Metabolic Defect In Liver That Can Lead To Obesity Found By Monell Researchers
Main Category: Obesity / Weight Loss / Fitness News
Article Date: 28 Jul 2007 - 7:00 PDT

Researchers at the Monell Chemical Senses Center have identified a genetically-transmitted metabolic defect that can lead to obesity in some individuals. The defect involves decreased production of liver enzymes needed to burn fat and may help to explain why some people become obese while others remain thin.

The global obesity epidemic is thought to be caused in part by the increased availability and intake of high calorie foods rich in fat and carbohydrates. These foods promote weight gain in humans and other animals, leading to a diet-induced obesity. The propensity to gain weight and become obese when consuming a high-fat diet is at least partially controlled by genes.

"Results of this study help explain the interaction between genes and diet that underlies diet-induced obesity," comments senior author Mark Friedman. "They also point to a way to identify individuals at risk for dietary obesity, perhaps even during childhood before the development of unhealthy eating habits."

The current study, published in the August issue of Metabolism, demonstrates that genetic susceptibility to diet-induced obesity is due to a reduced capacity to burn fat.

Fat is one of the fuels that the body's cells burn to provide energy. This process, known as fat oxidation, takes place inside mitochondria, the cell's power plants for generating energy.

If the ability to oxidize fat is impaired, the body's capacity to make energy is reduced. This leads to increased hunger and overeating, as the body tries to increase the amount of energy available to meet its needs.

When the diet is low in fat, a reduced ability to burn fat has relatively little impact on energy production. However, if fat oxidation is impaired and the diet is high in fat, a greater proportion of calories cannot be used and food intake increases to cover the energy deficit. Because fat fuels are stored in fat tissue when they're not oxidized, the increased food intake causes weight gain.

To determine whether preexisting differences in fat oxidation might contribute to individual susceptibility to diet-induced obesity, Friedman and lead author Hong Ji used rats that differ in their genetic predisposition to gain weight and become obese when fed a high-fat diet.

The closely-related strains weigh the same and eat the same amount of calories when fed a low-fat diet. However, when switched to a high-fat diet, the strain that is obesity-prone overeats and becomes obese, while the obesity-resistant strain does not.

The researchers found that even when eating a low-fat diet and still lean, the obesity-prone rats were less able to burn fat than were the obesity-resistant rats. This intrinsic deficit in fat oxidation was associated with a decrease in the capacity to make two liver enzymes. One, CD36, is responsible for transferring fat fuels into liver cells, while the second enzyme, acyl-coenzyme A dehydrogenase, begins the oxidation process in mitochondria.

When fed a high-fat diet, the obesity-prone rats overate and became obese, gaining 36% more weight than resistant animals. Fat oxidation was further compromised due to a decreased ability to make CPT1A, the liver enzyme responsible for transporting fat into mitochondria.

"The inherited propensity to gain weight when eating a high-fat diet appears to be due to a preexisting limit on the ability to burn fat in the liver. This defect persists during the development of obesity and is then further compounded by additional deficits in the fat oxidizing machinery," comments Friedman.

Other studies in Friedman's laboratory have demonstrated that a decrease in fat oxidation and energy production in the liver generates a signal that stimulates eating. Experiments in his and other laboratories have also found that treatments that increase fat oxidation reduce food intake and cause weight loss in obese rodents.

With this in mind, Friedman notes, "The present findings point to fat oxidation in the liver as a target for the development of drugs that suppress appetite and promote weight loss in obese individuals."

Future studies will guide development of such interventions by examining more closely the function and activity of the target enzymes.

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Article adapted by Medical News Today from original press release.
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The Monell Chemical Senses Center is a nonprofit basic research institute based in Philadelphia, Pennsylvania. For 39 years, Monell has been the nation's leading research center focused on understanding the senses of smell, taste and chemical irritation: how they function and affect lives from before birth through old age. Using a multidisciplinary approach, scientists collaborate in the areas of: sensation and perception, neuroscience and molecular biology, environmental and occupational health, nutrition and appetite, health and well being, and chemical ecology and communication.

For more information about Monell, please visit http://www.monell.org.

CITATION: Ji, H. and Friedman, M.I. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity. Metabolism, 2007, 56, 1124-30.

Source: Leslie Stein
Monell Chemical Senses Center

http://www.medicalnewstoday.com/articles/77845.php

http://www.forbes.com/forbeslife/he...cout606747.html

Weight Gain May Be Rooted in Liver Enzyme Defect
08.03.07, 12:00 AM ET

FRIDAY, Aug. 3 (HealthDay News) --A genetic defect in the liver explains why some people become obese while others remain thin, a new study suggests.

The defect may prevent some people's liver enzymes from burning fat effectively and may actually cause people to eat more in an effort to create enough energy for their bodies, according to researchers at the Monell Chemical Senses Center, in Philadelphia. The finding could lead to a genetic test that would identify people at risk of becoming overweight.

