BUSM Study Reveals B cells as Therapeutic Targets to Alter Obesity-Associated Inflammation and Type 2 Diabetes
FOR IMMEDIATE RELEASE, March 12, 2013,
Jenny Eriksen Leary, 617-638-6841, firstname.lastname@example.org
(Boston) – New research from Boston University School of Medicine (BUSM) reveals that B cells regulate obesity-associated inflammation and type 2 diabetes through two specific mechanisms. The study, published in the Proceedings of the National Academy of Sciences, indicates the importance of continuing to explore B cells as a therapeutic target to treat these diseases. Barbara Nikolajczyk, PhD, associate professor of microbiology at BUSM, is the study’s senior author.
The incidence of diabetes continues to rise at alarming rates. According to the National Institute of Diabetes and Digestive and Kidney Diseases, the disease now affects approximately 25.8 million Americans. In 2007, the National Institutes of Health estimated that the direct and indirect costs of diabetes were a staggering $174 billion.
Type 2 diabetes, which is a common result of obesity, occurs when the body produces insulin but cannot use it properly (insulin resistance) or the body does not produce enough insulin. The body needs insulin to absorb glucose and generate energy. If the body does not produce and respond to insulin appropriately, it can, over time, lead to various complications such as cardiovascular disease, nerve damage, kidney disease and blindness.
Previous research has shown that B cells, which are white blood cells of the immune system, promote inflammation and can lead to the development of type 2 diabetes, but the mechanisms underlying B cell function were unclear.
The results of this study shed light on that question and indicate that B cells secrete a pro-inflammatory ratio of proteins called cytokines, which directly promote the insulin resistance that characterizes type 2 diabetes. The researchers also demonstrated that B cells directly regulate inflammatory T cells, an immune cell type known to cause insulin resistance in animal models of disease.
“Now that we have identified the specific mechanisms by which B cells promote inflammation, we can help develop novel, targeted approaches to treat type 2 diabetes,” said Nikolajczyk. “Our study supports the continued exploration of FDA-approved B cell depletion drugs, which are known to be generally safe and effective, as novel agents to prevent obesity-associated inflammation and type 2 diabetes.”
Research included in this study was supported in part by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under grant award numbers R21DK089270 and R56DK096525 (PI: Nikolajczyk) and R56DK090455 (PI: Gerald Denis); the NIDDK’s Boston Area Diabetes Endocrinology Research Center Pilot Program and the Boston Nutrition Obesity Research Center under grant award number DK046200; the NIH’s National Institute of Dental and Craniofacial Research under grant award number 5R21DE021154 (PI: Nikolajczyk); the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Immunology Training Program under grant award number AI007309; the NIH’s National Heart, Lung, and Blood Institute’s Hematology Training Program under grant award number HL007501; and the Evans Center for Interdisciplinary Biomedical Research at BUSM (PI: Nikolajczyk and Denis).
BUSM study identifies Adenosine Receptor’s role in regulating high fat diet-induced obesity and Type 2 Diabetes
Contact: Jenny Eriksen Leary, 617-638-6841, email@example.com
(Boston) – A recent study led by Boston University School of Medicine (BUSM) demonstrates that the A2b-type adenosine receptor, A2bAR, plays a significant role in the regulation of high fat, high cholesterol diet-induced symptoms of type 2 diabetes. The findings, which are published online in PLoS ONE, also identify A2bAR as a potential target for the treatment of type 2 diabetes.
Katya Ravid, DSc/PhD, professor of medicine and biochemistry and director of the Evans Center for Interdisciplinary Biomedical Research at BUSM, led this study. Colleagues from Ravid’s lab who collaborated on this research include Hillary Johnston-Cox, BSc (MD/PhD, 2014) and Milka Koupenova-Zamor, PhD. Noyan Gokce, MD, associate professor of medicine at BUSM, and Melissa Farb, PhD, a postdoctoral fellow at BUSM, also collaborated on the study.
Diets that are high in fat and cholesterol induce changes in how the body regulates blood glucose levels. Exercise induces an increased production adenosine, a metabolite produced naturally by cells. A2bAR, a naturally occurring protein receptor found in the cell membrane, is activated by adenosine. This receptor is known to play an important role in regulating inflammation, which is associated with type 2 diabetes and obesity.
To examine the association of A2bAR activation with a diet high in fat and cholesterol, the researchers used an experimental model that lacked A2bAR and compared the results with a control group. When the experimental model group was given a diet high in fat and cholesterol, there was an increase in the development of obesity and signs of type 2 diabetes. The signs demonstrated in the study included elevated blood glucose levels and increased in insulin levels. When the control group was given the same diet, however, the levels of A2bAR increased, resulting in decreased insulin and glucose levels and obesity.
A novel link also was identified between the expression of A2bAR, insulin receptor substrate 2 (IRS-2) and insulin signaling. The results showed that the level of IRS-2, a protein that has previously been shown to mediate the effect of insulin, was impaired in tissues of the experimental model lacking A2bAR, causing higher concentrations of blood glucose. When A2bAR was activated in the control group using a pharmacologic agent with a diet high in fat and cholesterol, the level of IRS-2 was upregulated, lowering blood glucose.
