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liver health

Liver, Brain, Inflammation and Cognition

Liver, Brain, Inflammation and Cognition

An October 2024 study of mice by University of Oklahoma College of Medicine said,

  • “We hypothesize that when liver necroptosis is activated, the liver secretes toxic or inflammatory molecules that enter the bloodstream and cross the blood-brain barrier, where they cause inflammation in the brain,”

  • “This type of organ crosstalk is becoming very important in research. Usually, when we study a disease condition, we focus on one organ, but when we do that, we miss the systemic effect.”

  • “This study tells us that, with age-associated cognitive decline or Alzheimer’s disease, we shouldn’t think only about targeting the brain. We also need to think about how liver inflammation plays a role,”

  • “What we have found in our mice studies so far matches what is reported for patients – that people with liver diseases have high inflammation in the liver and also have cognitive issues,”

  • “Our key question is what is causing this increase in inflammation in aging? It is important that we advance our knowledge in this area because it is critical that we develop new ways to treat these diseases.”

Bad Cholesterol consumed by liver immune system

Bad Cholesterol consumed by liver immune system

A March 2024 study by the Karolinska Institutet, Sweden on how immune cells in the liver react to high cholesterol levels and eat up excess cholesterol that can otherwise cause damage to arteries, said,

  • “Essentially, we wanted to detonate a cholesterol bomb and see what happened next,”

  • “We found that the liver responded almost immediately and removed some of the excess cholesterol.”

  • “We were surprised to see that the liver seems to be the first line of defence against excess cholesterol and that the Kupffer cells were the ones doing the job,”

  • “This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.”

  • “Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis,”

  • “This could help us develop more holistic and effective strategies to combat this common and deadly disease.”

New Orgenelle in Liver

New Orgenelle in Liver

A March 2024 study by First Hospital of Jilin University reports on a new organelle called the mitochondria-lysosome-related organelle (MLRO). It is unique in that it formed by the fusion of a mitochondrion and a lysosome, a cellular "garbage disposal" unit. It provides an alternative way to break down damaged cell parts.

Dietary Fat, Liver Health

Dietary Fat, Liver Health

A December 2022 study by Sinshu University Graduate School of Medicine, Japan, said

  • “Dietary Trans-fatty acid (TFA), saturated fatty acid (SFA), and cholesterol are present in a variety of food sources. For instance, cholesterol is abundant in animal-derived foods like eggs, cheese, shellfish, meats, sardines, and full-fat yogurt. Whereas SFA is primarily found in animal and plant products such as red meat, dairy items, palm oil, and coconut oil, TFA naturally occurs in dairy products and animal meat in relatively smaller amounts. Certain products, such as partially hydrogenated vegetable oils, contain relatively larger amounts of TFA.”

  • “Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators like CD31 and TEK receptor tyrosine kinase, in addition to lymphatic vessel endothelial hyaluronan receptor 1. We also detected elevated levels of vascular endothelial growth factor C and fibroblast growth factor receptors 2 and 3, as well as c-Jun N-terminal kinase and hypoxia-inducible factor 1α in the mice livers.” 

  • “We demonstrated for the first time that hepatic angiogenesis and lymphangiogenesis were enhanced by saturated-fat- or trans-fat-rich diets, but not cholesterol-rich diets, mainly through the JNK-HIF1α-VEGF-C axis. These processes are crucial targets for treating hepatocellular carcinoma.”

  • “Agents inhibiting hepatic angiogenesis are widely used for treating hepatocellular carcinoma. However, I also recommend avoiding fatty-acid-rich diets especially if someone is at a high risk of developing liver cancer or undergoing treatment for liver cancer.”

Kisspeptin and Liver Disease

Kisspeptin and Liver Disease

An April 2022 study by Rutgers said,

  • “This work shows the kisspeptin receptor signaling pathway has a potential therapeutic role in Non-Alcoholic Fatty Liver Disease.”

  • “It does this by protecting against the development of fat in the liver and reducing inflammation and fibrosis. As such, it has the potential to favorably impact the health and lives of millions of patients around the globe.”

