THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Advances in metabolic research offer new insight into rheumatic diseases

Recent research findings provide new information about how adiposity leads to a systemic inflammatory state and to metabolic derangement, the relationship between osteoarthritis (OA), metabolic signaling and adipokines, and metabolic profiling in rheumatoid arthritis (RA) patients.

Experts will discuss the current understanding of metabolic syndrome and inflammation and offer examples of how metabolically driven inflammation relates to disease mechanisms and clinical phenotypes in arthritis during Adiposity & Arthritis from 2:30 – 4:00 pm Monday in Room 24 A.

Edgar Engleman, MD
Edgar Engleman, MD

Edgar Engleman, MD, will discuss the relationship between adiposity, inflammation, and metabolic derangement.

“We’ve found that mice placed on a high-fat diet develop inflammation in the fatty tissues, particularly in the deep fatty tissues, that is quite profound,” said Dr. Engleman, Professor of Pathology and Medicine, Medical Director of the Stanford Blood Center, and Co-Director of the Tumor Immunology and Immunotherapy Program of the Stanford Cancer Institute at Stanford University in Palo Alto, CA. “It involves multiple immune cell types, including macrophages and T cells, and this inflammation is a cause of insulin resistance, the precursor of type 2 diabetes.”

Dr. Engleman also said studies in human obese individuals have found inflammatory changes in the adipose tissues of those individuals, as well, that are associated with insulin resistance.

“While we have not yet done work relating this chronic inflammatory state to other diseases, I believe that subclinical inflammatory changes potentially underlie a great many diseases,” Dr. Engleman said. “We know that inflammation underlies rheumatologic disorders, virtually all of them, but it could also be important in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and non-alcoholic fatty liver disease, and there’s no question that it’s important in atherosclerotic heart disease.”

Timothy Griffin, PhD
Timothy Griffin, PhD

Timothy Griffin, PhD, an Associate Member in the Aging and Metabolism Research Program at the Oklahoma Medical Research Foundation and an Adjunct Associate Professor at the University of Oklahoma Health Sciences Center in Oklahoma City, will talk about the roles of adipokines, metabolic/nutrient factors, and signaling pathways in the pathogenesis of OA.

“We know that obesity is a major risk factor for osteoarthritis and there are some compelling new findings emerging on how some metabolic factors, such as inflammation associated with adipose tissue, are altered in osteoarthritic conditions and may be involved in the progression of osteoarthritis,” Dr. Griffin said.

In their research, Dr. Griffin and his colleagues are currently attempting to dissect the metabolic factors that are potentially involved. Using preclinical animal models, they’re looking at different types of diet and the role of elevated sucrose versus elevated fat in the diet, specifically looking at how they affect changes in chondrocyte metabolism.

“We’re at an exciting time in the field, as we’re starting to understand the biology of the tissues involved in osteoarthritis and the factors related to altered metabolism and obesity that directly impact many of these tissues,” Dr. Griffin said. “We know that osteoarthritis is not just a wear-and-tear disease anymore, but it’s really an activated process.”

Stephen Young, PhD
Stephen Young, PhD

The final presenter of the symposium, Stephen Young, PhD, Member of the Rheumatology Research Group at the Institute of Inflammation and Ageing at the University of Birmingham in the U.K., will discuss metabolic profiling in rheumatoid arthritis.

“Because metabolism is influenced by both our genes and our environment, it suggests that metabolism and metabolic changes may reflect not only an individual’s set of genes, but also the disease processes going on in that individual,” Dr. Young said. “Therefore, metabolomics can be a good way of looking at a summative assessment of an individual patient.”

Dr. Young will describe ongoing research in which he and his colleagues have sampled biofluids from a number of different diseases, including rheumatoid arthritis. He said that by using NMR spectroscopy they have been able to develop metabolic profiles based on the small chemicals and metabolites found in the blood and urine.

“We’ve taken serum from RA patients, mainly in early disease when they’ve only had their joint symptoms for a matter of weeks or a few months, and have been able to make a prediction about whether they’re going to develop chronic RA or have a self-limiting disease,” Dr. Young said. “We’ve identified a number of metabolic pathways that may be useful in suggesting novel therapeutic targets that would allow us to provide personalized medicine and much better outcomes for our patients.”