New research explores the urea cycle's strong connection to fatty liver disease

Medical Xpress / Indiana University School of Medicine / Cell Metabolism ^ | Aug 13, 2024 | Yiming Zhang et al

[ConservativeMind]

A physician scientist is making strides in understanding the molecular origins of fatty liver disease, a leading cause of liver failure. By identifying the critical role the urea cycle plays in its development, his findings could pave the way for new medications to treat this currently incurable disease.

In a study, Brian DeBosch, MD, Ph.D., uncovered a critical link between defects in the urea cycle, a key process in detoxifying ammonia in the body, and the development of fatty liver disease.

The study found that these urea cycle defects lead to secondary impairment in the tricarboxylic acid (TCA) cycle, a key pathway for energy metabolism. This disruption results in inefficient calorie utilization and excessive fat storage in the liver, which can subsequently cause inflammation and fibrosis, contributing to the progression of the disease.

DeBosch collaborated with Yin Cao, ScD, MPH. Cao analyzed blood metabolites from a cohort of 106,600 healthy patients from the United Kingdom Biobank. Her examination revealed that certain metabolites associated with nitrogen and energy metabolism, as well as mitochondrial function, can predict the risk of severe liver diseases even in healthy individuals.

In a 2022 study, DeBosch and his team found that administering an enzyme called pegylated arginine deiminase (ADI-PEG 20) significantly improved symptoms of fatty liver and obesity in mice, offering promising insights for future therapies. Their latest findings further suggest that targeting nitrogen handling in the liver, a process linked to the urea cycle, could be an effective treatment approach.

Additionally, their research demonstrated that giving mice a precursor to adenine dinucleotide (NAD+), an important intermediary that fosters TCA cycle function, also improved function in their study models. Looking ahead, DeBosch plans to continue exploring the effects of ADI-PEG 20 and NAD+ to investigate their molecular connections between the urea and TCA cycles.

[ConservativeMind]

It appears from the paper they found liver function improved with either nicotinamide riboside or nicotinamide mononucleotide, both of which are available as supplements and help with making NAD+.

[ConservativeMind]

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[rexthecat]

Fatty liver disease is often associated with high consumption of sugary soda drinks, as well as alcohol of course.

[Rockingham]

A friend of mine died from fatty liver disease, which was not diagnosed until late in life. He was a determined teetotaler but devoted to Coke and pastries.

[nagant]

Alcohol and fructose are both metabolized through the same ALDH2 pathway.

[Rockingham]

Sadly, in spite of being married to a highly capable doctor, my friend's Non-Alcoholic Fatty Liver Disease was diagnosed too late to make a difference and he suffered from obesity and heart disease. By the end, he seemed in many ways a defeated man weighed down by his medical death sentence.

Yet my friend was still game and retained his characteristic charm, intelligence, love for and loyalty to family and friends, and eagerness to participate in life. His talent was such that, with good health, he would have become a successful and nationally known conservative lawyer, public official, author, or talk show host.

[Bigg Red]

Are there foods that provide those compounds?

[DollyCali]

Good question. Nicotine-ish?