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
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
Obesity crisis blamed for a rise in fatty liver disease amongst young adults
January 15, 2020
Science Daily/University of Bristol
One in five young people have fatty liver disease (steatosis), with one in 40 having already developed liver scarring (fibrosis), research published today [15 January] has found. The study, published in The Lancet Gastroenterology & Hepatology, is the first to attempt to determine the prevalence of fatty liver disease and fibrosis in young healthy adults in the UK.
Fatty liver disease is a condition in which fats build up in the cells of the liver. It is broadly split into non-alcoholic fatty liver disease (NAFLD), which is usually seen in people who are overweight or obese, and alcohol related fatty liver disease, which is associated with harmful levels of drinking. If left untreated both can lead to fibrosis (scarring of the liver) and in severe cases eventually cirrhosis of the liver, which is irreversible. Worldwide NAFLD affects approximately a quarter of adults in developed countries.
The research, conducted by Dr Kushala Abeysekera and researchers from the University of Bristol, looked at data collected from 4,021 participants of the Children of the 90s study also known as Avon Longitudinal Study of Parents and Children (ALSPAC). Based in Bristol, participants from the health study -- who had previously been assessed for NAFLD as teenagers using ultrasound -- were invited for assessment using transient elastography with FibroScan as part of the Focus @24 clinic.
Researchers first looked at those participants who did not report harmful alcohol consumption and found that one in five had non-alcoholic fatty liver disease. On widening the data to include all participants, they again found that over 20 per cent displayed evidence of fatty liver and one in 40 had already developed fibrosis, with those participants who had both fatty liver and harmful alcohol use at greatest risk of liver scarring. As a comparison, at 17 years of age, 2.5 per cent of participants had moderate to severe levels of fatty liver, whilst at the age of 24 this number had increased to 13 per cent.
Dr Abeysekera, Honorary Lecturer in the Bristol Medical School: Population Health Sciences, explained: "Children of the 90s data has highlighted the potential importance of liver health amongst young adults. This age group remains a blind spot for clinicians, as they are typically considered a "healthy" age group that are rarely studied. If the obesity epidemic and culture of alcohol abuse aren't tackled nationally, we may see increasing numbers of patients presenting with end-stage liver disease, and at earlier ages.
"It is important to note that whilst we identified that 20 per cent of the cohort had fatty liver -- only a small percentage of the individuals will go on to develop cirrhosis (irreversible liver scarring), and the vast majority of participants should be fine if they manage their diet and exercise appropriately."
The next steps will be to take a closer look at how environmental and genetic factors may lead to individuals developing non-alcoholic fatty liver disease earlier in life.
https://www.sciencedaily.com/releases/2020/01/200115191527.htm