University Times

Fat’s role in pancreatitis complications studied

The toxic byproducts produced by the breakdown of unsaturated fats lead to a higher likelihood of severe inflammation, cell death and multi-system organ failure among acute pancreatitis patients who are obese, say researchers at the School of Medicine. Their findings, published online in Science Translational Medicine, provide new insight into how fat can induce complications after sudden inflammatory, non-infectious illnesses.

Doctors have observed that obese people are at greater risk for adverse outcomes after trauma, severe burns, critical illnesses and acute pancreatitis, which is an inflammatory condition of the pancreas typically brought on by gallstones and alcohol, said senior author Vijay Singh, a faculty member in the Department of Medicine’s Division of Gastroenterology, Hepatology and Nutrition.

“The mortality rate among patients with severe acute pancreatitis is 40-50 percent when kidney failure and respiratory failure develop,” he said. “Our findings indicate that the breakdown of unsaturated fat in acute inflammatory conditions can lead to tissue damage throughout the body.”

Singh’s team examined pancreas tissue from 24 patients who died with acute pancreatitis and compared them to 50 people who died of other causes. They found that the diseased pancreases of obese patients, meaning those with a body mass index of 30 or more, contained more fat cells, and confirmed the presence of fat from CT imaging scans from the patients taken before their deaths. Autopsy tissue showed also that there was more pancreatic cell death in the areas around fat cell destruction.

Pancreatic fluids from six obese patients with severe acute pancreatitis who had surgical procedures to remove dead tissue revealed high amounts of unsaturated fatty acids, produced from the breakdown of unsaturated fat, than saturated fatty acids. When the researchers combined healthy pancreatic cells with the unsaturated fatty acids in a test tube, the pancreatic cells died.

Then, they induced pancreatitis in obese mice and found that like the human patients, they had high amounts of fat in their pancreases. The fat in obese mice was mostly unsaturated. Kidneys of the mice with pancreatitis were damaged and contained fat deposits, an unexpected finding supported by studies in human autopsy tissue. Infusing unsaturated fatty acids into the bloodstream of the animals leads to lung injury akin to the problems seen in human patients, while administration of saturated fatty acids does not.

“Now that we better understand why these complications arise, we might be able to prevent them and reduce deaths,” Singh said. “We must find ways to stop this toxic process.”

He and his team are studying ways to prevent the generation of unsaturated fatty acids in obese rodents to see what happens when they develop acute pancreatitis.

Pitt researchers included Teresa McHale, Sarah Navina and Larry Nichols, pathology; Jaideep Behari, James P. DeLany, Shiguang Liu, Lidiya S. Orlichenko, Georgios Ioannis Papachristou and Dhiraj Yadav, medicine; Catherine J. Baty and Jenny M. Karlsson, cell biology and physiology; Sruti S. Shiva, pharmacology and chemical biology; Kenneth Lee, surgery, and Kyongtae T. Bae and Alessandro Furlan, radiology.

Funding was provided by the National Institutes of Health National Center for Research Resources, the NIH Roadmap for Medical Research and Pitt’s Department of Medicine.

Immunity patterns found in healthy elders

Exceptional cognitive and physical function in old age leaves a telltale immunologic fingerprint, say researchers from Pitt and Children’s Hospital in findings published recently in PLOS: One. They found older adults who have mild impairments also bear a distinct immunologic pattern.

Old age is not synonymous with impairment and disability, noted lead investigator Abbe N. de Vallejo, a faculty member in the medical school’s departments of pediatrics and immunology. “Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed,” he said. “The immune system is dynamic, and the changes it undergoes over time very much influence function.”

For the project, the team collected blood samples from 140 participants ages 78-94 who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants’ health and function, medical history and hospitalizations, and self-rated health and assessed their cognitive and physical function using standard tests.

Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells, de Vallejo said. A closer look in the new study showed that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independent of the conventional ones. The functionally resilient elders also had a distinct profile of blood proteins called cytokines that reflected an immune-enhancing environment.

Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and had a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness.

“These findings indicate that there is remodeling or adaptation of the immune system as we age that can be either protective or detrimental,” de Vallejo said. “Now we have an immunological fingerprint that can identify individuals who are more likely to stay physically and cognitively well.”

He and his colleagues now are studying factors such as genetics and traits developed during childhood that might influence the adaptation of the immune system with advancing age.

Pitt co-authors were Robert M. Boudreau, Graduate School of Public Health’s Department of Epidemiology; David L. Hamel Jr., pediatrics and geriatric medicine; Diane G. Ives, epidemiology; Joshua J. Michel and Robert G. Mueller, pediatrics, and epidemiology chair Anne B. Newman, director of the Center for Aging and Population Health.

The study was funded by the National Institutes of Health.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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