Fat-free diet reduces liver fat in fat-free mice

February 3, 2009

Researchers at UT Southwestern Medical Center have uncovered crucial clues about a paradoxical disease in which patients with no body fat develop many of the health complications usually found in obese people.

The findings in mice, appearing online today in Cell Metabolism,have led to the initiation of a National Institutes of Health-funded clinical trial to determine whether eating an extremely low-fat diet could prevent many of the metabolic complications brought on by lipodystrophy.

Lipodystrophies are metabolic disorders characterized by the selective loss of fat tissues and complications of insulin resistance. Scientists speculate that the condition could be caused by the failure of stem cells to become fat cells.

"These patients don't have fatty tissue, even inside their abdomen," said Dr. Abhimanyu Garg, professor of internal medicine at UT Southwestern and senior author of the study. "They basically lack all the fat we see in a typical person, but their livers are loaded with fat. That's a big problem because too much fat in the liver leads to liver damage.

"We cannot do anything to reverse fat loss, but our findings might lead to the development of new therapies for the metabolic complications of lipodystrophy, such as diabetes, fatty liver and high triglycerides," said Dr. Garg, an investigator in the Center for Human Nutrition.

Dr. Garg has been studying patients with lipodystrophies for more than 20 years. He and colleagues at UT Southwestern have led the way in identifying gene mutations responsible for several forms of lipodystrophy and in identifying novel therapeutic approaches for these patients.

In this study, researchers genetically engineered mice to lack a specific enzyme called AGPAT2, which is also lacking in humans with generalized lipodystrophy. Under normal conditions, AGPAT2 is involved in the production of fat in body fat cells. In 2002 Dr. Garg's lab found that the AGPAT2 gene is mutated in patients with congenital generalized lipodystrophy.

"We generated this mouse model to learn why humans with this type of lipodystrophy develop metabolic complications," Dr. Garg said.

The researchers found that mice without the AGPAT2 enzyme used a novel, previously uncharacterized pathway to synthesize fat in their liver. Dietary fat also contributed to fat accumulation in the liver. Typically, particles called chylomicrons carry dietary fat throughout the body and release it in peripheral tissues so that it can either be stored in adipose tissue for later use or immediately burned as energy by muscles. Normally, adipose tissue provides fatty acids for fat synthesis in the liver. In these lipodystrophic mice, however, the adipose tissue did not release the excess fatty acids and the dietary fat accumulated in the liver.

What is surprising about this, Dr. Garg said, is that the amount of fat stored in the liver dropped substantially when researchers put the lipodystrophic mice on a fat-free diet. "Just eliminating the dietary fat reduced liver triglycerides by approximately 50 percent," he said.

In addition to establishing a clinical trial, Dr. Garg said the next step is to study the stem cells from the mice with lipodystrophy in order to determine why their stem cells become bone and muscle but not fat.

Source: UT Southwestern Medical Center

Explore further: Mimicking diet changes of global travel reveals clues to gut health​

Related Stories

Early human diet explains our eating habits

August 31, 2015

Much attention is being given to what people ate in the distant past as a guide to what we should eat today. Advocates of the claimed palaeodiet recommend that we should avoid carbohydrates and load our plates with red meat ...

Atomic view of bacterial enzymes that help human digestion

July 31, 2015

A group of researchers at the University of Waterloo in Ontario, Canada has reached deep into the human gut, plucked out a couple enzymes produced by bacteria residing there and determined their biological activities and ...

Liver, dietary proteins key in fertility

February 1, 2011

When you think about organs with an important role in reproduction, the liver most likely doesn't spring to mind. But a new report in the February issue of Cell Metabolism, a Cell Press publication, shows that estrogen receptors ...

Recommended for you

Ancient genome from Africa sequenced for the first time

October 8, 2015

The first ancient human genome from Africa to be sequenced has revealed that a wave of migration back into Africa from Western Eurasia around 3,000 years ago was up to twice as significant as previously thought, and affected ...

New method facilitates research on fuel cell catalysts

October 8, 2015

While the cleaning of car exhausts is among the best known applications of catalytic processes, it is only the tip of the iceberg. Practically the entire chemical industry relies on catalytic reactions. Therefore, catalyst ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.