Fat cells step in to help liver during fasting

March 17, 2017
A UT Southwestern study determined that the metabolite uridine helps the body regulate glucose. This graphic depicts how the body’s fat cell-liver-uridine axis works to maintain energy balance. Credit: UT Southwestern Medical Center

How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? The answer may require rewriting some textbooks.

In a study published today in Science, UT Southwestern Medical Center researchers report that "have the liver's back," so to speak, to maintain tight regulation of (blood sugar) and uridine, a metabolite the body uses in a range of fundamental processes such as building RNA molecules, properly making proteins, and storing glucose as energy reserves. Their study may have implications for several diseases, including diabetes, cancer, and neurological disorders.

Metabolites are substances produced by a metabolic process, such as glucose generated in the metabolism of complex sugars and starches, or amino acids used in the biosynthesis of proteins.

"Like glucose, every cell in the body needs uridine to stay alive. Glucose is needed for energy, particularly in the brain's neurons. Uridine is a basic building block for a lot of things inside the cell," said Dr. Philipp Scherer, senior author of the study and Director of UT Southwestern's Touchstone Center for Diabetes Research.

"Biology textbooks indicate that the liver produces uridine for the circulatory system," said Dr. Scherer, also Professor of Internal Medicine and Cell Biology. "But what we found is that the liver serves as the primary producer of this metabolite only in the fed state. In the fasted state, the body's fat cells take over the production of uridine."

Basically, this method of uridine production can be viewed as a division of labor. Researchers found that during fasting, the liver is busy producing glucose – and so fat cells take over the role of producing uridine for the bloodstream. These findings were replicated in human, mouse, and rat studies.

Although uridine has many roles, this study is the first to report that fat cells produce plasma uridine during fasting and that a fat cell-liver-uridine axis regulates the body's energy balance.

Study lead author Dr. Yingfeng Deng, Assistant Professor of Internal Medicine, found that blood uridine levels go up during fasting and down when feeding. During feeding, the liver reduces uridine levels by secreting uridine into bile, which is transferred to the gallbladder and then sent to the gut, where it helps in the absorption of nutrients.

"It turns out that having uridine in your gut helps you absorb glucose; therefore uridine helps in glucose regulation," Dr. Scherer said.

The uridine in the blood works through the hypothalamus in the brain to affect another tightly regulated system – body temperature, Dr. Scherer added. It appears that only uridine made by fat cells reduces body temperature, he said.

Among the study's other key findings:

Blood uridine levels are elevated during fasting and drop rapidly during feeding. Excess uridine is released through the bile.

The liver is the predominant uridine biosynthesis organ, contributing to blood uridine levels in the fed state.

The fat cells dominate uridine biosynthesis and blood levels in the fasted state.

The fasting-induced rise in uridine is linked to a drop in driven by a reduction in the metabolic rate.

In dietary studies, the researchers found that prolonged exposure to a high-fat diet blunted the effects of fasting on lowering body temperature, an effect also associated with obesity. Further testing indicated those findings were due to the reduced elevation in uridine in response to fasting, said Dr. Deng, also a member of the Touchstone Diabetes Center.

Future research questions include studying the effects of feeding-induced reductions in uridine levels in organs that rely heavily on uridine from plasma, such as the heart, and whether bariatric surgery affects blood uridine levels.

"Our studies reveal a direct link between temperature regulation and metabolism, indicating that a uridine-centered model of energy balance may pave the way for future studies on uridine balance and how this process is dysregulated in the diabetic state," Dr. Scherer said.

Explore further: Size matters when it comes to keeping blood sugar levels in check

More information: Yingfeng Deng et al. An adipo-biliary-uridine axis that regulates energy homeostasis, Science (2017). DOI: 10.1126/science.aaf5375

Related Stories

Size matters when it comes to keeping blood sugar levels in check

February 10, 2017
Keeping blood sugar levels within a safe range is key to managing both type 1 and type 2 diabetes. In a new finding that could lead to fewer complications for diabetes patients, Yale School of Medicine researchers have found ...

New technique sheds light on RNA: Researchers develop method that could enhance gene sequencing data

January 28, 2013
Researchers at the University of Michigan Comprehensive Cancer Center have developed a technique to better understand why RNA may be different in cancer cells than in normal cells. The technique will bring new depth of understanding ...

Lipid enzyme heightens insulin sensitivity, potential therapy to treat Type 2 diabetes

July 16, 2015
Reducing high concentrations of a fatty molecule that is commonly found in people with diabetes and nonalcoholic fatty liver disease rapidly improves insulin sensitivity, UT Southwestern Medical Center diabetes researchers ...

Team identifies key protein causing excess liver production of glucose in diabetes

September 28, 2011
Researchers at the John G. Rangos Sr. Research Center at Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine have identified a powerful molecular pathway that regulates the liver's ...

Recommended for you

Personalized blood sugar goals can save diabetes patients thousands

December 11, 2017
A cost analysis by researchers at the University of Chicago Medicine shows treatment plans that set individualized blood sugar goals for diabetes patients, tailored to their age and health history, can save $13,546 in health ...

Kidney disease increases risk of diabetes, study shows

December 11, 2017
Diabetes is known to increase a person's risk of kidney disease. Now, a new study from Washington University School of Medicine in St. Louis suggests that the converse also is true: Kidney dysfunction increases the risk of ...

Type 2 diabetes is not for life

December 5, 2017
Almost half of the patients with Type 2 diabetes supported by their GPs on a weight loss programme were able to reverse their diabetes in a year, a study has found.

Skipping breakfast disrupts 'clock genes' that regulate body weight

November 30, 2017
Irregular eating habits such as skipping breakfast are often associated with obesity, type 2 diabetes, hypertension and cardiovascular disease, but the precise impact of meal times on the body's internal clock has been less ...

Type 2 diabetes has hepatic origins

November 28, 2017
Affecting as many as 650 million people worldwide, obesity has become one of the most serious global health issues. Among its detrimental effects, it increases the risk of developing metabolic conditions, and primarily type ...

Critical link between obesity and diabetes has been identified

November 28, 2017
UT Southwestern researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight that afflicts more than 30 million Americans and over 400 million ...

0 comments

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.