Glutamine could help people with obesity reduce fat mass and inflammation

Glutamine could help people with obesity reduce fat mass and inflammation

Glutamine could help people with obesity reduce fat mass and inflammation

Lower glutamine-levels were also associated with larger fat cell size and higher body fat percentage independently of body-mass index (BMI), according to the study.

#glutamine #leanmass #inflammation

”Glutamine links obesity to inflammation in human white adipose tissue,” Paul Petrus, Simon Lecoutre, Lucile Dollet, Clotilde Wiel, André Sulen, Hui Gao, Beatriz Tavira, Jurga Laurencikiene, Olav Rooyackers, Antonio Checa, Iyadh Douagi, Craig E. Wheelock, Peter Arner, Mark McCarthy, Martin O. Bergo, Laurienne Edgar, Robin P. Choudhury, Myriam Aouadi, Anna Krookand Mikael Rydén, Cell Metabolism, online December 19, 2019. https://doi.org/10.1016/j.cmet.2019.11.019

‘Memories’ pass between generations

By James Gallagher Health and science reporter, BBC News

Generations of a family

 

Behaviour can be affected by events in previous generations which have been passed on through a form of genetic memory, animal studies suggest.

Experiments showed that a traumatic event could affect the DNA in sperm and alter the brains and behaviour of subsequent generations.

A Nature Neuroscience study shows mice trained to avoid a smell passed their aversion on to their “grandchildren”.

Continue reading “‘Memories’ pass between generations”

Folic acid deficiency can affect the health of great, great grandchildren

Contact: Genevieve Maul gm349@admin.cam.ac.uk 44-012-237-65542 University of Cambridge

Deficiencies associated with spina bifida, heart defects and placental abnormalities

Folic acid deficiency can cause severe health problems in offspring, including spina bifida, heart defects and placental abnormalities. A study out today reveals that a mutation in a gene necessary for the metabolism of folic acid not only impacts the immediate offspring but can also have detrimental health effects on the next several generations. The new research, which also sheds light on the molecular mechanism of folic acid (also known as folate) during development, was published today in the journal Cell.

“Although our research focused on genetic mutations which disrupts the break down and metabolism of folic acid, we believe that folic acid deficiency in the diet would have a similar multi-generational impact on health,” said Dr Erica Watson from the Centre for Trophoblast Research at the University of Cambridge, who led the study.

The detrimental effects of folic acid deficiency on development are quite well known. As a result, many countries, to include Canada and the US, have implemented folate fortification programmes which require folic acid to be added to cereal products. However, until now, very little was known about how folic acid deficiency caused the diverse range of health problems in offspring.

“Fortification programmes have reduced the risk of health effects but not eliminated them completely,” said Dr Watson. “Based on our research, we now believe that it may take more than one generation to eliminate the health problems caused by folate deficiency.”

The researchers, from the Universities of Cambridge and Calgary, used mice for the study as they metabolize folic acid very similarly to humans and because folic acid deficiency or mutations in the same genes required to break down folic acid in humans result in similar developmental abnormalities and diseases in mice. This enabled the researchers to explore how the molecular mechanism of folic acid deficiency impacted development, thereby causing health problems.

For the study, the scientists used mice in which a gene called Mtrr was specifically mutated. The gene is key to the normal progression of the folic acid cycle and, when mutated, it results in abnormal folic acid metabolism causing similar effects to dietary folic acid deficiency. The researchers found that when either the maternal grandmother or the maternal grandfather had this Mtrr mutation, their genetically normal grandchildren were at risk of a wide spectrum of developmental abnormalities. These developmental abnormalities were also seen in the fourth and fifth generations of mice.

Through another experiment which involved transferring the embryo from the third generation into a normal healthy female mouse, they discovered that these developmental abnormalities were not passed down genetically. Instead, the serious defects were the result of epigenetic changes which had been inherited.

Epigenetics is a system which turns genes on and off. It occurs when chemicals, such as methyl groups, bind to the DNA at specific locations to control which genes are expressed and when they are expressed. (Interestingly, the folic acid cycle is required to make sure that the cell has enough methyl groups for normal gene expression.) Epigenetic inheritance refers to the passing of these epigenetic marks from one generation to the next – despite the epigenome, for the most part, being ‘wiped clean’ after each generation.

The researchers hypothesize that, for a yet unknown reason, some of these abnormal epigenetic marks caused by the Mtrr mutation may escape this normal erasure and are inherited by the next generation. If these abnormal epigenetic marks that regulate genes important for development are inherited, then these generations may develop abnormalities as a result of the wrong genes being turned on or off.

“It surprised us to find that the great, great grandchildren of a parent who has had a folic acid deficiency could have health problems as a result – suggesting that the ‘sins of your maternal grandparents’ can have an effect on your development and your risk for disease,” said Dr Watson.

