Inflammation can lead to circadian sleep disorders

October 31, 2018

CHICAGO --- Inflammation, which is the root cause of autoimmune disorders including arthritis, Type 1 diabetes, irritable bowel syndrome and Crohn's disease, has unexpected effects on body clock function and can lead to sleep and shiftwork-type disorders, a new Northwestern Medicine study in mice found.

The study was published in the journal Genes & Development.

The study used a new technology -- a genetic switch -- to turn inflammation on and off in genetically modified mouse models. When researchers deactivated inflammation, the mouse was unable to tell what time it was and was unable to keep an intact rest-activity cycle.

In addition to this new technology, the study was novel because, for the first time, scientists saw a link between what causes inflammation and what controls the body's clock.

In inflammatory diseases, the body experiences an excess of a genetic factor known as NF-kappa beta (NFKB), the study found. NFKB is a catalyst for a set of chain reactions, or pathway, that leads to the pain and tissue destruction patients feel in inflammatory diseases. That same chain-reaction catalyst also controls the body's clock.

"NFKB alters the core processor through which we tell time, and now we know that it is also critical in linking inflammation to rest-activity patterns," said senior author Dr. Joseph Bass, the Charles F. Kettering Professor of Medicine and director of the Center for Diabetes and Metabolism at Northwestern University Feinberg School of Medicine.

When people have sore muscles and take an ibuprofen to reduce the inflammation, they are essentially trying to turn down the activation of inflammation, which is similar to what the authors did in this study, Bass said.

The findings also have implications for diet and provide a detailed roadmap to understanding the fundamental mechanisms by which inflammation -- including the inflammation that occurs when someone chronically consumes a high-fat diet -- and likely other instigators lead to circadian disorders.

The scientists sought to understand how a high-fat diet might affect the perception of time at the tissue level, which is what led to their study of inflammation, said first author Hee-Kyung Hong, research assistant professor of endocrinology at Feinberg.

One of the reasons Western diet contributes to diabetes, cardiovascular disease and even certain cancers is thought to be the inappropriate trigger of inflammation, so a unifying idea is that impaired time-keeping may be one of the links between diet and disease.

"We don't know the reasons, but this interaction between the inflammation and clocks is not only relevant to understanding how inflammation affects the brain and sleep-wake cycle but also how immune or fat cells work," Hong said.
-end-
The study is titled, "Requirement for NF-κB in Maintenance of Molecular and Behavioral Circadian Rhythms in Mice." Other Northwestern co-authors include Eleonore Maury, Kathryn Moynihan Ramsey, Mark Perelis, Biliana Marcheva, Chiaki Omura, Yumiko Kobayashi and Grant D. Barish.

This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK090625 and R01DK100814, National Institute on Aging (NIA) grant P01AG011412, and Chicago Biomedical Consortium S-007 to J.B.; NIDDK grant R01DK108987, National Institute of Child Health and Human Development (NICHD) grant R01 HD089552, and American Diabetes Association (ADA) grant 1-17-IBS-137 to G.D.B.; and the Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques (ALFEDIAM) grant to E.M.

Northwestern University

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.