Metabolism protein found to also regulate feeding behavior in the brain

February 26, 2016
Metabolism protein found to also regulate feeding behavior in the brain
Scientists found evidence of the metabolism-regulating protein amylin, shown in red, present in multiple regions throughout a brain area called the hypothalamus. Experiments suggest amylin produced by hypothalamic neurons helps reduce food consumption together with leptin.

The molecular intricacies of hunger and satiety, pivotal for understanding metabolic disorders and the problem of obesity, are not yet fully understood by scientists. However, new research from The Rockefeller University reveals an important new component of the system responsible for regulating food intake: a hormone called amylin, which acts in the brain to help control consumption.

"How much a person eats is regulated by a complex circuit, and in order to understand it, we need to identify all the molecules involved," says Jeffrey Friedman, Marilyn M. Simpson Professor and head of the Laboratory of Molecular Genetics at Rockefeller. "Amylin caught our attention when we were profiling a set of neurons in the hypothalamus, a part of the brain known to be involved in feeding behavior. Because it plays a role in sugar metabolism elsewhere in the body, we were interested in exploring its function in the brain."

What stops us from eating too much?

Friedman is well-known for his 1994 discovery of the hormone leptin, one regulator in this process. Defects in production are associated with obesity. However, treating obesity with leptin alone has not proven effective except in cases of severe leptin deficiency, suggesting that additional components are involved in this system.

The findings, published recently in Cell Metabolism, suggest that leptin and amylin work in concert to control and body weight.

Friedman and colleagues first identified the precursor to amylin—called Iselt amyloid peptide (Iapp)—in the brain by using a technology known as translating ribosome affinity purification, previously developed by fellow Rockefeller scientists. The researchers found that Iapp is abundant in multiple regions throughout the hypothalamus. (Incidentally, these findings contradict previous results, suggesting that prior experiments, which have not consistently found amylin in the brain, may not have used techniques sensitive enough to detect Iapp.)

To tease out the function of amylin in the hypothalamus, the researchers assessed its presence in mice that were obese due to leptin deficiency. When these mice were given leptin, their Iapp levels increased significantly, indicating that leptin regulates the expression of amylin.

Molecular teamwork

"We also looked directly at how amylin and leptin affect feeding behavior," says lead author Zhiying Li, a research associate in the lab. "When we give leptin to mice, it significantly suppresses food intake. However, when we give leptin to mice in which amylin is rendered nonfunctional with an inhibitor, the effect of leptin is blunted. This means that leptin and amylin are working together in a way that reduces feeding."

Additionally, the researchers evaluated how amylin controls neural signals. From recordings of neuron signals showing that leptin and amylin act on the same neurons in similar ways, they hypothesize that these hormones act in a synergistic manner, working together to produce an enhanced neural signal.

"These findings confirm a functional role for amylin in the central nervous system, and provide a potential mechanism to treat obesity more effectively, through combination therapy," says Friedman. "While this is a piece of the puzzle, we still need a better understanding of the cellular mechanisms involved in this system, which could provide new approaches that involve improved leptin signaling and sensitivity."

Explore further: Researchers come up with new answers concerning a weight-regulating hormone

More information: Zhiying Li et al. Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake, Cell Metabolism (2015). DOI: 10.1016/j.cmet.2015.10.012

Related Stories

Researchers come up with new answers concerning a weight-regulating hormone

February 11, 2016
For years, scientists have failed to locate the DNA variants that control the weight-regulating hormone, leptin. However, new research has enabled the identification of four genes associated with leptin levels, which is particularly ...

Leptin also influences brain cells that control appetite, study finds

June 1, 2014
Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of ...

Obesity research finds leptin hormone isn't the overeating culprit

May 15, 2015
For years, scientists have pointed to leptin resistance as a possible cause of obesity. Research led by investigators at the University of Cincinnati (UC) Metabolic Diseases Institute, however, found that leptin action isn't ...

From brain, to fat, to weight loss

September 24, 2015
Weight is controlled by the hormone leptin, which acts in the brain to regulate food intake and metabolism. However, it was largely unknown until now, how the brain signals back to the fat tissue to induce fat breakdown. ...

Leptin suppresses the rewarding effects of running

September 14, 2015
(HealthDay)—Leptin appears to inhibit running reward via signal transducer and activator of transcription-3 (STAT3), according to an experimental study published online Sept. 1 in Cell Metabolism.

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Feb 27, 2016
People tend to eat until their stomach is full, that is, until they *can't* eat any more. This total lack of self control which is at the same level as controlling one's bowels and bladder can only be stopped by making the stomach smaller so that these people can still eat as much as they can possibly stuff into their mouths without putting on any more weight.

Parents need to both demonstrate constraint and wean their children off overindulgence in the same way that they toilet train them, another basic self discipline behaviour.

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.