Quality of sleep link to fatty liver disease

Quality of sleep link to fatty liver disease

A July 2022 study by the Guangdong Provincial Key Laboratory of Food, Nutrition and Health and Sun Yat-sen University in Guangzhou, China said,  “People with poor nighttime sleep and prolonged daytime napping have the highest risk for developing fatty liver disease,”  and “Our study found a moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease.”

Poor “sleep hygiene” included

  • late bedtime

  • snoring

  • daytime napping for over 30 minutes

“Our study provides evidence that even a moderate improvement in sleep quality is sufficient to reduce the risk for fatty liver disease, especially in those with unhealthy lifestyles,” 

“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality.”

sucrose and high fructose corn syrup and health risks

sucrose and high fructose corn syrup and health risks

An August 2021 study by University of California, Davis, said,

  • “This is the first dietary intervention study to show that consumption of both sucrose- and high fructose corn-sweetened beverages increase liver fat and decrease insulin sensitivity,” 

  • “People often have a skewed perspective of aspartame and give sucrose a pass, but this study suggests that consumers should be equally concerned about both major added sugars in our food supply.”

  • “Within the span of two weeks, we observed a significant change in liver fat and insulin sensitivity in the two groups consuming sucrose- or high fructose corn syrup-sweetened beverages,” 

  • “That’s concerning because the prevalence of fatty liver [nonalcoholic fatty liver disease] and Type 2 diabetes continues to increase globally.”

  • “It’s all physiologically connected, although we’re not sure [in what] direction it goes,” 

  • “It’s very likely that the mechanism by which we develop metabolic syndrome goes through liver fat and insulin resistance. An increase in liver fat can be benign for a certain amount of time and for certain people. But it can also progress to associated inflammation in liver cells that causes fibrosis and negatively impacts liver function, which can make an individual more prone to liver cancer.”

high fructose corn syrup and fatty liver disease

high fructose corn syrup and fatty liver disease

A June 2022 report by University in Los Angeles, California said, 

  • “NAFLD [non-alcoholic fatty liver disease] is a serious problem and it is increasing in the population. There is a racial/ethnic difference in the prevalence of the NAFLD. People consume high-fructose corn syrup in foods, soft drinks and other beverages. Some studies suggested that consumption of high-fructose corn syrup is related to the development of NAFLD,”

  • “We found that when adjusting for the demographics and behavioral factors (smoking, modest alcohol consumption, diet quality and physical activity), high fructose consumption was associated with a higher chance of NAFLD among the total population and Mexican Americans,”

  • “High fructose consumption in Mexican Americans contributed, in part, to the health disparity of NAFLD,”

Diabetes type 2: New Treatment pathway

Diabetes type 2: New Treatment pathway

A June 2021 study from University of Arizona College of Agriculture and Life Sciences and BIO5 Institute, and  Washington University in St. Louis, the University of Pennsylvania and Northwestern University,

  • "All current therapeutics for Type 2 diabetes primarily aim to decrease blood glucose. So, they are treating a symptom, much like treating the flu by decreasing the fever,”

  • "Obesity is known to be a cause of Type 2 diabetes and, for a long time, we have known that the amount of fat in the liver increases with obesity,”

  • "As fat increases in the liver, the incidence of diabetes increases."

  • "We found that fat in the liver increased the release of the inhibitory neurotransmitter Gamma-aminobutyric acid, or GABA," 

  • "We then identified the pathway by which GABA synthesis was occurring and the key enzyme that is responsible for liver GABA production - GABA transaminase."

  • "When the liver produces GABA, it decreases activity of those nerves that run from the liver to the brain. Thus, fatty liver, by producing GABA, is decreasing firing activity to the brain," 

  • "That decrease in firing is sensed by the central nervous system, which changes outgoing signals that affect glucose homeostasis."

  • "Inhibition of excess liver GABA production restored insulin sensitivity within days," 

  • "Longer term inhibition of GABA-transaminase resulted in decreased food intake and weight loss."

