IMMUNE CELLS IN LIVER DRIVE FATTY LIVER DISEASE LIVER CANCER

Fatty liver disease -- alongside fatty liver due to massive alcohol consumption -- is mainly caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary life style. This is referred to as non-alcoholic fatty liver disease (NAFLD). If NAFLD becomes chronic -- e.g. through the constant uptake of high lipids and high sugar combined with lack of excercise a chronic inflammatory response is triggered in the liver tissue in addition. This can lead to non-alcoholic steatohepatitis (NASH) -- a liver disease with clear detectable pathologic alteratons of the tissue.

These liver diseases (NAFLD and NASH), along with chronic viral infections, are the most common causes of liver cancer, or hepatocellular carcinoma (HCC). In the United States, about 90 million people suffer from NAFLD. In Europe, the figure is more than 40 million, and even in threshold countries like India and China, the number of people affected is rising due to increasingly unhealthy lifestyles. More worrying, in all of the above mentioned states the numbers of NAFLD and NASH patients is constantly increasing. Consequently, the incidence of HCC resulting from NASH and NAFLD is also rising worldwide. In the United States, HCC is the fastest-growing form of cancer at the moment. No efficient causal therapy exists for HCC patients of which approximately 800,000 die every year.

T cells involved in the development of fatty liver disease, NASH and HCC

The mechanisms that cause diseases such as fatty liver disease, steatohepatitis and HCC are still not widely understood. However, immune cells, particularly CD8+ T cells and NK T cells seem to play an important role. This finding was made by a team of scientists led by Prof. Mathias Heikenwälder, Prof. Matthias Tschöp, Dr. Kerstin Stemmer, Dr. Kristian Unger, Prof. Ulrike Protzer and the working group of Dr. Hans Zischka from the Helmholtz Zentrum München together with a team headed by Prof. Percy Knolle of the Technische Universität München (TUM), Prof. Achim Weber from Zurich University Hospital and Dr. Monika Wolf, Institute of Surgical Pathology, University Hospital Zurich. The animal model which was used to examine the long-term effects of metabolic syndrome* enabled the scientists to elucidate new mechanisms that cause fatty liver disease and also show how it can develop into liver cancer.

Inflammatory events offer starting point for prevention and treatment

The scientists assume that an existing metabolic imbalance results in the activation and migration of immune cells to the liver. There, the immune cells interact with liver cells and trigger an inflammatory response that damages the liver tissue and also destabilizes the metabolic activity of the liver cells. "Initially it immune cells promote fatty liver degeneration. The inflammation, which is triggered by specific immune cells, encourages the progression of fatty liver pathology and causes NASH to develop. These processes are the basis for liver cell degeneration, which can cause HCC," explains Prof. Heikenwälder, who led the study. "Our results provide completely new insights into the development of these serious liver diseases. Building on this knowledge, we now want to develop new, preventive and therapeutic strategies to combat these diseases." The initial studies are already under way in the preclinical model.

*Metabolic syndrome: a combination of obesity / abdominal adiposity, insulin resistance, raise levels of lipids in the blood and raised blood pressure.

Omega 3 Fatty Acids Promising For Nerve Damage

Today's post from sciencedaily.com (see link below) reinforces the information provided in a post from 2 days ago on this blog and that is that fish oil, reinforced with Omega 3 fatty acids may well be of great benefit to damaged nerves. It has been found that one type of omega 3 fatty acid called resolvins, can restore nerve health in mice. Now we're pretty familiar with studies carried out on long-suffering rodents and can become blasé about yet more potential benefits that haven't been proved in humans. They generally mean that whatever the latest finding may be, it will be years before it reaches our doctor's prescription pad but in this case, taking fish oil supplements to compensate our lack of fish in our diets may not be such a bad idea anyway - if they can also improve our nerve problems in the meantime, until the science proves it beyond doubt, then it's pretty much a win-win situation.

Fish oil may help with diabetic neuropathy
Source:American Physiological Society Date:May 6, 2015 

(APS)Summary:

Approximately 50 percent of patients with diabetes suffer from nerve damage, or neuropathy. No cure exists, and the most effective treatment, keeping blood sugar in control, only slows neuropathy. A new study, however, introduces a new alternative, omega-3 fatty acids found in fish oil. The study shows that fish oil supplements can restore the condition of nerves damaged from diabetes in mice.

"Diabetic neuropathy is a very costly and debilitating complication of diabetes. It is the leading cause of foot ulcers and non-trauma-related amputations, and the impact of diabetic neuropathy on the patient and family are unmeasurable," said Mark Yorek of the VA Medical Center in Iowa City, the study's lead investigator. Fish oil is an attractive treatment approach because "supplements are considered very safe and could be easily translated into everyday care. Fish oil would be easy to take, like a vitamin, and should have few side effects when combined with other medications," explained Yorek.

Previous studies of obesity and diabetes have reported better blood sugar handling, liver function and reduced inflammation with omega-3 fatty acids treatment. The health benefits were attributed to protective molecules produced from omega-3 fatty acids, including one type called resolvins. The research group had previously observed that diets enriched with omega-3 fatty acids from fish oil improved diabetic neuropathy in rats with Type 1 and Type 2 diabetes, and in this new study they examined why.

Researchers used a mouse model of diabetes to study the effect of fish oil. Diabetic mice were fed a high-fat diet and treated with daily injections of resolvin or given a high-fat diet in which half the fat came from fish oil. The results were compared to healthy, non-diabetic mice.

The researchers found that untreated diabetic mice had diminished sense of touch in their paws that corresponded to fewer nerves in the paw's skin and slower transmission of signals along the nerves. The eyes of untreated diabetic mice also had fewer nerves. Though dietary fish oil and resolvin did not lower glucose levels closer to healthy range, they improved nerve health in terms of density and sensory signal transmission. The researchers also observed that resolvin stimulated nerve cells to grow.

"Even though a lot more work needs to be done, including clinical trials with human subjects, our animal studies suggest that fish oil can reverse some of the harmful effects of diabetes on the nerves. Our intent is to do more animal studies to demonstrate that fish oil treatment can reverse the harmful effects of diabetes on nerves even after a long period of poorly controlled diabetes. After completion of this work, we hope to begin studies with diabetic patients with neuropathy," Yorek said.

Story Source:

The above story is based on materials provided by American Physiological Society (APS). Note: Materials may be edited for content and length.

Journal Reference:
Hanna Shevalye, Matthew S Yorek, Lawrence J Coppey, Amey Holmes, Matthew M Harper, Randy H Kardon, Mark A. Yorek. Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes. Journal of Neurophysiology, 2015; jn.00224.2015 DOI: 10.1152/jn.00224.2015

http://www.sciencedaily.com/releases/2015/05/150506182713.htm