Exercise promotes healthy living and a healthy liver
April 12, 2021
Science Daily/University of Tsukuba
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide, affecting as much as a quarter of humanity. It is characterized by fat accumulation in liver cells and may progress to inflammation, cirrhosis and liver failure. Now, researchers at the University of Tsukuba reveal the positive effects, beyond the expected weight-loss benefit, of exercise on the liver.
NAFLD is associated with unhealthy behaviors such as overeating and a sedentary lifestyle. In Japan 41% of middle-aged men have NAFLD and 25% will progress to non-alcoholic steatohepatitis (NASH) and hepatic dysfunction.
Weight reduction is fundamental to NAFLD management. Unfortunately, achieving a targeted bodyweight without supervision is difficult, and maintaining this over time even more so. Hitherto, exercise was considered adjunctive to dietary restrictions for weight loss but the other benefits such as reduced hepatic steatosis (fatty change) and stiffness are being increasingly recognized. However, the underlying mechanisms remain unclear.
"We compared data from obese Japanese men with NAFLD on a 3-month exercise regimen with those on dietary restriction targeting weight loss," senior author Professor Junichi Shoda explains. "We tracked hepatic parameters, reduction in adipose tissue, increase in muscle strength, reductions in inflammation and oxidative stress, changes in organokine concentrations, and expression of target genes of Nrf2, an oxidative stress sensor."
The researchers found that exercise preserved muscle mass better, though with modest decrease of body and fat mass. Remarkably, ultrasound elastography revealed that the exercise regimen reduced liver steatosis by an additional 9.5%, liver stiffness by an additional 6.8%, and the FibroScan-AST Score (a measure of liver fibrosis) by an additional 16.4% over the weight-loss regimen.
Additionally, the exercise regimen altered the circulating concentrations of specific organokines and apparently induced anti-inflammatory and anti-oxidative stress responses through activation of the Nrf2 (nuclear factor E2-related factor 2), an oxidative stress sensor. It also enhanced the phagocytic capacity of Kupffer cells which help maintain liver function.
Professor Shoda explains the relevance of their findings. "Our research shows how exercise prevents liver steatosis and fibrosis in NAFLD and clarifies that this benefit is compounded by preservation of muscle mass and is independent of weight changes. Patients on exercise regimens may become demotivated and drop out if they do not experience significant weight loss. Therefore, moderate to vigorous intensity exercise should be integrated in all NAFLD therapeutic regimens, and patients at risk for NASH should be encouraged to persevere with moderate to high intensity exercise regardless of whether or not they lose weight."
https://www.sciencedaily.com/releases/2021/04/210412101923.htm
Universal gut microbiome-derived signature predicts cirrhosis
June 30, 2020
Science Daily/University of California - San Diego
Researchers report that stool microbiomes of NAFLD patients are distinct enough to potentially be used to accurately predict which persons with NAFLD are at greatest risk for having cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, affecting an estimated one-quarter of the global population. It is a progressive condition that, in worst cases, can lead to cirrhosis, liver cancer, liver failure and death.
In a new paper published online June 30, 2020 in Cell Metabolism, a team of scientists, led by researchers at University of California San Diego School of Medicine, report that stool microbiomes -- the collection of microorganisms found in fecal matter and in the gastrointestinal tract -- of NAFLD patients are distinct enough to potentially be used to accurately predict which persons with NAFLD are at greatest risk for having cirrhosis -- the late-stage, irreversible scarring of the liver that often requires eventual organ transplantation.
"The findings represent the possibility of creating an accurate, stool microbiome-based, non-invasive test to identify patients at greatest risk for cirrhosis," said senior author Rohit Loomba, MD, professor of medicine in the Division of Gastroenterology at UC San Diego School of Medicine and director of its NAFLD Research Center. "Such a diagnostic tool is urgently needed."
Loomba said a novel aspect of the study is the external validation of gut microbiome signatures of cirrhosis in participant cohorts from China and Italy. "This is one of the first studies to show such a robust external validation of a gut microbiome-based signature across ethnicities and geographically distinct cohorts.
The work builds upon previous published research in 2017 and 2019 by Loomba and colleagues.
A link between NAFLD and the gut microbiome is well-documented, but specifics were scant and it has not been clear that discrete metagenomics and metabolomics signatures might be used to detect and predict cirrhosis. In the latest study, researchers compared the stool microbiomes of 163 participants encompassing patients with NAFLD-cirrhosis, their first-degree relatives and control-patients without NAFLD.
Combining metagenomics signatures with participants' ages and serum albumin (an abundant blood protein produced in the liver) levels, the scientists were able to accurately distinguish cirrhosis in participants differing by cause of disease and geography.
