Tag: fatty acids

Categories : Obstetrics & GynaecologyTags :

Fatty Acids in Umbilical Cord Blood Might Cause Autism Spectrum Disorder

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Scientists unveil the link between cord blood fatty acid metabolites and autism spectrum disorder symptoms in children

Source: Pixabay CC0

Autism spectrum disorder (ASD) is quite prevalent, but its underlying mechanism is not well understood. In a recent study, researchers from Japan have found a significant link between the levels of specific dihydroxy fatty acids in umbilical cord blood and ASD symptoms. Their findings, published in Psychiatry and Clinical Neurosciences, highlight the role of these metabolites in the developmental trajectory of ASD and could pave the way for early diagnostic techniques and a better understanding of ASD pathophysiology.

Although the exact causes of ASD are unclear, currently available evidence points to neuroinflammation as a major factor. Several studies in mouse models of ASD have hinted at the importance of polyunsaturated fatty acids (PUFA) and their metabolites during pregnancy in playing a key role in ASD development. PUFA metabolites regulated by the cytochrome P450 (CYP) affect foetal development in mice causing impairments closely linked to ASD symptoms. However, it is still unclear if the same is true for humans and needs further investigation.

To address this knowledge gap, a research team led by Professor Hideo Matsuzaki from the Research Center for Child Mental Development, analysed the CYP-PUFA levels in neonatal umbilical cord blood samples. Their study,  sheds light on the possible causes of ASD.

Sharing the motivation behind their study, Prof. Matsuzaki explains, “CYP metabolism forms both epoxy fatty acids (EpFAs), which have anti-inflammatory effects, and dihydroxy fatty acids, or ‘diols,’ which have inflammatory properties. We hypothesized that the dynamics of CYP-PUFA metabolites during the fetal period, that is, lower EpFA levels, higher diol levels, and/or increased EpFA metabolic enzymes would influence ASD symptoms and difficulties with daily functioning in children after birth.”

To test this hypothesis, the researchers investigated the link between PUFA metabolites in umbilical cord blood and ASD scores in 200 children. The cord blood samples had been collected immediately after birth and preserved appropriately, whereas ASD symptoms and adaptive functioning were assessed when the same children were six years old, with the help of their mothers.

After careful statistical analyses of the results, the researchers identified one compound in cord blood that may have strong implications for ASD severity, namely 11,12- dihydroxyeicosatrienoic acids (diHETrE), a dihydroxy fatty acid derived from arachidonic acid. This fatty acid is found in poultry, animal organs and meat, fish, seafood, and eggs.

“The levels of diHETrE, an arachidonic acid-derived diol, in cord blood at birth significantly impacted subsequent ASD symptoms in children and were also associated with impaired adaptive functioning. These findings suggest that the dynamics of diHETrE during the foetal period is important in the developmental trajectory of children after birth,” highlights Prof Matsuzaki.

More specifically, the researchers found that higher levels of the molecule 11,12-diHETrE had an impact on social interactions, whereas low levels of 8,9-diHETrE impacted repetitive and restrictive behaviours. Moreover, this correlation was more specific for girls than for boys. This newfound knowledge could be crucial in understanding, diagnosing, and potentially preventing ASD. By measuring diHETrE levels at birth, it may be possible to predict the likelihood of ASD development in children.

“The effectiveness of early intervention for children with ASD is well established and detecting it at birth could enhance intervention and support for children with ASD,” muses Prof Matsuzaki. He also adds that inhibiting diHETrE metabolism during pregnancy might be a promising avenue for preventing ASD traits in children, although more research will be needed in this regard.

In conclusion, these findings open a promising avenue for researchers unravelling the mysteries surrounding ASD. We hope that enhanced understanding and early diagnostics will be able to improve the lives of people with ASD and their families.

Source: University of Fukui

Categories : Cancer Diet and NutritionTags :

New Study Finds that Fatty Acid in Beef, Lamb and Dairy Boosts Cancer-fighting T Cells

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Photo by Jose Ignacio Pompe on Unsplash

Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumours and kill cancer cells, according to a new study by researchers from the University of Chicago.

The research, published in Nature, also shows that cancer patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting potential as a nutritional complement to conventional cancer therapy. Although trans fatty acids that are industrially produced are known to be harmful to health, natural ones such as TVA are linked to health benefits. But the researchers don’t envision prescribing diets packed with red meat and cheese – rather, TVA would be a supplement.