“More importantly, our research shows that disease in general can be inherited through epigenetic means rather than genetic means, which has huge implications for human health. Environmental factors that influence epigenetic patterns – e.g., diet, epigenetic disruptors in the environment such as chemicals, etc. – may also have long term, multigenerational effects.”

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For additional information please contact:

Genevieve Maul, Office of Communications, University of Cambridge Tel: direct, +44 (0) 1223 765542, +44 (0) 1223 332300 Mob: +44 (0) 7774 017464 Email: Genevieve.maul@admin.cam.ac.uk

Notes to editors:

  • The paper ‘Mutation in Folate Metabolism Causes Epigenetic Instability and Transgenerational Effects On Development’ will be published in the 26 September edition of Cell

     

  • Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge 

     

  • To view a video of the researchers explaining their study, please go to: http://www.youtube.com/watch?v=Dlfg49sjo3U

100 reasons to change the way we think about genetics : Epigenetic inheritance passed down through generations not all through DNA

2009 study posted for filing

Contact: Kevin Stacey
kstacey@press.uchicago.edu
773-834-0386
University of Chicago Press Journals

Article reviews evidence for epigenetic inheritance in wide range of species

For years, genes have been considered the one and only way biological traits could be passed down through generations of organisms.

Not anymore.

Increasingly, biologists are finding that non-genetic variation acquired during the life of an organism can sometimes be passed on to offspring—a phenomenon known as epigenetic inheritance. An article forthcoming in the July issue of The Quarterly Review of Biology lists over 100 well-documented cases of epigenetic inheritance between generations of organisms, and suggests that non-DNA inheritance happens much more often than scientists previously thought.

Biologists have suspected for years that some kind of epigenetic inheritance occurs at the cellular level. The different kinds of cells in our bodies provide an example. Skin cells and brain cells have different forms and functions, despite having exactly the same DNA. There must be mechanisms—other than DNA—that make sure skin cells stay skin cells when they divide.

Only recently, however, have researchers begun to find molecular evidence of non-DNA inheritance between organisms as well as between cells. The main question now is: How often does it happen?

“The analysis of these data shows that epigenetic inheritance is ubiquitous …,” write Eva Jablonka and Gal Raz, both of Tel-Aviv University in Israel. Their article outlines inherited epigenetic variation in bacteria, protists, fungi, plants, and animals.

These findings “represent the tip of a very large iceberg,” the authors say.

For example, Jablonka and Raz cite a study finding that when fruit flies are exposed to certain chemicals, at least 13 generations of their descendants are born with bristly outgrowths on their eyes. Another study found that exposing a pregnant rat to a chemical that alters reproductive hormones leads to generations of sick offspring. Yet another study shows higher rates of heart disease and diabetes in the children and grandchildren of people who were malnourished in adolescence.

In these cases, as well as the rest of the cases Jablonka and Raz cite, the source of the variation in subsequent generations was not DNA. Rather, the new traits were carried on through epigenetic means.

There are four known mechanisms for epigenetic inheritance. According to Jablonka and Raz, the best understood of these is “DNA methylation.” Methyls, small chemical groups within cells, latch on to certain areas along the DNA strand. The methyls serve as a kind of switch that renders genes active or inactive.

By turning genes on and off, methyls can have a profound impact on the form and function of cells and organisms, without changing the underlying DNA. If the normal pattern of methyls is altered—by a chemical agent, for example—that new pattern can be passed to future generations.

The result, as in the case of the pregnant rats, can be dramatic and stick around for generations, despite the fact that underlying DNA remains unchanged.

LAMARCK REVISITED

New evidence for epigenetic inheritance has profound implications for the study of evolution, Jablonka and Raz say.

“Incorporating epigenetic inheritance into evolutionary theory extends the scope of evolutionary thinking and leads to notions of heredity and evolution that incorporate development,” they write.

This is a vindication of sorts for 18th century naturalist Jean Baptiste Lamarck. Lamarck, whose writings on evolution predated Charles Darwin’s, believed that evolution was driven in part by the inheritance of acquired traits. His classic example was the giraffe. Giraffe ancestors, Lamarck surmised, reached with their necks to munch leaves high in trees. The reaching caused their necks to become slightly longer—a trait that was passed on to descendants. Generation after generation inherited slightly longer necks, and the result is what we see in giraffes today.

With the advent of Mendelian genetics and the later discovery of DNA, Lamarck’s ideas fell out of favor entirely. Research on epigenetics, while yet to uncover anything as dramatic as Lamarck’s giraffes, does suggest that acquired traits can be heritable, and that Lamarck was not so wrong after all.

 

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Eva Jablonka and Gal Raz, “Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution,” The Quarterly Review of Biology, June 2009. http://www.journals.uchicago.edu/toc/qrb/current.

