Liver fat gets a wake-up call that maintains blood sugar levels
May 6, 2012 in Medical research
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.
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."
Provided by
University of Pennsylvania School of Medicine
-
Coordinating the circadian clock: Researchers find that molecular pair controls time-keeping and fat metabolism
Apr 04, 2012 |
not rated yet |
0
-
Penn Study Explains Paradox of Insulin Resistance Genetics
Oct 25, 2011 |
not rated yet |
0
-
Molecules work the day shift to protect the liver from accumulating fat (w/ Video)
Mar 10, 2011 |
not rated yet |
0
-
Fatty liver may herald impending type 2 diabetes
Feb 24, 2011 |
not rated yet |
0
-
Fatty livers are in overdrive
Dec 06, 2011 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
How can there be a term called "intestinal metaplasia" of stomach
7 hours ago
-
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013
-
If you became brain-dead, would you want them to pull the plug?
May 17, 2013
-
MRI bill question
May 15, 2013
-
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013
-
Alcohol and acetaminophen
May 13, 2013
- More from Physics Forums - Medical Sciences
More news stories
Common food supplement fights degenerative brain disorders
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research
1 hour ago |
5 / 5 (1) |
0
|
Finding a family for a pair of orphan receptors in the brain
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research
2 hours ago |
not rated yet |
0
|
Insight into the dazzling impact of insulin in cells
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research
2 hours ago |
4.5 / 5 (2) |
0
|
Do men's and women's hearts burn fuel differently?
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research
5 hours ago |
not rated yet |
0
Study suggests new source of kidneys for transplant
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research
21 hours ago |
5 / 5 (2) |
0
|
B vitamins could delay dementia
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
Enrichment therapy effective among children with autism, study finds
Children with autism showed significant improvement after six months of simple sensory exercises at home using everyday items such as scents, spoons and sponges, according to UC Irvine neurobiologists.
Poliovirus vaccine trial shows early promise for recurrent glioblastoma
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
'Doctor shopping' by obese patients negatively affects health
Overweight and obese patients are significantly more likely than their normal-weight counterparts to repeatedly switch primary care doctors, a practice that disrupts continuity of care and leads to more emergency room visits, ...
Aggressive behavior linked specifically to secondhand smoke exposure in childhood
Children who are exposed to secondhand smoke in early childhood are more likely to grow up to physically aggressive and antisocial, regardless of whether they were exposed during pregnancy or their parents have a history ...
If you can remember it, you can remember it wrong
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
May 07, 2012
Rank: not rated yet