Stress during pregnancy leads to abdominal obesity in mice offspring

ScienceDaily (July 31, 2012) — New research suggests that the neuropeptide Y in plasma and its Y2 receptor in visceral fat play an important role in obesity.

See Also:Health & MedicineObesityDiet and Weight LossStaying HealthyMind & BrainDieting and Weight ControlNutrition ResearchStressReferenceAppetiteNutrition and pregnancyGeneral fitness trainingDiabetes mellitus type 2

A new report involving mice suggests that a relationship exists between maternal metabolic or psychological stress and the development of obesity, type 2 diabetes, and metabolic syndrome in her offspring. What's more, the report shows that if the stress cannot be reduced or eliminated, manipulating the neuropeptide Y (NPY) system in visceral fat may prevent maternal stress-induced obesity from occurring in the next generation. This discovery is reported in the August 2012 issue of The FASEB Journal.

"Obesity is a worldwide disease. Here we found that maternal stress, psychologically and metabolically, increases abdominal obesity and glucose intolerance in the next generation in a sex-specific manner, which is mediated by the NPY system in visceral fat," said Ruijun Han, a researcher involved in the work from the Department of Integrative Biology and Physiology, Stress Physiology Center at the University of Minnesota. "Our study suggested that NPY in the platelet-rich plasma and its Y2 receptor in the visceral fat, play an important role in maternal stress-programmed abdominal obesity and metabolic syndrome in offspring."

To make this discovery, Young and colleagues fed different groups of pregnant mice a low protein diet during pregnancy and lactation; a normal protein diet during pregnancy and lactation; or a low protein diet only during pregnancy. After weaning, all the pups were fed high fat diets for 18 weeks, and metabolic parameters and expression of NPY system in periphery tissues were monitored and measured.

"There are a lot of reasons why expectant mothers should not be under stress," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "and this report adds yet another reason. What's most interesting, however, is that it provides some insight into how we can counter the negative effects of stress, even when it's not possible to reduce or eliminate the stressors themselves."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article

How malnutrition leads to inflamed intestines

ScienceDaily (July 24, 2012) — More than one billion people in poor countries are starving, and malnutrition remains a major problem even in rich countries, making it a leading cause of death in the world. For over a hundred years, doctors have known that a lack of protein in the diet or low levels of amino acids, the building blocks of proteins, can lead to symptoms like diarrhoea, inflamed intestines and other immune system disorders, which weaken the body and can be fatal. However, the molecular mechanism which explains how malnutrition causes such severe symptoms has been largely unexplored.

Now a research group led by Josef Penninger, the director of the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria, in cooperation with Philip Rosenstiel, University of Kiel, Germany, has found a molecular explanation for the increased susceptibility to intestinal inflammation in malnutrition.  The researchers were studying an enzyme which helps to control blood pressure, kidney failure in diabetes, heart failure and lung injury, called the Angiotensin Converting Enzyme 2, or ACE2.  This enzyme was identified as the key receptor for SARS virus infections, but the researchers also discovered an entirely new function.  ACE2 controls the way our intestines take in amino acids from our food, via amino acid transporters, and in particular the uptake of the essential amino acid tryptophan.

Too little tryptophan alters our natural immune system, which changes the types of bacteria which can live in our bowels and guts, leading to higher sensitivity and eventually diarrhoea and inflamed intestines.  Increasing the intake of tryptophan in their diet provided relief for mice suffering from intestinal inflammation. The mixture of bacteria returned to normal, the inflammation died down, and the mice also became less susceptible to new attacks.

"The research shows how the food we eat can directly change the good bacteria in our intestines to bad bacteria and so influence our health”, says Thomas Perlot, the first author of the study. “Our results might also explain nutritional effects that have been known for centuries and provide a molecular link between malnutrition and the bacteria living in our intestines. This discovery could be used in the future to treat patients with a simple regulated diet or by taking tryptophan as a food supplement.  And there is hardly any risk of side effects from artificially increasing an amino acid found in the normal diet.”

Josef Penninger, the lead author, says “I have studied ACE2 for more than 10 years and was completely stunned by this novel link between ACE2 and amino acid balance in the gut. Biology continues to surprise me. Up to a billion people in the world are malnourished, especially the poor and disadvantaged. In Austria alone, around 80,000 people suffer from a chronic inflammatory bowel disease like ulcerative colitis or Crohn's disease. I hope that our findings have opened a door to a better molecular understanding how malnutrition affects human health. Whether simple tryptophan diets can indeed cure the effects of malnutrition in humans now needs to be carefully tested in clinical trials.”

Share This:See Also:Health & MedicineGastrointestinal ProblemsDietary SupplementNutritionDiet and Weight LossCholesterolDiabetesReferenceInflammation of the kidneyNeurotransmitterHeat shock proteinInflammationShare this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article

How malnutrition leads to inflamed intestines

ScienceDaily (July 24, 2012) — More than one billion people in poor countries are starving, and malnutrition remains a major problem even in rich countries, making it a leading cause of death in the world. For over a hundred years, doctors have known that a lack of protein in the diet or low levels of amino acids, the building blocks of proteins, can lead to symptoms like diarrhoea, inflamed intestines and other immune system disorders, which weaken the body and can be fatal. However, the molecular mechanism which explains how malnutrition causes such severe symptoms has been largely unexplored.

