Featured Research

from universities, journals, and other organizations

High-altitude metabolism lets mice stay slim and healthy on a high-fat diet

Date:
April 16, 2010
Source:
University of California - San Diego
Summary:
Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found. While their normal littermates gain weight, develop fatty livers and become resistant to insulin, just like overweight humans do, the mutant mice suffered none of these ill effects.

Mice like the one on the left in this photo gain weight and show signs of ill health on a high fat diet while their mutant littermates stay slender.
Credit: Johnson Lab, UCSD

Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found.

"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.

The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said.

Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.

"We expected them to die as embryos," said Na Zhang, a graduate student in Johnson's lab and lead author of the study. "Then we saw they can survive for a long time."

"From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy," Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.

"We fed the mice with a very high fat diet -- 60 percent fat -- just to see how they would respond," Zhang said. "Mutants can eat a lot, but they didn't gain a lot of weight. They are less fatty around their middles compared with their littermates."

Obese people develop a "fatty liver," and so did the wild type littermates. The fat mice also developed high blood cholesterol with elevated levels of the "bad" type, LDL. In lean mutants, LDL increased much less.

"All of these observations support that the modified mice have better metabolic profiles," Zhang said.

The genetic manipulations disabled the FIH gene entirely. "In every tissue, in every cell, the protein is gone," Zhang said. But the scientists wanted to know what part of the mouse physiology was responsible for the changes, so they created new mice in which the FIH protein was deleted only in specific tissues: the nervous system or the liver.

Mice that were missing FIH only from their nervous system showed most of the same effects. "But if it was only deleted in the liver, then no." Zhang said.

Though smaller, the mutant mice eat and drink 30 to 40 percent more than wild-type mice.

"Where do those calories go? To heat generation and an increased heart rate." Johnson said. They also breathe heavily compared with normal mice, taking in 20 to 40% more air. "This deep breathing is like exercise for them."

The FIH protein is part of a wide system that responds to low levels of oxygen. The mice behave as if they are breathing thin air. When people travel to higher altitudes, they breathe heavily for a few days, then adjust by producing more oxygen-carrying blood cells. "These mice never adjust to the apparent low oxygen," Johnson said. "They stay in this acute phase of hypoxic response their whole lives."


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. Na Zhang, Zhenxing Fu, Sarah Linke, Johana Chicher, Jeffrey J. Gorman, DeeAnn Visk, Gabriel G. Haddad, Lorenz Poellinger, Daniel J. Peet, Frank Powell et al. The Asparaginyl Hydroxylase Factor Inhibiting HIF-1α Is an Essential Regulator of Metabolism. Cell Metabolism, 15 April 2010 DOI: 10.1016/j.cmet.2010.03.001

Cite This Page:

University of California - San Diego. "High-altitude metabolism lets mice stay slim and healthy on a high-fat diet." ScienceDaily. ScienceDaily, 16 April 2010. <www.sciencedaily.com/releases/2010/04/100415125936.htm>.
University of California - San Diego. (2010, April 16). High-altitude metabolism lets mice stay slim and healthy on a high-fat diet. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2010/04/100415125936.htm
University of California - San Diego. "High-altitude metabolism lets mice stay slim and healthy on a high-fat diet." ScienceDaily. www.sciencedaily.com/releases/2010/04/100415125936.htm (accessed April 17, 2014).

Share This



More Plants & Animals News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Change of Diet Helps Crocodile Business

Change of Diet Helps Crocodile Business

Reuters - Business Video Online (Apr. 16, 2014) Crocodile farming has been a challenge in Zimbabwe in recent years do the economic collapse and the financial crisis. But as Ciara Sutton reports one of Europe's biggest suppliers of skins to the luxury market has come up with an unusual survival strategy - vegetarian food. Video provided by Reuters
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Raw: Three Rare White Tiger Cubs Debut at Zoo

Raw: Three Rare White Tiger Cubs Debut at Zoo

AP (Apr. 16, 2014) The Buenos Aires Zoo debuted a trio of rare white Bengal tiger cubs on Wednesday. (April 16) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins