weight through diet and exercise,” said Dr. McGettrick.
According to her, “PEPITEM may be the answer, offering a new type of drug that can halt the onset and progression of obesity-related conditions.”
Dr. Edwin Bosa-Osorio, from Community Health of South Florida, not involved in this research, agreed, telling MNT that “obesity-related health issues are a big problem in our society, so finding new ways of addressing these issues [is] worth pursuing.”
“People who have diabetes or obesity often experience complications with the body’s inflammatory processes that include insulin resistance, cardiovascular problems, and other adverse effects. Inflammation in the body is mediated through T cells and this small bioprotein, PEPITEM, which is being studied, functions as an anti-inflammatory by modulating the movement of these T cells, leading to less problems with insulin resistance and other problems caused by obesity.”
– Dr. Edwin Bosa-Osorio
Nicole Anziani, registered dietitian, certified diabetes care and education specialist, and senior clinical manager for Cecelia Health, who was not involved in the study, noted that this could “potentially be a useful additional tool for patients regarding the prevention or treatment of type 2 diabetes, especially as related to the decrease in enlargement of the beta cells.”
“Of note, the mice in the study were fed a high-fat diet, either prior to the administration of PEPITEM or during its administration, to investigate PEPITEM’s effects on obesity,” Anziani said.
However, Anziani highlighted that it is important to understand that obesity is of multifactorial etiology — meaning it can be caused by multiple factors — and not necessarily caused by a high-fat diet.
Anziani also highlighted that obesity was not “solely a biochemical phenomenon.”
“While it’s wonderful to have more available options to help patients with the biochemical aspects of obesity and preventing systemic inflammation, especially when there may already be pancreatic damage present, it’s also essential to acknowledge the behavioral and social aspects related to the development of obesity and other related ailments,” Anziani told us.
“While this therapeutic approach is being investigated to get to the root cause of obesity-related conditions, further research into the association between inflammation and obesity is still needed to fully understand these mechanisms,” she added.
Dr. Bosa-Osario agreed, noting that “while more studies would be required, the findings appear promising.”
He also added that PEPITEM may be a good therapeutic target for other reasons. “While the body can create a similar bioprotein to PEPITEM, PEPITEM can be produced in a lab, then given to people. That’s exciting,” he said.
“If safely administered, it could prove a significant benefit to people suffering from obesity who experience insulin resistance and other inflammatory issues, which PEPITEM can reverse, allowing for insulin to function more efficiently, thereby reducing the need for other agents we now use to address these health issues.”
– Dr. Edwin Bosa-Osorio
This article originally appeared here and was republished with permission.