Aerobic exercise could have the final say on fatty livers
July 29, 2020
Science Daily/Trinity College Dublin
A new study from Trinity College Dublin highlights that fitness may be a more important clinical endpoint for improvement in patients with fatty liver diseases during exercise trials, rather than weight loss. The findings have been published today (Tuesday, 28th July 2020) in the medical journal Alimentary Pharmacology and Therapeutics.
Metabolic associated fatty liver disease (MAFLD) is a condition characterised by a build up of fat in the liver. The liver is central to a suite of vital processes in the body including digestion, blood clotting and energy production.
If left untreated, MAFLD can lead to serious complications like liver fibrosis (scarring), cirrhosis, liver failure and liver cancer, as well as cardiovascular and metabolic issues. Risk factors for developing MAFLD include type 2 diabetes and obesity. The global estimated prevalence of MAFLD is 25%, making it the leading cause of chronic liver disease worldwide, and is quickly becoming the leading cause of cirrhosis and liver cancer in liver transplant candidates in the western world.
Up to now, due to the lack of approved pharmacological interventions, treatment has been a combination of prescribed weight loss and physical activity, with a weight loss target of 7-10% being the primary treatment endpoint. There is some evidence that exercise training alone without significant weight loss can reduce liver fat content (assessed using non-invasive methodologies such as transient elastography and ultrasound) in MAFLD patients. However, the independent effects of exercise alone on biopsy-measured outcomes (the gold standard for diagnosing and assessing MAFLD) have been unknown.
This new study highlights that increased fitness, the result of aerobic exercise participation, may be a more important clinical endpoint for improvement in MAFLD patients during exercise trials, rather than weight loss.
In Ireland and worldwide, MAFLD is a silent epidemic. In Ireland, there is currently no national screening programme for the disease, so the true prevalence in Ireland is unknown. However, St James's Hospital, Dublin, where the study took place, now has over 1000 patients on their own database, with the numbers growing year on year.
The Trinity study is the first to demonstrate significant improvements in biopsy-measured liver outcomes in a MAFLD cohort following an exercise-only intervention, without clinically significant weight loss. The study also demonstrates that improvements in biopsy-measured liver outcomes were significantly related to improvements in fitness levels. The study also found however, that when patients were followed up longitudinally, none of the benefits of the exercise intervention were sustained.
The study is unique in that it used repeat biopsies in MAFLD patients during an exercise-only intervention. Only two previous studies have been conducted using repeat biopsies in exercise-only trials, but these studies had significant methodological limitations. These studies used low-intensity resistance exercise and lacked exercise supervision, which may have led to non-significant changes on liver biopsy outcomes. This study is also the first to relate improvements on liver biopsies with improvements in fitness, suggesting a potential interrelationship between the two outcomes.
Dr Philip O'Gorman, Department of Physiotherapy, Trinity College said:
"The benefits of exercise training on both liver and cardiometabolic outcomes for these patients is very clear. Our findings suggest that there is an urgent need to better transition exercise into the community setting for these patients as the benefits of exercise intervention were not sustained longitudinally. This study clearly demonstrates the clinical benefit of exercise in MAFLD in as little as 12 weeks and shows the clinical benefit of improving cardiorespiratory fitness, which is increasingly being considered a 'clinical vital sign.'
Worryingly, there is little to no exercise referral systems in place within hospital departments and beyond throughout the healthcare system in Ireland. However, as our results have shown, the lack of sustainability of the benefits of exercise in MAFLD is concerning and there is an urgent unmet need to enable patients to continually engage in exercise therapy in the community setting. A systems-based approach whereby clinicians can refer patients to exercise specialists in the community is required for long-term benefits of exercise to be sustained."
https://www.sciencedaily.com/releases/2020/07/200729114728.htm
The gut shields the liver from fructose-induced damage
June 29, 2020
Science Daily/University of Pennsylvania School of Medicine
After one consumes food or a beverage containing fructose, the gastrointestinal system, or gut, helps to shield the liver from damage by breaking down the sugar before it reaches the liver, according to a new multi-center study led by researchers in the Perelman School of Medicine at the University of Pennsylvania. However, the consumption of too much fructose -- particularly in a short period of time -- can overwhelm the gut, causing fructose to "spill over" into the liver, where it wreaks havoc and causes fatty liver, researchers discovered.
The findings, in mice, help to unravel longstanding questions about how the body metabolizes fructose -- a form of sugar often found in fruits, vegetables, and honey, as well as most processed foods in the form of high fructose corn syrup. Consumption of fructose has increased 100-fold over the last century, even as studies have shown that excessive consumption, particularly sweet drinks, are linked to non-alcoholic fatty liver disease, obesity and diabetes. The findings were published in Nature Metabolism.
"What we discovered and show here is that, after you eat or drink fructose, the gut actually consumes the fructose first -- helping to protect the liver from fructose-induced damage," said the study's corresponding author Zoltan Arany, MD, PhD, a professor of Cardiovascular Medicine at Penn. "Importantly, we also show that consuming the food or beverage slowly over a long meal, rather than in one gulp, can mitigate the adverse consequences."
