Making 'good' fat from muscle and vice versa

August 21, 2008

Molecular switch found in mice could lead to future obesity treatments, scientists say

BOSTON--A surprise discovery -- that calorie-burning brown fat can be produced experimentally from muscle precursor cells in mice -- raises the prospect of new ways to fight obesity and overweight, say scientists from Dana-Farber Cancer Institute.

Reporting in the Aug. 21 issue of the journal Nature, the researchers demonstrated that brown fat, which is known as the "good" form of fat -- so called because it burns calories and releases energy, unlike "bad" white fat that simply stores extra calories -- can be generated from unspecialized precursors that routinely spawn skeletal muscle.

The team led by Dana-Farber's Bruce Spiegelman, PhD, showed that a previously known molecular switch, PRDM16, regulates the creation of brown fat from immature muscle cells. They also determined that the process is a two-way street: Knocking out PRDM16 in brown fat cells can convert them into muscle cells. However, Spiegelman called the latter an "experimental lab trick" for which he currently envisions no practical applications.

The "huge surprise" of the study results, he said, was that muscle precursor cells known as "satellite cells" are able to give birth to brown fat cells under the control of PRDM16.

Spiegelman said the finding confirms that PRDM16 is the "master regulator" of brown fat development. The confirmation will spur ongoing research in his laboratory, he said, to see if drugs that rev up PRDM16 in mice -- and potentially, in people -- could convert white fat into brown fat and thereby treat obesity. Another strategy, he said, might be to transplant brown fat cells into an overweight person to turn on the calorie-burning process.

"I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity," said Spiegelman, the senior author of the paper. The lead author is Patrick Seale, PhD, a postdoctoral fellow in the Spiegelman lab.

Another paper in the same issue of Nature described a different trigger of brown fat production, a molecule called BMP7. A commentary in the journal by Barbara Cannon, an internationally recognized researcher in the biology of fat cells at the University of Stockholm, said that the two reports "take us a step closer to the ultimate goal of promoting the brown fat lineage as a potential way of counteracting obesity."

The Spiegelman group has long studied fat cells both as a model for normal and abnormal cell development, which relates to cancer, and also because fat cells play such a key role in the growing epidemics of obesity and diabetes.

There is much interest in brown fat's role in regulating metabolism. Rodents and human infants have abundant brown fat that dissipates food energy as heat to protect against the cold. Though human adults have little brown fat, it apparently does have a metabolic function, including the potential to be amplified in some way to combat obesity.

In 2007, Spiegelman and colleagues reported they had inserted PRDM16 genes into white fat precursors, which they implanted under the skin of mice. The PRDM16 switch coaxed the white fat precursors to produce brown fat cells instead of white. To Spiegelman, this suggested the possibility of transplanting PRDM16-equipped white fat precursors into people who are at high risk of becoming obese, to shift their metabolism slightly into a calorie-burning mode.

The new research adds another potential source of brown fat -- the muscle cell progenitors, or myoblasts, that exist in the body to replace mature muscle cells as needed. The progenitors, which can be thought of as "adult stem cells," are committed to becoming specialized muscle cells when activated by appropriate signals, or, as the study revealed, brown fat cells when PDRM16 is turned on. The PRDM16 trigger "is very powerful at what it does," said Spiegelman, who is also a professor of cell biology at Harvard Medical School.

