U of SC: How non-alcoholic fatty liver disease causes Alzheimer's-like neuroinflammation

July 06, 2020

COLUMBIA, SC -- Research from University of South Carolina associate professor Saurabh Chatterjee's laboratory in Environmental Health Sciences, Arnold School of Public Health, and led by Ayan Mondal, a postdoctoral researcher from the same lab, has revealed the cause behind the previously established link between non-alcoholic fatty liver disease (i.e., NAFLD, recently reclassified as metabolic associated fatty liver disease or MAFLD) and neurological problems. The link they discovered, the unique role of an adipokine (Lipocalin-2) in causing neuroinflammation, may explain the prevalence of neurological Alzheimer's disease-like and Parkinson's disease-like phenotypes among individuals with MAFLD.

The investigators, which include members of Chatterjee's Environment Health & Disease Laboratory and researchers from across UofSC*, published their results in the Journal of Neuroinflammation, a pioneering journal in the field. These findings build on years of research conducted by the interdisciplinary team, which has unearthed previously unknown pathways and mechanisms between the liver and the gut microbiome with other parts of the body through their focus on how environmental toxins contribute to liver disease, metabolic syndrome and obesity.

MAFLD affects up to 25 percent of Americans and much of the global population - many of whom are unaware of their condition. Yet the effects of this silent disease are far-reaching, possibly leading to cirrhosis, liver cancer/failure and other liver diseases. The findings from the current study not only confirm the strong correlation between MAFLD and neuroinflammation/neurodegeneration that has been established by other recent research, but it explains how this happens.

"Lipocalin 2 is one of the important mediators exclusively produced in the liver and circulated throughout the body among those who have nonalcoholic steatohepatitis - or NASH - which is a more advanced form of MAFLD," Chatterjee says. "The research is immensely significant because MAFLD patients have been shown to develop Alzheimer's and Parkinson's-like symptoms as older adults. Scientists can use these results to advance our knowledge in neuroinflammatory complications in MAFLD and develop appropriate treatments."

Ninety percent of the obese population and 40 - 70 percent of those with type 2 diabetes appear to have MAFLD, according to the Centers for Disease Control and Prevention. In addition to overweight/obese status and diabetes, other risk factors include high cholesterol and/or triglycerides, high blood pressure and metabolic syndrome.

These individuals have a higher risk for having diseased livers, which are associated with increased lipocalin 2 - as found in the present study. The lipocalin 2 circulates throughout the body at higher levels, possibly inducing inflammation in the brain.

"Chronic neuroinflammation is a critical element in the onset and progression of neurodegenerative diseases, including Alzheimer's disease," says Prakash Nagarkatti, UofSC Vice President for Research and a member of the research team.

"Our study may help design new therapeutic approaches to counter the neuroinflammatory pathology in NASH but also in other related brain pathology associated with chronic inflammatory diseases," adds Chatterjee.
-end-
*Co-authors include Ayan Mondal, Dipro Bose, Punnag Saha, Sutapa Sarkar, Ratanesh Seth, Diana Kimono, Muayad Albadrani, Mitzi Nagarkatti, Prakash Nagaratti.

This work has been supported by National Institutes of Health Awards 2-P20-GM-103641-06 (Project 4), 1-P01-ES-028942-01(Tox Core), and P01-AT-003961 (Project 4) to S. Chatterjee; and P01-AT-003961, P20-551 GM-103641, to M. Nagarkatti and P. Nagarkatti.

About University of South Carolina

The University of South Carolina is a globally recognized, high-impact research university committed to a superior student experience and dedicated to innovation in learning, research and community engagement. Founded in 1801, the university offers more than 350 degree programs and is the state's only top-tier Carnegie Foundation research institution. More than 50,000 students are enrolled at one of 20 locations throughout the state, including the research campus in Columbia. With 56 nationally ranked academic programs including top-ranked programs in international business, the nation's best honors college and distinguished programs in engineering, law, medicine, public health and the arts, the university is helping to build healthier, more educated communities in South Carolina and around the world.

University of South Carolina

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.