The premier review journal in biology since 1926, The Quarterly Review of Biology publishes articles in all areas of biology but with a traditional emphasis on evolution, ecology, and organismal biology. QRB papers do not merely summarize a topic, but offer important new ideas, concepts, and syntheses. They often shape the course of future research within a field. In addition, the book review section of the QRB is the most comprehensive in biology.

Dioxin Causes Disease and Reproductive Problems Across Generations, Study Finds

Even if all the dioxin were eliminated from the planet, researchers say its legacy will live on in the way it turns genes on and off in the descendants of people exposed over the past half century. (Credit: iStockphoto/Dmitry Oshchepkov)

ScienceDaily (Sep. 26, 2012) — Since the 1960s, when the defoliant Agent Orange was widely used in Vietnam, military, industry and environmental groups have debated the toxicity of one of its ingredients, the chemical dioxin, and how it should be regulated.

But even if all the dioxin were eliminated from the planet, Washington State University researchers say its legacy would live on in the way it turns genes on and off in the descendants of people exposed over the past half century.

Writing in the journal PLoS ONE, biologist Michael Skinner and members of his lab say dioxin administered to pregnant rats resulted in a variety of reproductive problems and disease in subsequent generations. The first generation of rats had prostate disease, polycystic ovarian disease and fewer ovarian follicles, the structures that contain eggs. To the surprise of Skinner and his colleagues, the third generation had even more dramatic incidences of ovarian disease and, in males, kidney disease.

“Therefore, it is not just the individuals exposed, but potentially the great-grandchildren that may experience increased adult-onset disease susceptibility,” says Skinner.

Skinner is a professor of reproductive biology and environmental epigenetics — the process in which environmental factors affect how genes are turned on and off in the offspring of an exposed animal, even though its DNA sequences remain unchanged. In this year alone, Skinner and colleagues have published studies finding epigenetic diseases promoted by jet fuel and other hydrocarbon mixtures, plastics, pesticides and fungicides, as well as dioxin.

The field of epigenetics opens new ground in the study of how diseases and reproductive problems develop. While toxicologists generally focus on animals exposed to a compound, work in Skinner’s lab further demonstrates that diseases can also stem from older, ancestral exposures that are then mediated through epigenetic changes in sperm.

This latest study was funded by the U.S. Department of Defense, the National Institutes of Health and the National Institute of Environmental Health Sciences. Skinner designed the study; the research was done by Assistant Research Professor Mohan Manikkam, Research Technician Rebecca Tracey and Post-doctoral Researcher Carlos Guerrero-Bosagna

Environmental toxicants causing ovarian disease across generations

Contact: Michael Skinner skinner@wsu.edu 509-335-1524 Washington State University

WSU researchers expand research on environmental epigenetics and ovarian disease

PULLMAN, Wash.—Washington State University researchers have found that ovarian disease can result from exposures to a wide range of environmental chemicals and be inherited by future generations.

WSU reproductive biologist Michael Skinner and his laboratory colleagues looked at how a fungicide, pesticide, plastic, dioxin and hydrocarbon mixtures affected a gestating rat’s progeny for multiple generations.   They saw subsequent generations inherit ovarian disease by “epigenetic transgenerational inheritance.” Epigenetics regulates how genes are turned on and off in tissues and cells. Three generations were affected, showing fewer ovarian follicles—the source of eggs—and increased polycystic ovarian disease.

The findings suggest ancestral environmental exposures and epigenetics may be a significant added factor in the development of ovarian disease, says Skinner.

“What your great grandmother was exposed to when she was pregnant may promote ovarian disease in you and you’re going to pass it on to your grandchildren,” he says.  “Ovarian disease has been increasing over the past few decades to effect more than 10 percent of the human female population and environmental epigenetics may provide a reason for this increase.”

The research appears in the current issue of the online journal PLoS ONE. It marks the first time researchers have shown that a number of different classes of environmental toxicants can promote the epigenetic inheritance of ovarian disease across multiple generations.

Research by Skinner and colleagues published earlier this year in PLoS ONE showed jet fuel, dioxin, plastics, and the pesticides DEET and permethrin can also promote epigenetic inheritance of disease in young adults across generations.

The work is a departure from traditional studies on several fronts. Where most genetic work looks at genes as the ultimate arbiters of inheritance, Skinner’s lab has repeatedly shown the impact of the environmental epigenetics on how those genes are regulated.  The field is already changing how one might look at toxicology, public health and biology in general.

The new study, says Skinner, provides a proof of concept that ancestral environmental exposures and environmental epigenetics promote ovarian disease and can be used to further diagnose exposure to toxicants and their subsequent health impacts. It also opens the door to using epigenetic molecular markers to diagnose ovarian disease before it occurs so new therapies could be developed.

In a broader sense, the study shows how epigenetics can have a significant role in disease development and life itself.

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The paper, “Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease,” can be viewed at http://dx.plos.org/10.1371/journal.pone.0036129