“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, professor of medicine at UChicago and one of the senior authors. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumour immunity by activating an important immune pathway.”

Searching for nutrients that activate immune cells

Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, they started with a database of around 700 known metabolites that come from food and assembled a ‘blood nutrient’ compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumour immunity by activating CD8+ T cells, which are critical for killing cancerous or virally infected cells.

After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.

Feeding mice a diet enriched with TVA significantly reduced the tumour growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumours.

The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, professor of chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumour fighting ability.

Finally, working with other researchers, the team analysed blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested leukaemia cell lines and saw that TVA enhanced the ability of an immunotherapy drug to kill leukaemia cells.

TVA as a supplement

The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimised amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.

“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.

‘The new research also highlights the promise of this ‘metabolomic’ approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level — I find that really amazing and intriguing.”

Source: University of Chicago

Categories : Cardiovascular DiseaseTags :

High Fat Dairy Intake not Tied to CVD Risk

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Photo by Waldemar Brandt on Unsplash

In a study of countries with high dairy consumption, higher intakes of dairy fat, as measured by bloodstream levels of fatty acids, had a lower risk of cardiovascular disease (CVD) compared to those with low intakes. Higher intakes of dairy fat were not linked to an increased mortality risk.

In a study published in PLoS Medicine, researchers combined results from 4000 Swedish adults with those from 17 similar studies in other countries, creating the most comprehensive evidence to date on the relationship between this more objective measure of dairy fat consumption, risk of  and death.

Dr Matti Marklund from The George Institute for Global Health, Johns Hopkins Bloomberg School of Public Health, and Uppsala University said that with rising dairy consumption around the world, a better understanding of the health impact was needed.

“Many studies have relied on people being able to remember and record the amounts and types of dairy foods they’ve eaten, which is especially difficult given that dairy is commonly used in a variety of foods.

“Instead, we measured blood levels of certain fatty acids, or fat ‘building blocks’ that are found in dairy foods, which gives a more objective measure of dairy fat intake that doesn’t rely on memory or the quality of food databases,” he added.

“We found those with the highest levels actually had the lowest risk of CVD. These relationships are highly interesting, but we need further studies to better understand the full health impact of dairy fats and dairy foods.”

Sweden has one of the world’s highest consumption of dairy. An international team of researchers assessed dairy fat consumption in 4150 Swedish 60-year-olds by measuring blood levels of a particular fatty acid that is mainly found in dairy foods and therefore can be used to reflect intake of dairy fat.

The participants were then followed up for an average of 16 years, recording heart attacks, strokes and other serious circulatory events, and all cause mortality.

After adjustment for other known CVD risk factors including things like age, income, lifestyle, dietary habits, and other diseases, the CVD risk was lowest for those with high levels of the fatty acid (which reflects a high intake of dairy fats). Those with the highest levels had no increased all-cause mortality risk.

These findings highlight the uncertainty of evidence in this area, which is reflected in dietary guidelines, noted  Dr Marklund.

“While some dietary guidelines continue to suggest consumers choose low-fat dairy products, others have moved away from that advice, instead suggesting dairy can be part of a healthy diet with an  emphasis on selecting certain dairy foods — for example, yoghurt rather than butter — or avoiding sweetened dairy products that are loaded with added sugar,” he said.

Combining these results with 17 other studies with a total of almost 43 000 participants from the US, Denmark, and the UK confirmed these findings in other populations.

“While the findings may be partly influenced by factors other than dairy fat, our study does not suggest any harm of dairy fat per se,” Dr. Marklund said.

Lead author Dr Kathy Trieu from The George Institute for Global Health pointed out that consumption of some dairy products, especially fermented products, have been shown to be linked to cardiovascular benefits.

“Increasing evidence suggests that the health impact of dairy foods may be more dependent on the type — such as cheese, yoghurt, milk, and butter — rather than the fat content, which has raised doubts if avoidance of dairy fats overall is beneficial for cardiovascular health,” she said.

“Our study suggests that cutting down on dairy fat or avoiding dairy altogether might not be the best choice for heart health.”

“It is important to remember that although dairy foods can be rich in saturated fat, they are also rich in many other nutrients and can be a part of a healthy diet. However, other fats like those found in seafood, nuts, and non-tropical vegetable oils can have greater health benefits than dairy fats,” Dr Trieu added.

Source: The George Institute for Global Health