Now a research group led by Josef Penninger, the director of the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria, in cooperation with Philip Rosenstiel, University of Kiel, Germany, has found a molecular explanation for the increased susceptibility to intestinal inflammation in malnutrition.  The researchers were studying an enzyme which helps to control blood pressure, kidney failure in diabetes, heart failure and lung injury, called the Angiotensin Converting Enzyme 2, or ACE2.  This enzyme was identified as the key receptor for SARS virus infections, but the researchers also discovered an entirely new function.  ACE2 controls the way our intestines take in amino acids from our food, via amino acid transporters, and in particular the uptake of the essential amino acid tryptophan.

Too little tryptophan alters our natural immune system, which changes the types of bacteria which can live in our bowels and guts, leading to higher sensitivity and eventually diarrhoea and inflamed intestines.  Increasing the intake of tryptophan in their diet provided relief for mice suffering from intestinal inflammation. The mixture of bacteria returned to normal, the inflammation died down, and the mice also became less susceptible to new attacks.

"The research shows how the food we eat can directly change the good bacteria in our intestines to bad bacteria and so influence our health”, says Thomas Perlot, the first author of the study. “Our results might also explain nutritional effects that have been known for centuries and provide a molecular link between malnutrition and the bacteria living in our intestines. This discovery could be used in the future to treat patients with a simple regulated diet or by taking tryptophan as a food supplement.  And there is hardly any risk of side effects from artificially increasing an amino acid found in the normal diet.”

Josef Penninger, the lead author, says “I have studied ACE2 for more than 10 years and was completely stunned by this novel link between ACE2 and amino acid balance in the gut. Biology continues to surprise me. Up to a billion people in the world are malnourished, especially the poor and disadvantaged. In Austria alone, around 80,000 people suffer from a chronic inflammatory bowel disease like ulcerative colitis or Crohn's disease. I hope that our findings have opened a door to a better molecular understanding how malnutrition affects human health. Whether simple tryptophan diets can indeed cure the effects of malnutrition in humans now needs to be carefully tested in clinical trials.”

See Also:Health & MedicineGastrointestinal ProblemsDietary SupplementNutritionDiet and Weight LossCholesterolDiabetesReferenceInflammation of the kidneyNeurotransmitterHeat shock proteinInflammationShare this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article

Gene that leads to severe weight gain with antipsychotic treatment discovered

ScienceDaily (May 7, 2012) — Antipsychotic medications are increasingly prescribed in the US, but they can cause serious side effects including rapid weight gain, especially in children. In the first study of its kind, researchers at Zucker Hillside Hospital and the Feinstein Institute for Medical Research identified a gene that increases weight gain in those treated with commonly-used antipsychotic drugs.

See Also:Health & MedicineDiet and Weight LossObesityPersonalized MedicineMind & BrainDieting and Weight ControlObstructive Sleep ApneaSchizophreniaReferenceDopamine hypothesis of schizophreniaDiabetes mellitus type 2PsychopharmacologyStretch marks

These findings were published in the May issue of Archives of General Psychiatry.

Second-generation antipsychotics (SGAs) were used as the treatment in this study. SGAs are commonly used to treat many psychotic and nonpsychotic disorders. However, it is important to note that these SGAs are associated with substantial weight gain, including the development of obesity and other cardiovascular risk factors. The weight gain side effect of SGAs is significant because it often results in a reduced life expectancy of up to 30 years in those who suffer from chronic and severe mental illnesses. The weight gain also prompts some to stop taking the medication, adversely impacting their quality of life.

In this genome-wide association study (GWAS), researchers first evaluated a group of pediatric patients in the US being treated for the first time with antipsychotics. They then replicated the result in three independent groups of patients who were in psychiatric hospitals in the United States and Germany or participating in European antipsychotic drug trials. The gene that was identified to increase weight gain, MC4R or melanocortin 4 receptor, has been previously identified as being linked to obesity and type 2 diabetes. In the new study, it was found that patients gained up to 20 pounds when on treatment.

"This study offers the prospect of being able to identify individuals who are at greatest risk for severe weight gain following antipsychotic treatment," said Anil Malhotra, MD, investigator at the Zucker Hillside Hospital Department of Psychiatry Research and Feinstein Institute for Medical Research. "We hope that those who are at risk could receive more intensive or alternative treatment that would reduce the potential for weight gain and we are currently conducting studies to identify such treatment."

Additional Details About the Study

Researchers conducted the first GWAS of SGA-induced weight gain in patients carefully monitored for medication adherence who were undergoing initial treatment with SGAs. To confirm results, they next assessed three independent replication cohorts: 1) a cohort of adult subjects undergoing their first treatment with a single SGA (clozapine), 2) a cohort of adult subjects treated with the same SGAs as in our discovery sample, and 3) a cohort of adult subjects in the first episode of schizophrenia and enrolled in a randomized clinical trial of antipsychotic drugs. The discovery cohort consisted of 139 pediatric patients undergoing first exposure to SGAs. The 3 additional cohorts consisted of 73, 40, and 92 subjects. Patients in the discovery cohort were treated with SGAs for 12 weeks. Additional cohorts were treated for 6 and 12 weeks.

This GWAS yielded 20 single-nucleotide polymorphisms at a single locus exceeding a statistical threshold of P10-5. This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale GWAS of obesity in the general population. Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight during the 12-week trial. These results were replicated in 3 additional cohorts, with rs489693 demonstrating consistent recessive effects; meta-analysis revealed a genome-wide significant effect. Moreover, consistent effects on related metabolic indices, including triglyceride, leptin, and insulin levels were observed.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article