Obesity caused by a high-fat Western diet damages the pancreas, affecting insulin production and blood sugar control even after dietary changes and weight is lost. The new research suggests that early intervention is needed to stop obesity from causing permanent pancreatic damage.
While the term “Western diet” is not strictly a euphemism for junk food, it’s frequently categorized by diets high in processed foods, sugary drinks, and other items that attract the junk food label. And, research has made us aware of the negative impact that consuming this type of food can have on health, particularly in the long term.
In a new study led by Sweden’s Karolinska Institutet (KI), researchers examined the effect that obesity caused by consuming a Western diet has on the pancreas. They particularly focused on the tiny blood vessels of the pancreatic islets, clusters of cells that produce hormones, including insulin, that regulate blood glucose metabolism and maintain glucose balance.
“This study reveals that islet vessel dysfunction is a hidden but significant contributor to glucose intolerance in obesity, and that these defects may become permanent if not addressed early,” said the study’s senior author, Professor Per-Olof Berggren, from KI’s Department of Molecular Medicine and Surgery.
Glucose intolerance is when blood sugar levels are higher than normal but not high enough to be diagnosed as diabetes. It is a significant sign of increased risk for type 2 diabetes.
The researchers fed mice a high-fat Western diet (WD) to mimic obesity and studied the changes that occurred in the pancreatic islet blood vessels over time. After 12 weeks, the mice had gained weight and developed glucose intolerance. Their islet blood vessels became structurally abnormal, developing thicker walls and reducing blood flow. The vessels also stopped responding to vascular endothelial growth factor A (VEGF-A), a protein that plays a crucial role in the development of new blood vessels and the growth and survival of existing ones.
While the islet cells still produced insulin, the researchers noted that damaged vessels slowed down how quickly it got into the bloodstream, which contributed to high blood sugar levels. Importantly, even when the mice were switched back to a healthy diet for 24 weeks, many of the problems persisted. The blood vessels still responded poorly to VEGF-A, their structure remained abnormal, and insulin release was still delayed.
“This desensitization hindered the proper regulation of islet blood flow and vessel barrier function, delaying the release of insulin into the bloodstream during glucose challenges,” said lead author Dr Yan Xiong, from the same department at KI.
The researchers identified a molecule, atypical protein kinase C (aPKC), that became overactive in response to the high-fat and high-sugar intake characteristic of a WD. This overactivity blocked VEGF-A signaling, preventing blood vessels from properly maintaining themselves.
The study had limitations. First, only male mice were used, so they’re unable to tell whether the same effects occurred in females. Further, aging can affect blood vessels. Because the mice were studied over almost a year, it’s hard to tell how much damage was due to aging and how much was due to diet. While the researchers identified aPKC as a key player, its upstream triggers weren’t fully mapped. And, perhaps most importantly, while mice are a good research model, the results seen may not fully apply to humans.
Nonetheless, the study’s findings suggest that obesity causes lasting damage to the blood vessels in the pancreatic islets by making them unresponsive to the protein that is crucial for maintaining vessel health. Given that the effect on insulin release was unchanged even after the diet was altered and weight was lost, it indicates that early intervention is crucial, as the damage can become permanent and contribute to diabetes.
“Understanding islet vessel pathology opens up new therapeutic opportunities aimed at preserving islet vascular health in metabolic diseases,” Berggren said.
The study was published in The Journal of Clinical Investigation.
Source: Karolinska Institutet
