Featured Research

from universities, journals, and other organizations

Liver fat gets a wake-up call that maintains blood sugar levels

Date:
May 6, 2012
Source:
University of Pennsylvania School of Medicine
Summary:
A research team reports that mice in which an enzyme called histone deacetylase 3 was deleted had massively fatty livers, but lower blood sugar, and were thus protected from glucose intolerance and insulin resistance, the hallmark of diabetes.

This image shows a high-fat-diet (HFD)-induced fatty liver in wild-type mice, characterized by big lipid droplets in liver cells (top). Liver-specific HDAC3 knockout mice on HFD, note that the lipid droplets become smaller even though the total lipid content is increased (bottom).
Credit: Mitchell Lazar, M.D., Ph.D.; Zheng Sun, Ph.D., Perelman School of Medicine, University of Pennsylvania; Nature Medicine

A Penn research team, led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, reports in Nature Medicine that mice in which an enzyme called histone deacetylase 3 (HDAC3) was deleted had massively fatty livers, but lower blood sugar, and were thus protected from glucose intolerance and insulin resistance, the hallmark of diabetes.

Related Articles


Insulin resistance occurs when the body does a poor job of lowering blood sugars. Typically, patients with obesity and type 2 diabetes have fatty livers, and the dogma in the field, says Lazar, is that the fatty livers contribute to the insulin resistance and diabetes in a vicious cycle. These findings are "a clear counterexample to this thinking," he says.

The researchers observed that the extra fat in the liver did not cause insulin resistance because it was sequestered in tiny lipid droplets inside individual liver cells, coated by a specific protein. The metabolites that would otherwise be used by the body to make glucose were re-routed to make fat, leading to reduced glucose in the bloodstream. The advantage of the lower blood sugar is tempered by the excess liver fat, which can lead to problems of its own, including liver failure.

Cells of high-fat-diet-induced fatty livers in wild-type mice were characterized by larger lipid droplets, but liver-specific HDAC3 knockout mice on a high-fat diet were characterized by smaller lipid droplets, even though the total lipid content increased versus the wild-type mice.

Why would the body have this re-routing process in the first place? The team looked to the circadian rhythm of the nocturnal mice for answers. When inactive during the day, mouse HDAC3 migrates to genes to turn off fat synthesis. This allows metabolites to make glucose for fueling the sleeping body. When waking, during the night, the mouse body makes a metabolic switch, anticipating the intake of food, and turns on fat synthesis for energy storage. The on-and-off cycle of HDAC3 is directly regulated by the internal circadian clock, and the system falls apart when HDAC3 is deleted.

The findings suggest that the cordoning off of lipids of the liver in many, tiny coated droplets helps to manage insulin resistance in the body. And, the findings cement the fact that HDAC3 is pivotal in integrating signals from the internal body clock to coordinate metabolism, especially in the liver, notes the first author Zheng Sun, PhD, postdoctoral fellow in the Lazar lab.

The findings demonstrate that fat itself is not necessarily all bad. "It matters a lot how fat is handled and stored," notes Lazar. "It also highlights the importance of complying with our internal circadian clock. For example, since our body does not anticipate food at night and is preparing to generate more glucose, night-time eating is likely to shoot up blood sugar and thus may contribute to diabetes."

The work was funded in part by National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK43806; P01 DK49210; R01 DK40936; R01 DK075017); the Cox Institute of Medical Research; and the JPB Foundation.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Zheng Sun, Russell A Miller, Rajesh T Patel, Jie Chen, Ravindra Dhir, Hong Wang, Dongyan Zhang, Mark J Graham, Terry G Unterman, Gerald I Shulman, Carole Sztalryd, Michael J Bennett, Rexford S Ahima, Morris J Birnbaum, Mitchell A Lazar. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nature Medicine, 2012; DOI: 10.1038/nm.2744

Cite This Page:

University of Pennsylvania School of Medicine. "Liver fat gets a wake-up call that maintains blood sugar levels." ScienceDaily. ScienceDaily, 6 May 2012. <www.sciencedaily.com/releases/2012/05/120506160121.htm>.
University of Pennsylvania School of Medicine. (2012, May 6). Liver fat gets a wake-up call that maintains blood sugar levels. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2012/05/120506160121.htm
University of Pennsylvania School of Medicine. "Liver fat gets a wake-up call that maintains blood sugar levels." ScienceDaily. www.sciencedaily.com/releases/2012/05/120506160121.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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