Obesity Link with Enzyme 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1)

Obesity Enzyme

Weight Loss Diet Advice - Obesity Information - Body Mass Index Guide - Obesity Management
Obesity Diet - Weight Management Guide - Weight Management Program
Help For Obese Patients - Risks of Obesity

Obesity and Enzyme Link

Obesity Linked to Enzyme

The increased activity of a single enzyme in fat cells may be a common cause of obesity and obesity-linked diseases, including diabetes, according to an animal study conducted by researchers at Beth Israel Deaconess Medical Center and the University of Edinburgh and published in the Dec. 7 issue of Science. The findings could eventually pave the way for future drug development to curb visceral obesity – the “beer belly” fat concentrated in the abdomen.

“Hundreds of studies have led to the conclusion that any fat can be problematic, but it’s much, much more dangerous when it’s accumulated in the abdomen,” notes lead author Jeffrey S. Flier, M.D., an endocrinologist at Beth Israel Deaconess Medical Center and the George C. Reisman Professor of Medicine at Harvard Medical School. “Pound for pound, intra-abdominal fat is much more likely to cause diabetes, heart disease and other diseases that make up the metabolic syndrome.”

To identify the molecular mechanism behind the accumulation of the excess abdominal fat, Flier and his colleagues looked at the role of the glucocorticoid hormone cortisol, the “fight or flight” hormone that helps people survive stressful situations. Observations of patients with the endocrine disorder Cushing's syndrome – who have too much cortisol in their blood – had shown that they develop increased intra-abdominal fat as well as other metabolic symptoms. This led Flier to hypothesize that obese patients – who don't typically have increased blood cortisol levels – may be producing increased amounts of cortisol in their fat cells.

To test this hypothesis, Flier and his colleagues studied the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1), which has the unique ability to produce cortisol in cells that are not normally associated with cortisol production. This enzyme is known to be present in fat cells.

The researchers created a group of transgenic (Tg) mice that overproduce 11 beta HSD-1 in roughly the same quantities previously found in the fatty tissue of obese humans. As predicted, these mice had increased levels of cortisol in their fat, but not in their blood. The Tg mice were then compared with a group of non-Tg mice. For the first nine weeks of life both groups of mice were fed low-fat diets, and their body weights were indistinguishable. But, after nine weeks, the Tg mice steadily gained weight, and by 15 weeks of age, weighed 16 percent more than the non-Tg mice. The Tg mice were also more sensitive to weight gain when fed a high-fat diet. An external examination of the mice showed prominent weight gain in the abdominal areas of the Tg mice.

Further tests using X-ray absorptiometry to measure fat in the whole body and in the abdominal region showed that fat accumulation in the abdominal region of non-Tg mice on high-fat diets was comparable to that of Tg mice on low-fat diets. The ratio was further exaggerated when Tg mice were fed high-fat diets.

“We were surprised to find that it took only a modest increase in this enzyme to cause the mice to become viscerally obese. The animals also developed diabetes, became resistant to insulin, developed high blood lipids and actually ate more. We now also know that the mice became hypertensive,” says Flier.

“This study tells us that increasing this single enzyme in fat cells results in an unexpectedly major impact,” he adds. Coupled with findings from the University of Edinburgh showing a correlation between increased enzyme activity in fat tissue and obesity in human subjects, the findings strongly suggest that the 11 beta HSD-1 enzyme is an exciting pharmaceutical target for the treatment of visceral obesity. “Obesity is a massive problem in our population,” says Flier, who has been studying the molecular mechanisms of obesity for the past decade. “It’s linked to a huge burden of disease – hypertension, coronary disease, atherosclerosis, cancers, reproductive disorders, diabetes. In fact, an estimated 80 percent of diabetes cases would not exist in the absence of obesity. If we could attack obesity, not only would people feel better, it would also improve all of these other disease states.”

Study co-authors include Hiroaki Masuzaki, M.D. and Hiroshi Shinyama, M.D., of Beth Israel Deaconess Medical Center, and Janice Paterson, Nicholas M. Morton, M.D., John J. Mullins, M.D., and Jonathan R. Seckl, M.D., of the University of Edinburgh, Scotland. This research was funded by the National Institutes of Health (NIH) and Eli Lilly.

More About Severe Overweight

Causes of Obesity
Obesity Treatment Methods
Treatment of Morbidly Obese Patients
Obesity in Children
Abdominal Obesity Guide
Mild Obesity Guide
Morbid Obesity Guide
Malignant Obesity Guide
Super Obesity Guide

Ann OBESITY REDUCTION PROGRAM
Weight Loss Diet Program | 9 Diet Programs - Try Them All | Weight Loss Support | Weight Loss Forum
OBESITY, OVERWEIGHT and HEALTH
Weight Loss Help | Healthy Weight Advice | BMI Chart | Obesity Chart | Weight Loss For Obese Patients
Weight & Health Risks | Ideal Weight for Women | Ideal Weight for Men | Waist Circumference | Body Fat Percent
Body Fat & Health | Body Fat Calculators | Reduce Fat Belly | Obesity & Breast Cancer | What Causes Weight Gain
WEIGHT MANAGEMENT
Weight Loss Tips | Best Support Group | Forum For Obese Patients | Support Group For Obese Patients
Lose Weight After Pregnancy | Weight Loss - Pregnancy | Weight Control - Breastfeeding | Mid-Life Weight Gain
Menopause & Diet | Weight Control in Menopause | Weight and Depression | Teen Weight Loss & Healthy Eating
Help For Overweight Children | Fast Weight Loss | Raise Metabolism | Weight Loss Drugs to Reduce Obesity
Bariatric Surgery | Gastrointestinal Surgery | Health Dangers of Bariatric Surgery | Health Dangers of Gastric Bypass
Weight Loss Programs | How to Reduce Weight | Journal | Weight Loss Advice
ENERGY NEEDS
Calories Index | Guide to Calorie Needs | Calorie Needs for Women | Calorie Needs Men | Calories & Weight Loss

© 2000-2007 Ann. All rights reserved.