Non-alcoholic liver disease

Non-alcoholic liver disease

A July 2021 study by Helmholtz Diabetes Center at Helmholtz Zentrum München said

  • "Understanding the mechanism by which this condition becomes life threatening is key in our quest for the discovery of therapeutic solutions and preventative measures,”

  • "Our results demonstrated that during progression to non-alcoholic steatohepatitis, hepatocytes suffer from partial identity loss, they are re-programmed," 

  • "These findings are important because they unravel the cellular mechanisms underlying non-alcoholic steatohepatitis. Knowing about the role of the protein networks and the identity loss of hepatocytes gives us potential intervention targets for the development of effective therapies"

Probiotic Lactobacillus acidophilus and inflammatory bowel disease

Probiotic Lactobacillus acidophilus and inflammatory bowel disease

An April 2021 study by Penn State College of Medicine, Hershey Medical Center said,

"Our data indicate that [Lactobacillus acidophilus] is able to prevent colonic inflammation formation and promote colitis healing,”

"The implications of the present findings are that this bacterial strain can be used in a wide variety of intestinal permeability disorders, including IBD [inflammatory bowel disease], coeliac disease, alcoholic liver disease, non-alcoholic fatty liver disease, and necrotizing enterocolitis, to treat inflammation associated with the leaky gut.”

Itching and Liver Disease

Itching and Liver Disease

An April 2021 study by Duke School of Medicine and Wake Forest University and researchers in Mexico, Poland, Germany said,

"The skin cells themselves are sensory under certain conditions, specifically the outermost layer of cells, the keratinocytes,"

"The initial ideas were that it plays a role in how the skin is layered, and in skin barrier function,”

"But this current research is getting us into a more exciting territory of the skin actually moonlighting as a sensory organ.”

"If the itch comes up in PBC, it's so debilitating that the patients might need a new liver. That's how bad it can get,"

Fatty Liver Disease

Fatty Liver Disease

Fatty Li ver Disease has genetic and nutritional components.

The NHS says, 

“Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese.”

“A healthy liver should contain little or no fat. It's estimated up to 1 in every 3 people in the UK has early stages of NAFLD, where there are small amounts of fat in their liver.”

“There's currently no specific medication for NAFLD, but making healthy lifestyle choices can help.”

Advances in the study of NAFLD have used a chimeric mouse, one that contains both normal cells and genetically manipulated.

An April 2021 study (on mice) by Baylor College of Medicine and Duke University of NAFLD said,

"NAFLD has been difficult to study mainly because we had no good animal model," 

"Our goal was to have a mouse model that would allow us to study the disorder and test potential treatments," 

"Applying our lab's years long expertise developing chimeric mouse models, those that combine both human and murine cells, we developed mice with livers that were part human and part murine."

"We were surprised by the striking differences we observed under the microscope,”

"In the same liver, the human liver cells were filled with fat, a typical characteristic of the human disease, while the mouse liver cells remained normal."

"For instance, when mice that received human liver cells fed on a high-fat diet, they started to show features of cholesterol metabolism that looked more like what a patient shows than what other previous animal models showed," 

"We made the same observation regarding genes that are regulated after the high-fat diet. All the analyses pointed at cholesterol metabolism being changed in this model in a way that closely replicates what we see in humans."

"We discovered that, compared to the normal mouse liver cells in our model, the fat-laden human liver cells had higher levels of gene transcripts for enzymes involved in cholesterol synthesis," 

"We wanted to see whether this was also the case in human NAFLD livers."

"Using the NAFLD consensome (1) we discovered that, indeed, compared to normal livers, NAFLD livers have consistently higher levels of cholesterol synthesis enzyme transcripts,”

"This is additional confirmation of the clinical accuracy of our NAFLD model."

"Here we have a model in which human liver cells respond like in humans. We propose that this model can be used to better understand NAFLD and to identify effective therapies."


Notes 

  1. consensome:

The Signaling Pathways Project, an integrated 'omics knowledgebase for mammalian cellular signaling pathways.
Scientific Data, 31 Oct 2019, 6(1):252
DOI: 10.1038/s41597-019-0193-4 PMID: 31672983 PMCID: PMC6823428

“the Signaling Pathways Project (SPP), which incorporates community classifications of signaling pathway nodes (receptors, enzymes, transcription factors and co-nodes) and their cognate bioactive small molecules.

