Inflammatory Protein May Provide Link Between Obesity and Severe Pancreatitis

The pancreas is a large gland located in the abdomen adjacent to the stomach. It plays an important role in the digestion and utilization of food. Digestive enzymes secreted by the pancreas help to break down the carbohydrates, fats and proteins in foods, allowing them to be absorbed by the small intestine (first portion of the bowel). The pancreas also releases insulin into the bloodstream, regulating blood sugar levels and facilitating the use of blood glucose for energy.

Pancreatitis is a condition involving inflammation of the pancreas

Acute pancreatitis refers to a sudden inflammation (tissue reaction) of the pancreas. This can have a number of causes, including chronic heavy alcohol use and the presence of gallstones. In 10 to 15% of cases, the cause may not be identified.

Symptoms of pancreatitis include severe pain in the upper abdomen, nausea and vomiting, and fever. Acute pancreatitis is a life-threatening condition, which requires immediate medical attention and hospitalization. Approximately 80% of patients are diagnosed with mild pancreatitis, while 20% suffer from severe pancreatitis. Severe pancreatitis involves both local (involving the pancreas) and systemic (involving the body as a whole) complications. Local complications include pancreatic necrosis, or destruction of the pancreatic tissue, severe infection, and hemorrhage (bleeding) from adjacent blood vessels. Systemic complications include kidney failure, respiratory failure and death.

Obesity worsens the severity of acute pancreatitis

Worldwide obesity has more than doubled since 1980. It is estimated that more than 1.4 billion adults are overweight, and more than 500 million are obese. Obesity is defined as a body mass index (BMI) greater than 30. BMI is calculated as weight in kilograms divided by the square of height in meters (kg/m2); weight-for-height BMI tables and calculators are also widely available.

Obesity is a risk factor in many chronic illnesses including hypertension and diabetes. Scientists are only recently beginning to understand the links between obesity and more acute illnesses, including pancreatitis. An analysis of multiple medical studies (meta-analysis) reveals that obese patients are 4 times more likely to suffer from local complications of acute pancreatitis than normal weight patients. Obese patients are also twice as likely to suffer from severe complications and death related to acute pancreatitis.

Obesity and local complications of pancreatitis

Obese patients have a greater number of fat cells interspersed with the normal functioning cells of the pancreas. In the setting of acute inflammation, some of these fat cells are destroyed and their contents are released into the surrounding pancreatic tissue. Investigators believe that these fat cells contain large amounts of compounds known as unsaturated fatty acids. In laboratory studies and animal models, these unsaturated fatty acids have the ability to kill pancreatic cells, and to damage the lungs and kidneys. This may explain why there is a much greater rate of pancreatic necrosis (destruction) in obese patients. This destruction can result in the loss of pancreatic function, as well as the accumulation of destructive pancreatic enzymes outside of the pancreas (called a pseudocyst). Necrotic pancreatic tissue can also give rise to serious infections called abscesses, collections of pus and debris deep within the abdomen that usually need to be treated surgically.

The role of adipokines in pancreatitis

Researchers believe that obesity is associated with a chronic low grade inflammatory state, such that the body’s immune system is always activated. This results in high levels of fat-associated cytokines, or adipokines. Adipokines are cell-to-cell signaling proteins responsible for the damaging immune response that leads to severe inflammation and tissue destruction.

One of these adipokines is called interleukin-6 (IL-6). Scientists from the Universities of Illinois and California have discovered that IL-6 plays a pivotal role in the prolongation of acute pancreatitis. Using an animal model, investigators demonstrated that obese mice developed more severe pancreatitis than normal weight mice. They were then able to demonstrate that obese mice unable to produce IL-6 recovered much more quickly from acute pancreatitis than obese mice that did produce IL-6.

This research suggests that future drugs targeting adipokines, particularly IL-6, may be an important tool for decreasing the risk of severe complications in obese patients with acute pancreatitis. This could be an important adjunct to current nonspecific supportive therapy for pancreatitis, which comprises only intravenous fluids and pain medications.

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