Gut Microbe Changes That Usually Promote Obesity And Diabetes Are Beneficial During Pregnancy

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Main Category: Pregnancy / Obstetrics
Also Included In: GastroIntestinal / Gastroenterology;  Diabetes
Article Date: 05 Aug 2012 - 0:00 PDT Current ratings for:
Gut Microbe Changes That Usually Promote Obesity And Diabetes Are Beneficial During Pregnancy

The composition of microbes in the gut changes dramatically during pregnancy, according to a study published by Cell Press in the August 3rd issue of the journal Cell. Although these changes are associated with metabolic disease under most circumstances, they could be beneficial in pregnant women.

"This is the first in-depth characterization of the gut microbiota associated with pregnancy," says senior study author Ruth Ley of Cornell University. "The findings suggest that our bodies have coevolved with the microbiota and may actually be using them as a tool - to help alter the mother's metabolism to support the growth of the fetus."

In nonpregnant animals, changes to gut microbe composition can cause symptoms of metabolic syndrome, including weight gain, abnormal glucose metabolism, and inflammation - an immune response that normally protects the body but can cause health problems. These symptoms also appear during pregnancy, but the underlying causes have been unclear, and few studies have examined the potential link to gut microbiota during pregnancy.

To address this question, Ley and her team obtained stool samples from 91 pregnant women. They found that gut microbes changed in composition from the first trimester to the third trimester, becoming less "normal" and less diverse over time. Health-boosting bacteria decreased in abundance, while disease-related bacteria increased in number. In addition, signs of inflammation increased over the course of the pregnancy. "The changes in gut microbes were not related to diet, so we think the immune system or hormones play a role," Ley says.

When gut microbes from pregnant women were transferred to healthy germ-free mice, animals that received microbes from the third trimester became fatter and had higher levels of inflammation markers and worse glucose metabolism than mice that received microbes from the first trimester.

"By the third trimester, the microbiota can induce changes in metabolism," Ley says. "In the context of pregnancy, these metabolic changes in the mother are healthy, because they promote energy storage in fat tissue and help support the fetus. Outside of pregnancy, however, these changes can lead to the development of type 2 diabetes and other health problems."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pregnancy / obstetrics section for the latest news on this subject. Koren et al.: "Remodeling of the gut microbiome and metabolic changes during pregnancy."
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Hope For New Obesity And Diabetes Treatments From Mechanism That Turns White Fat Into Energy-Burning Brown Fat

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Main Category: Obesity / Weight Loss / Fitness
Also Included In: Diabetes
Article Date: 05 Aug 2012 - 0:00 PDT Current ratings for:
Hope For New Obesity And Diabetes Treatments From Mechanism That Turns White Fat Into Energy-Burning Brown Fat

Columbia University Medical Center (CUMC) researchers have identified a mechanism that can give energy-storing white fat some of the beneficial characteristics of energy-burning brown fat. The findings, based on studies of mice and of human fat tissue, could lead to new strategies for treating obesity and type 2 diabetes. The study was published in the online edition of the journal Cell.

Humans have two types of fat tissue: white fat, which stores excess energy in the form of triglycerides, and brown fat, which is highly efficient at dissipating stored energy as heat. Newborns have a relative abundance of brown fat, as protection against exposure to cold temperatures. In adults, however, almost all excess energy is stored as white fat.

"Turning white fat into brown fat is an appealing therapeutic approach to staunching the obesity epidemic, but it has been difficult to do so in a safe and effective way," said study leader Domenico Accili, MD, professor of Medicine and the Russell Berrie Foundation Professor at CUMC.

White fat can be "browned" with a class of drugs called thiazolidazines (TZDs), which increase the body's sensitivity to insulin. However, TZDs have many adverse effects - including liver toxicity, bone loss, and, ironically, weight gain - which have limited the use of these drugs.

The current study was undertaken to learn more about the function of TZDs, with the ultimate goal of developing better ways to promote the browning of white fat.

Scientists have known that TZDs promote the browning of white fat by activating a cell receptor called peroxisome proliferator-activated receptor-gamma (ppar-gamma), but the exact mechanism was not clear. To learn more, Dr. Accili and his colleagues studied a group of enzymes called sirtuins, which are thought to affect various biological processes, including metabolism.

The researchers had previously shown in mice that when sirtuin activity increases, so does metabolic activity. In the present study, they found that sirtuins boost metabolism by promoting the browning of white fat. "When we sought to identify how sirtuins promote browning, we observed many similarities between the effect of sirtuins and that of TZDs," said lead author Li Qiang, PhD, associate research scientist in Medicine at CUMC.