We then mapped over 10,000 public transcriptomic or cistromic experiments to their pathway node or biosample of study.

To enable prediction of pathway node-gene target transcriptional regulatory relationships through SPP, we generated consensus 'omics signatures, or consensomes, which ranked genes based on measures of their significant differential expression or promoter occupancy across transcriptomic or cistromic experiments mapped to a specific node family.

Consensomes were validated using alignment with canonical literature knowledge, gene target-level integration of transcriptomic and cistromic data points, and in bench experiments confirming previously uncharacterized node-gene target regulatory relationships.”

fat distribution in the liver

fat distribution in the liver

A March 2021 study on nonalcoholic fatty liver disease by Tokyo University of Science found,

"Lipid distribution in the liver provides crucial information for diagnosing fatty liver-associated liver diseases including cancer, and therefore, a noninvasive, label-free, quantitative modality is needed."

"We have developed a method to visualize the distribution of lipids in the liver using a near-infrared spectral imaging technique that incorporates machine learning." 

"the ultimate goal of this collaborative research is to differentiate and identify fatty acids in the liver." 


metabolic pathways and disease

metabolic pathways and disease

A March 2021 study headed up by Dr. Claudia Langenberg, looked at a number of unassociated metabolic processes linked to various diseases.

"We wanted to know whether there are certain markers in the blood that indicate a risk, not only for one but for several diseases at the same time," 

"We found, for example, that an increased concentration of the sugar-like molecule N-acetylneuraminate increased the risk of no less than 14 diseases," 

"Gamma-glutamylglycine, on the other hand, is exclusively associated with the occurrence of diabetes. Other members of the same molecular groups simultaneously increase the risk of liver and heart disease." 

"Overall, we observed that two-thirds of the molecules are associated with the occurrence of more than one disease. This is in line with the fact that patients often develop a range of diseases in the course of their lives. If we succeed in influencing these key factors, this could make it possible to counter multiple diseases simultaneously."


The Liver, high blood sugar and muscle loss

The Liver, high blood sugar and muscle loss

A March 2021 study by Monash University said, 

"The ageing-related diseases of skeletal muscle loss and type 2 diabetes are very prevalent and are a huge societal and economic burden. We have known for some time that the ageing-related diseases of skeletal muscle loss and type 2 diabetes were linked but we didn't know how.”

"Our studies demonstrate that the liver is a critical control point for muscle protein metabolism; a discovery that is quite surprising. We believe that our new findings highlight the need to examine the role of skeletal muscle atrophy in type 2 diabetes more closely in human clinical populations."

The role of added sugar in fat production

The role of added sugar in fat production

A March 2021 study by the University of Zurich found, 

"Eighty grams of sugar daily, which is equivalent to about 0.8 liters of a normal soft drink, boosts fat production in the liver. And the overactive fat production continues for a longer period of time, even if no more sugar is consumed,"

"The body's own fat production in the liver was twice as high in the fructose group as in the glucose group or the control group - and this was still the case more than twelve hours after the last meal or sugar consumption,”

Chronobiology, the liver, circadian rhythms and position

Chronobiology, the liver, circadian rhythms and position

A new January 2021 study by the Ecole Polytechnique Federale de Lausane in the field of chronobiology sees Western medicine finding the first steps on its way towards a concept known for many hundreds of years in the field of Chinese Medicine as to time and the organs of the body. And in Unani Tibb medicine regarding time and position of the liver.

The study found that, “many of the liver's genes seem to be both zonated and rhythmic, meaning that they are regulated by both their location in the liver and the time of the day. These dually regulated genes are mostly linked to key functions of the liver, e.g. the metabolism of lipids, carbohydrates, and amino acids,”

"The work reveals a richness of space-time gene expression dynamics of the liver, and shows how compartmentalization of liver function in both space and time is hallmark of metabolic activity in the mammalian liver,"

Chinese Medicine: Mothers

Chinese Medicine: Mothers

“The Blood is the Mother of Qi.”

“The Kidney is the Mother of the Liver.”

Such statements from Chinese Medicine theory seem at odds with current Western Medicine theory (and practice).  But the approach in Chinese Medicine is altogether more holistic, systemic and interrelated.