Studies have shown that the excessive consumption of fructose can be toxic to the liver. When large quantities of fructose reach the liver, the liver uses excess fructose to create fat, a process called lipogenesis. Eventually, people who consume too much fructose can develop nonalcoholic fatty liver disease, a condition in which too much fat is stored in the liver cells.
Until now, it hasn't been clear whether the gut's role in processing the fructose prevents or contributes to fructose-induced lipogenesis and the development of liver diseases. For this study, the team of researchers, including Princeton University's Joshua Rabinowitz, MD, PhD, studied a key enzyme, called ketohexokinase, that controls how fast fructose is consumed. They showed, by genetically engineering mice, that lowering the levels of this enzyme in the gut led to fatty livers in the mice. Conversely, the team showed that increasing the level of ketohexokinase in the gut protected from fatty liver. Thus, the researchers found the breakdown of fructose in the gut mitigates the development of extra fat in liver cells in mice. They discovered that the rate at which the intestine can clear fructose determines the rate at which fructose can be safely ingested.
In addition, the team showed the same amount of fructose is more likely to result in the development of fatty liver when its consumed via a beverage versus food. Similarly, one faces an increased likelihood of developing fatty liver when consuming fructose in a single setting compared to several doses spread over 45 minutes.
"Collectively, our findings show fructose induces lipogenesis when the intake rate exceeds the gut's capacity to process fructose and protect the liver," Arany said. "In the modern context of excessive availability and consumption of processed foods, it is easy to see how the resulting fructose spillover would drive metabolic syndrome."
Researchers noted that more work is needed to determine the extent to which these findings in mice extend to humans. Additional Penn authors include Shogo Wada, Steven Yang and Bridget Gosis.
https://www.sciencedaily.com/releases/2020/06/200629120250.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
Defining obesity in children should be based on health issues, not just BMI
Mental health issues are consistent across BMI groups
April 2, 2019
Science Daily/McMaster University
A new study aims to identify what influences the success participants achieve in weight management programs and help improve these programs. The study follows participants for three years.
Physicians are told to gauge the severity of a child's problem with obesity using the body mass index (BMI) that measures weight against height. But that doesn't work well to identify health issues, especially those of mental health, in children with obesity seeking care, says a study led by McMaster University.
Other medical issues, including high blood pressure, prediabetes and non-alcoholic fatty liver disease are also common, and are only slightly more frequent in those with the most severe obesity compared to those with less severe obesity, according to the study.
The details of the study called the Canadian Pediatric Weight Management Registry (CANPWR) were published today in The Lancet Child & Adolescent Health. This study found two thirds of children entering weight management programs across Canada have severe obesity based on their BMI.
"We found that social and mechanical health issues were more common in those with the highest body mass index. However, mental health issues, for example, are consistent across the BMI groups," said Katherine Morrison, principal investigator of the CANPWR study, and professor of the Department of Pediatrics at McMaster.
"If you are only using BMI to identify the youth who need the most care, you would be presuming the kids with the lowest BMI class would be the least likely to have mental health issues or metabolic issues, but our findings suggest this is not true. This study suggests that using a clinical staging system, one that evaluates the health of the child and not just the BMI, is likely the best approach."
Morrison is also co-director of the Centre for Metabolism, Obesity and Diabetes Research at McMaster, an investigator of the Population Health Research Institute, and a pediatric endocrinologist at McMaster Children's Hospital. She said the end goal is to improve care of these children.
"There is a lot said about preventing obesity, we also really need to focus on how best to treat children with obesity. This is especially true when we see the burden of health illness that is associated with obesity in children entering weight management programs."
The CANPWR study aims to identify what influences the success participants achieve in weight management programs and help improve these programs. The study follows participants for three years.
The 10 clinics taking part in the study are in Vancouver, Edmonton, Calgary, Toronto, Hamilton, Ottawa and Montreal.
The paper used information from 847 children with obesity and the health issues were determined at their initial visit to one of the multidisciplinary weight management clinics across Canada. Participants were aged five to 17 at the time of enrolment.
In this study, researchers showed that using a clinical staging system called the Edmonton Obesity Staging System for Pediatrics, or EOSS-P, was more useful for understanding the health issues of the children in these clinics than the BMI class system. They suggest that using a clinical staging system will better assist the design of health care interventions for children with obesity.
Obesity-related health issues were common. Mental health concerns were the most common (90 per cent), followed by metabolic (85 per cent), social (65 per cent) and mechanical (62 per cent) health issues. The most common mental health issue identified was anxiety.
The most commonly identified metabolic health complication was dyslipidemia, followed by non-alcoholic fatty liver disease.
Bullying was the most commonly identified social health factor, followed very closely by low household income. More than one-third of children in the highest obesity group came from low income homes, which was significantly higher than those with lower levels of obesity.
Those with the most severe obesity by BMI were more likely to have experienced bullying, and more likely to report difficulties with peer relationships, compared to the less severe obesity groups.
https://www.sciencedaily.com/releases/2019/04/190402215621.htm