Dana-Farber Cancer Institute

---

---

	Outsmarting the Midlife Fat Cell: Winning Weight Control Strategies for Women Over 35 to Stay Fit Through Menopause by M.P.H.,R, Debra Waterhouse (Author) Menopausal weight gain is "the most stubborn weight gain you'll ever experience," says Debra Waterhouse in Outsmarting the Midlife Fat Cell. This book follows her bestselling Outsmarting the Female Fat Cell, customizing the program for women ages 35 to 55. The book is easy to read, makes difficult concepts simple to understand, and has helpful checklists to keep you on track. Outsmarting the Midlife Fat Cell explains the role of fat cells before and during menopause and why midlife weight gain is such a pervasive problem. A woman's 30 billion fat cells get bigger and "more stubborn" during midlife, explains Waterhouse, because when they detect a lowered estrogen level, they step in to produce more estrogen and get larger as they get more active. Dieting doesn't work; instead of slimming...
	OUTSMARTING THE FEMALE FAT CELL: THE FIRST WEIGHT-CONTROL PROGRAM DESIGNED SPECIFICALLY FOR WOMEN by Debra Waterhouse (Author) The first diet and nutrition book designed specifically for women introduces an effective weight-loss program for women of all ages and is designed to permanently "deactivate" the female fat cell. Lit Guild. Tour.
	Outsmarting the Female Fat Cell--After Pregnancy: Every Woman's Guide to Shaping Up, Slimming Down, and Staying Sane After the Baby by Debra Waterhouse (Author) very woman who's had a baby knows how difficult it is to take off the extra weight, despite those unrealistic articles promising that you'll be back into your pre-pregnancy clothes within six weeks. Postpartum dieting can actually add weight and slow down the metabolism, making it virtually impossible to shed those stubborn pounds. Outsmarting the Female Fat Cell-After Pregnancy shows women why it's so difficult to lose the weight quickly, and why, if women don't adopt a sensible eating and exercise plan (as opposed to crash dieting), they will probably never take off the extra pounds. Whether you had a baby five days ago, or five years ago, bestselling author Debra Waterhouse shows women how to shed those hard-to-budge post-partum pounds, sensibly and healthfully.
	How I Gave Up My Low-Fat Diet and Lost 40 Pounds (Revised and Expanded Edition) by Dana Carpender (Author) This is a breezy, chatty, non-technical, fun-to-read explanation of low carbohydrate dieting -- why it works, the surprising health benefits, and most importantly, how to "do" the diet. Or, rather, diets,since the book details three very different main approaches to controlling carbohydrates (including the Basic Low Carb Diet, similar to Atkins or Protein Power, and the Mini-Binge Diet, popularized as The Carbohydrate Addict's Diet), plus several variations, finally summing up the basic principles which tie them all together. The point is to give the reader the tools necessary to construct a new way of eating that will fit his or her body, psyche, and lifestyle, thus allowing them to stay slim, energetic, and healthy for life.
	The Brown Fat Revolution: Trigger Your Body's Good Fat to Lose Weight and Be Healthier by James Lyons (Author) In today’s youth-obsessed culture, mixed messages about diet, exercise, and skin care are everywhere. But one thing is clear: fat is always the enemy. Right? Wrong, says James R. Lyons, M.D. In BROWN FAT REVOLUTION, Dr. Lyons explains that, contrary to popular belief, fat is the key to a youthful looking face and body. But it has to be the right kind of fat. Unlike the yellow, mushy, unhealthy fat that makes us look old, brown fat is healthy, firm, and resilient and gives our bodies a youthful appearance. In Dr. Lyons’s nearly 30 years of clinical experience, he'd noticed a brown fat in lean patients. His findings pointed to the presence of different types of fat in the body and suggested that the quality of the fat is determined by external factors. These observations are...
	Tapping the potential of fat cells.(Indiana Center for Vascular Biology and Medicine): An article from: Medical Update by Mary Hardin (Author) This digital document is an article from Medical Update, published by Benjamin Franklin Literary & Medical Society, Inc. on March 1, 2004. The length of the article is 736 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Tapping the potential of fat cells.(Indiana Center for Vascular Biology and Medicine) Author: Mary Hardin Publication: Medical Update (Newsletter) Date: March 1, 2004 Publisher: Benjamin Franklin Literary & Medical Society, Inc. Volume: 29 Issue: 9 Page: 6(1) Distributed by Thomson...
	Fat Burning Foods: An A-Z list of Foods that Burn Fat to Start a Healthy Diet by C Elias (Author) Reviews (see below) say "straight to the point..." "convenient..." "very tasty..." "Great book for the price" "...explains about which foods can help you lose weight, why, and also everything else that they can do for your body..." "...clear no - nonsense..." Discover the best fat burning foods - this is a nutrition list of over 80 foods that can burn fat will help you lose weight naturally. This is by far the most comprehensive list you will find anywhere - and it is in a handy book size in alphabetical order, listing why each food will help you burn fat. You will find no fluff or long pages of explanations. This is a hard-hitting, straight to the point book on what foods are now known to be healthy fat burning foods and why. When you next go shopping - don't leave home without it!
	Fat Wars: 45 Days to Transform Your Body by Brad J. King (Author) Yes, it's you against your 30 billion fat cells! They stay with you forever and can expand to store as much fat asyou choose to stash in them. Fat Wars: 45 Days to Transform Your Body isn't another diet book. Instead, it's the book that will tell you how your body works: how it makes energy, how it stores fuel (fat), how it moves fat around and how to get it to burn that fat instead of putting it into storage. Then Fat Wars will tell you how to take that knowledge to craft an eating and activity plan that will work for you. Instead of engaging in endless losing battles with your wily fat cells, find out what makes them tick. Then plan to live in harmony with your body and look forward to a leaner, fitter, and healthier you in 45 days!
	OUTSMARTING THE FEMALE FAT CELL by Debra Waterhouse (Author)
	Outsmarting the Midlife Fat Cell by Debra Waterhouse (Author)