Sirtuins work by severing the chemical bonds between acetyl groups and proteins, a process known as deacetylation. "So the next question was whether sirtuins remove acetyl groups from ppar-gamma and, indeed, that was what we found," said Dr. Qiang.

To confirm that the deacetylation of ppar-gamma is crucial to the browning of fat, the researchers created a mutant version of ppar-gamma, in effect mimicking the actions of sirtuins. The mutation promoted the development of brown fat - like qualities in white fat.

"Our findings have two important implications," said Dr. Accili. "First, they suggest that TZDs may not be so bad - if you can find a way to tweak their activity. Second, one way to tweak their activity is by using sirtuin agonists - that is, drugs that promote sirtuin activity."

"The truth is, making sirtuin agonists has proved to be a real bear - more promise than fact," he continued. "But now, for the first time, we have a biomarker for good sirtuin activity: the deacetylation of ppar-gamma. In other words, any substance that deacetylates ppar-gamma should in turn promote the browning of white fat and have a beneficial metabolic effect."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our obesity / weight loss / fitness section for the latest news on this subject. Dr. Accili's paper is titled, "Brown Remodeling of White Adipose Tissue by SirT1-Dependent Deacetylation of Ppar-gamma." The other contributors are Ning Kon (CUMC), Wenhui Zhao (CUMC), Sangkyu Lee (University of Chicago, Chicago, Illinois), Yiying Zhang (CUMC), Michael Rosenbaum (CUMC), Yingming Zhao (University of Chicago), Wei Gu (CUMC), and Stephen R. Farmer (Boston University School of Medicine, Boston, Mass.)
This research was supported by grants from the National Institutes of Health (HL087123, DK58282, DK64773, DK063608, and RR024156).
The authors declare no financial or other conflicts of interest.
Columbia University Medical Center Please use one of the following formats to cite this article in your essay, paper or report:

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Clues To Development Of The Pancreas Provided By Rare Genetic Disorder Could Lead To Diabetes Therapy

Main Category: Diabetes
Also Included In: Genetics
Article Date: 13 Dec 2011 - 0:00 PST

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A rare genetic disorder has given researchers at the University of Exeter a surprising insight into how the pancreas develops. The finding provides a clue to how it may be possible to 'programme' stem cells - master cells in the body that can develop into specialised cells - to become pancreatic cells.

Pancreatic agenesis is a rare condition in which the body is unable to produce a pancreas. The pancreas plays an essential role in regulating levels of sugar (glucose) in the blood. It does this by the release of the hormone insulin, which is generated and released by cells known as pancreatic beta cells. It also produces enzymes to help digest and absorb food.

Rare mutations in the genes PDX1 and PTF1A have previously been shown to cause pancreatic agenesis, but have only been identified in a handful of families affected by the condition. Until now, the underlying causes of most cases have been unknown.

In a paper published in Nature Genetics, an international team of researchers led by scientists from the Peninsula College of Medicine and Dentistry at the University of Exeter report a mutation in the gene GATA6 found in fifteen out of twenty-seven individuals with pancreatic agenesis. The study, funded by organisations including the Wellcome Trust, Diabetes UK and the National Institute for Health Research, establishes a key role for GATA6 in the development of pancreatic cells.

The finding was particularly surprising as switching off the GATA6 gene in mouse models appeared to make no difference to the development of the pancreas.

Professor Andrew Hattersley from the Peninsula College of Medicine and Dentistry, said: "This rare genetic condition has provided us with a surprising insight into how the pancreas develops. What is it that programmes cells to become pancreatic beta cells? Our study suggests that GATA6 plays a very important role in this process and we hope this will help the crucial work to try and make beta-cells for patients with type 1 diabetes."

Whilst pancreatic agenesis is an extreme form of pancreatic dysfunction, far more common is diabetes. In type 1 diabetes, which generally develops in childhood, the immune system attacks and destroys pancreatic beta cells and the body is unable to regulate glucose levels, whilst in type 2 diabetes, the beta cells gradually decline until, usually during adulthood, they cease to function.

Professor Sian Ellard, also from Peninsula College of Medicine and Dentistry, added: "This discovery was possible because new sequencing approaches meant we could test all the genetic information in one go and because with the help of doctors throughout the world we were able to study 27 patients with a very rare condition."