“The pharmacologic activation of A2bAR demonstrated its newly identified role in signaling down to regulate the levels of IRS-2, which then improved the signs of high fat diet-induced type 2 diabetes,” said Ravid.
The prevalence of type 2 diabetes and obesity continues to increase in developed countries and both factors are known to contribute to the development of cardiovascular disease. According to the World Health Organization, 346 million people worldwide have diabetes and 90 percent of those people have type 2 diabetes.
To correlate these results in humans, the researchers then examined fat tissue samples from obese individuals. The results showed that A2bAR expression is high in fat from obese individuals, marked by inflammation, compared to lean ones, and is strongly correlated with IRS-2 expression.
“Our study suggests the important role of A2bAR in maintaining the level of IRS-2, a regulator of glucose and insulin homeostasis,” added Ravid.
This study was funded in part by the National Heart, Lung and Blood Institute under award numbers HL93149 (Katya Ravid) and HL084213 (Noyan Gokce). Click on the following link to view the study online: http://dx.plos.org/10.1371/journal.pone.0040584.
Study Finds Socioeconomic Status Linked to Weight Gain and Risk of Obesity in African American Women
Contact: Gina DiGravio, 617-638-8480, firstname.lastname@example.org
(Boston) – Socioeconomic status across one’s lifetime is related to weight gain and risk of obesity in African American women, according to a new study led by researchers from the Slone Epidemiology Center at Boston University. These findings currently appear online in the journal Ethnicity & Disease.
The researchers followed 23,601 African American women under the age of 55 from 1995 to 2009. These women were participants in the Black Women’s Health Study, a follow-up study of the health of African Americans conducted by the Slone Epidemiology Center. The women provided information on their education, the education of their parents and updated information on their own weight over the follow-up period.
The researchers found that women whose parents had not completed high school gained more weight and more often became obese in adulthood than women who had a parent with a college degree. “However, if the woman herself had completed college, she was not at higher risk of obesity regardless of her parents’ educational level,” explained lead author Patricia Coogan, DSc, senior epidemiologist at the Slone Epidemiology Center and associate professor of epidemiology at the Boston University School of Public Health.
According to the researchers, low levels of parental and current education were associated with greater weight gain and higher obesity risk. However, over a lifetime, women at the highest level of current education (college graduate) had the lowest weight gain and risk of obesity regardless of their parents’ educational achievement. Current educational level of “some college” did not provide the same protective effect on weight gain and obesity risk.
“Our results suggest that women who were disadvantaged in childhood, as indicated by low level of parental education, have greater weight gain as adults, but this tendency can be largely overcome if the woman herself has a high level of education,” said Coogan. “A high level of education may be a marker of more access to healthy food and other factors that influence weight gain,” she added.
Funding for this study was provided by the National Cancer Institute.
Americans at LARGE
Centers for Disease Control (CDC) recently took the vital signs of Americans and declared that more needs to be done to combat obesity. Currently, 68% of Americans are either overweight or obese. Excess body fat increases your risk of heart disease, certain cancers, stroke, and diabetes — all major killers of Americans.
Correctly, the CDC has identified that there isn’t a single, simple solution to this problem, but rather, it has to be a team effort of the states, communities, and personal changes to trim down America. States can bring more local, waist-friendly fruits and vegetables to schools and the workplace. Communities can support and maintain safe outdoor spaces such as playgrounds and bike paths to encourage physical activity. On a personal level, the time has come for all of us to consider a diet and lifestyle makeover.
Taking gradual and realistic steps to change your diet and lifestyle is less overwhelming and more likely to be successful. To help you, try these 52 Small Steps to Losing Weight. Changes can be made……one small step at a time.
Medical spending for an obese person averages $1,400 more a year than an individual of normal weight – a health-related expenditure that has doubled from nearly a decade ago and includes treating diabetes, heart disease and other ailments found in those overweight, according to a recent study. Caroline Apovian, MD, Boston Medical Center Director of Clinical Research at the Obesity Research Center, can discuss ways of changing behavior and health outcomes to reduce obesity.
Contact Caroline Apovian, 617-414-1816, email@example.com
Obese children hospitalized for such related conditions as asthma, diabetes, gallbladder disease, pneumonia and mental disorders soared dramatically, both in patient numbers and total costs. The published study prompted Caroline Apovian, MD, Boston Medical Center director of the Obesity Research Center, to call for a national health plan effort “to stave off a curtailed healthy future for our kids.”
In the nation’s annual obesity rankings, 23 states reported higher adult obesity rates over the past year with concerns about Medicare’s higher costs to treat fat baby boomers. Colorado had the lowest rate of obese adults followed by Massachusetts and Connecticut. Caroline Apovian,MD, Director of Nutrition and Weight Management at Boston Medical Center, can discuss the issues and what to do about them.
Contact Caroline Apovian, 617-414-1816, firstname.lastname@example.org
Caroline Apovian, M.D., BU School of Medicine associate professor of medicine and pediatrics, can discuss how tough economic times are having an impact on children as struggling parents turn to cheap fast food to feed their families.
Contact Dr. Caroline Apovian, 617-414-1816, email@example.com