"Results of this study help explain the interaction between genes and diet that underlies diet-induced obesity," senior author Mark Friedman said in a prepared statement. "They also point to a way to identify individuals at risk for dietary obesity, perhaps even during childhood before the development of unhealthy eating habits," he said.

Cells burn fat to provide energy for the body. This process, known as fat oxidation, takes place inside mitochondria, the cells' power plants for generating energy. If the ability to oxidize fat is impaired, the body's capacity to make energy is reduced. This leads to increased hunger and overeating, as the body tries to increase the amount of energy available to meet its needs.

Paradoxically, this means people and animals with the genetic inclination to become obese will actually consume more food despite their weight gain. The effect is not noticeable when people and animals are on a low-fat diet -- it is the presence of excess fat in the diet that triggers the problems with oxidation and fat storage, the researchers said.

Friedman's team compared weight gain in rats that were genetically inclined toward obesity with rats that were not. When both groups were fed low-fat diets, the rats all weighed the same, although the obesity-prone rats struggled to burn the same amount of fat. But, when the researchers switched the rats to a high-fat diet, the rats that were genetically inclined toward obesity ate more and gained 36 percent more weight than the slender rats.

The reduction in fat burning capacity is tied to a lack of two liver enzymes -- CD36 and acyl-coenzyme A dehydrogenase, the researchers said. CD36 is responsible for transferring fat into liver cells while the second enzyme begins the oxidation process. A third enzyme, CPT1A, which is responsible for transporting fat into mitochondria, is also less available in obesity-prone rats.

The increasing numbers of obese and overweight people are often thought to be a result of a diet high in calories and carbohydrates. The new study results, available in the August issue of Metabolism, suggest a genetic impact on oxidation at the cellular level as a culprit in weight gain.

"The present findings point to fat oxidation in the liver as a target for the development of drugs that suppress appetite and promote weight loss in obese individuals," Friedman said.

Hmmmm...
Could this be why some of us don't lose very fast, even on low carb?
I wonder if there's a blood test or if you'd have to have a biopsy? Maybe Dr Mike will have something about this..
Or is this an instance where taking the tbs of apple cider vinegar before a meal actually has more merit? (Not taking away from acv at all, just wondering if it could help digest fat) Didn't we used to eat "bitters" to stimulate digestion?

I'm glad they're seeing a physical cause, but why is the solution to suppress appetite? Fats are needed. I would think they'd look at enzyme therapy to improve the digestion of fat. Your cells would still need more energy if it's unable to process the fat.

Which is exactly why I am on the Fat Flush plan.
This is not a new discovery! In the Fat flush book, Ann Louise Gittleman clearly devises a plan for detoxiflying the liver and gives it back the ability to metabolise fat. Her plan is still low carb, but also lower in fat.

I think I have her book. She recommends cranwater, right? I remember having a hard time finding "just" cranberry juice. I mean, she gives a brand name, but I had a hard time finding it around here.

And I have a horrible, from childhood, sweet tea in a bottle, addiction to caffeine..

Yes, she does say cran water which you can make yourself. You are allowed one cup of organic real coffee a day, but obviously the inference is on taking the stress off of the liver, and especially for women caffeine is very stressful on the liver. It also effects bone density....did you know that? They did a thingumy on over 80,000 women who drank various amounts of caffeine and the ones who drank more had greater incidence of bone fractures!

So far, my bones seem to be okay. I even got kicked by a horse while on my horse a few years ago. I still have a mark on my shin. I did get it x-rayed. It wasn't broke, I guess it was a bone bruise. I think I'll tell my husband about it though. He drinks even more than I do.

I'm also formulating a plan for when we eat out, which is often. I usually get unsweet tea. I've tried water before, but it's usually municipal and I'm used to our well. I'm thinking I'll look for bottled, but if they don't have that, I'll just ask for extra lemon!

I found my book (wonder of wonders) I hadn't gotten all the way through it. And we had some things going on, and it got forgotten. (cousin killed in Iraq, grandmother in hospital and now rehab. Uncle in hospital numerous times and they can't find why he's losing blood. Twenty year old daughter moved back in, sorta... Have to put my 11 year old dog to sleep due to cancer. I haven't done it yet, I need to do it next week.)

OMG 2bthinner! I though my life was stressful. Taking care of two elderly parents can be difficult at times, but not near as much as what you've been going through. God bless you.
You have plenty of time to finish reading a book, just hang in there and take care of yourself.

I suspect so, even on low calorie I don't lose very fast.
This is preliminary information, someday if it pans out there will be blood tests.

It isn't digesting fat, it's metabolising it as energy AFTER it has been digested.

We're probably very good at running off of glycogen but not good at running off of stored fat.

My doctor had me to do a special blood test a month ago. When he looked at the test result, he called me and said that something related to my liver showed small elevation which may indicate hepatitis. So he wanted me to repeat the test in 2-3 weeks.

When I told him that I'm on Atkins diet, he said that may be it. What he has seen could have been caused by the food I eat only meaning that my liver is fine.

After I repeated the test, he called me back and said that the last test result shows no problem with my liver.