The next step, said Loomba, is to establish causality of these gut microbial species or their metabolites in causing cirrhosis, and whether this test can be used and scaled up for clinical use.
https://www.sciencedaily.com/releases/2020/06/200630125126.htm
Natural compound in vegetables helps fight fatty liver disease
New research shows how indole can reduce inflammation, fatty deposits
February 7, 2020
Science Daily/Texas A&M AgriLife Communications
A new study led by Texas A&M AgriLife Research scientists shows how a natural compound found in many well-known and widely consumed vegetables can also be used to fight fatty liver disease.
The study demonstrates how non-alcoholic fatty liver disease, or NAFLD, can be controlled by indole, a natural compound found in gut bacteria -- and in cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts. It also addresses how this natural compound may lead to new treatments or preventive measures for NAFLD.
The study was recently published in Hepatology.
"Based on this research, we believe healthy foods with high capacity for indole production are essential for preventing NAFLD and are beneficial for improving the health of those with it," said Chaodong Wu, M.D., Ph.D., a Texas A&M AgriLife Research Faculty Fellow and principal investigator for the study. "This is another example where altering the diet can help prevent or treat disease and improve the well-being of the individual."
About NAFLD and indole
NAFLD occurs when the liver becomes "marbled" with fat, sometimes due to unhealthy nutrition, such as excessive intake of saturated fats. If not properly addressed, this condition can lead to life-threatening liver disease, including cirrhosis or liver cancer.
Many diverse factors contribute to NAFLD. Fatty liver is seven to 10 times more common in people with obesity than in the general population. In addition, obesity causes inflammation in the body. Driving this inflammation are macrophages, types of white blood cells that normally battle infection. This inflammation exacerbates liver damage in those with liver disease.
Gut bacteria can also have an effect -- either positive or negative -- on the progression of fatty liver disease. These bacteria produce many different compounds, one of which is indole. This product of the amino acid tryptophan has been identified by clinical nutritionists and nutrition scientists as likely having preventive and therapeutic benefits to people with NAFLD.
The National Cancer Institute also notes the benefits of indole-3-carbinol found in cruciferous vegetables, including their anti-inflammatory and cancer-fighting properties.
A comprehensive and multi-level study on fatty liver disease
The present study examined the effect of indole concentrations on people, animal models and individual cells to help determine indole's effect on liver inflammation and its potential benefits to people with NAFLD. It investigated the extent to which indole alleviates non-alcoholic fatty liver disease, incorporating previous findings on gut bacteria, intestinal inflammation and liver inflammation. It also incorporated investigation into how indole improves fatty liver in animal models.
For the study, researchers investigated the effects of indole on individuals with fatty livers. As research collaborator Qifu Li, M.D., was also a physician at Chongqing Medical University in China, the team decided he should lead the clinical research using Chinese participants.
In 137 subjects, the research team discovered people with a higher body mass index tended to have lower levels of indole in their blood. Additionally, the indole levels in those who were clinically obese were significantly lower than those who were considered lean. And in those with lower indole levels, there was also a higher amount of fat deposition in the liver.
This result will likely extend to other ethnicities, Li noted, though ethnic background may have some influence on gut bacteria populations and the exact levels of metabolites.
To further determine the impact of indole, the research team used animal models fed a low-fat diet as a control and high-fat diet to simulate the effects of NAFLD.
"The comparisons of animal models fed a low-fat diet and high-fat diet gave us a better understanding of how indole is relevant to NAFLD," said Gianfranco Alpini, M.D., a study collaborator and former distinguished professor of Texas A&M Health Science Center, now the director of the Indiana Center for Liver Research.
Alpini said treatment of NAFLD-mimicking animal models with indole significantly decreased fat accumulation and inflammation in the liver.
The research team also studied how indole affected individual cells.
Shannon Glaser, M.D., a professor of Texas A&M Health Science Center, said that in addition to reducing the amount of fat in liver cells, indole also acts on cells in the intestine, which send out molecular signals that dampen inflammation.
"The link between the gut and the liver adds another layer of complexity to studies on non-alcoholic fatty liver disease, and future studies are very much needed to fully understand the role of indole," Glaser said.
Additional nutrition research needed
"Foods with a high capacity of indole production or medicines that mimic its effects may be new therapies for treatment of NAFLD," Wu said, adding prevention is another important aspect to consider.
"Preventing NAFLD's development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively," he said. "Future research is needed to investigate how certain diets may be able to achieve this."
Wu said in future research he hopes to collaborate with food scientists and clinical nutritionists to examine what healthy foods can alter gut microbiota and increase indole production.
https://www.sciencedaily.com/releases/2020/02/200207123746.htm