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Obesity And Diabetes Undermining America's Overall Health

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Main Category: Public Health
Also Included In: Obesity / Weight Loss / Fitness;  Diabetes
Article Date: 08 Dec 2011 - 6:00 PST

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America's overall health is being undermined by obesity and diabetes, other chronic diseases, and child poverty; these detriments have been deemed greater than the benefits from improvements in cardiovascular deaths, preventable hospitalizations and smoking cessation, says a new report titled 2011 America's Health Rankings.

The Rankings is a collaboration between United Health Foundation, the America Public Health Association, and Partnership for Prevention.

No improvement in overall health - while the country's overall health improved by an average of 0.5% from 2000 to 2010 and 1.6% since the 1990s, the rate was unchanged from 2010 to 2011, the authors wrote.

Vermont is still the healthiest state in the USA, and has been so for the last five years. New York and New Jersey moved up six places and are the most improved states - mainly due to the impressive numbers of people who gave up smoking. Idaho has slipped from ninth to nineteenth place, while Alaska went down five places.

Below are the five healthiest and five unhealthiest states, according to the report:

United Health Foundation board member and executive vice president and chief of medical affairs, UnitedHealth Group, Reed Tuckson, M.D., said:

"Where people live matters. Every state can make improvements to ensure healthier quality of lives for their residents. In the history of the Rankings, we have seen many examples of stakeholders coming together to improve their standing.

States such as Tennessee and Maine - which made explicit efforts to improve their rankings - have shown us that improved public health is achievable but must be tackled in a concerted and aggressive way."

Jud Richland, M.P.H., president and CEO of Partnership for Prevention, said:

"The Rankings provides comprehensive data states can use to develop prevention solutions and health-improvement plans - empowering their residents to live long, healthy and productive lives."

The authors explain that their latest Rankings give a snapshot of each state, and is based on 23 measures that include several promising trends: Smoking - there are 25.4% fewer smokers in the USA today than in 2001. In 2011, 17.3% of US adults smoked, compared to 17.9% a year before.Preventable hospitalizations - there were 68.2 preventable hospitalizations per 1,000 Medicare beneficiaries in 2011, compared to 70.6 a year before - 17.3% less than in 2001.Cardiovascular deaths - in 2011, there were 270.4 cardiovascular deaths per 100,000 people, compared to 278.2 a year before - a 22.2% drop since 2001.The following undesirable trends more than offset improvements: Childhood poverty - 21.5% of US children lived in poverty in 2011, compared to 20.7% a year before - 33.5% more than in 2001.Diabetes - 8.7% of US adults were diagnosed with diabetes in 2011, compared to 8.3% a year before - 42.6% higher than in 2001.Obesity - the national adult obesity rate reached 27.5% in 2011, compared to 26.9% a year before - up 37.5% compared to 2001. This year is the first in which not one US state has an obesity rate below 20%.The authors remarked on how good and bad trends erased each other out - for every person who gave up smoking in 2011, another became obese.

Dr. Tuckson said:

"While this year's Rankings shows some important improvements, we also see some very alarming trends - particularly diabetes and obesity - that, left unchecked, will put further strain on our country's already strained health care resources.

At a time when the nation, states and individual families are grappling with tightening budgets and growing health care expenses, this year's Rankings sends a loud wakeup call that the burden of preventable chronic disease will continue to get worse unless we take urgent action.

Broad collaboration is the only path to health and financial progress. Government, the private sector, philanthropy and community-based organizations all need to join in a data-driven process to determine and address priorities."

Georges C. Benjamin, M.D., executive director of the American Public Health Association, said:

"Addressing the leading causes of these largely preventable diseases is essential if we are going to improve the nation's health. America's Health Rankings gives us a tool to gauge where we are and where we need to go, and the numbers should drive us to action."

Even though smoking prevalence has dropped from 29.5% in 1990 to 17.3% this year, it is still the cause of 1 in every 5 premature deaths per year (443,000). In 1990, only 11.6% of US adults were obese, compared to 27.5% this year, an increase of 137%. More than 1 in every 4 adults are obese today; approximately 65 million people. Obesity prevalence continues to increase and is costing the nation $147 billion just in direct health care expenditure. Experts say the main reason for the obesity explosion is bad eating habits and lack of physical activity. There are over 20 million adults in the USA today who have been diagnosed with diabetes, i.e. 8.7% of all adults. In 1996, the figure was 4.4%. Studies have indicated that within the next four decades between 1 in every 3 to 5 adults will have been diagnosed with diabetes. The authors say this means there are millions of people today who are either at risk of developing diabetes, or already have it but do not know (have not yet been diagnosed).

By the end of this decade, about 10% of all health care spending will be channeled towards treating diabetes and prediabetes - an annual total of nearly $500 billion (compared to $208 billion today).

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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