Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


The link between fasting and acute attacks of porphyria


A team of researchers has discovered a molecular missing link that helps explain why fasting brings on acute attacks of the genetic disease hepatic porphyria, according to a new report in the 26 August issue of the journal Cell. The finding could help improve treatments for those suffering from the disease, which may have been the culprit behind the "madness" of King George III of England.

Porphyria disease is caused by defects in the enzyme pathway that produces heme, a critical iron compound found throughout the body, most notably in red blood cells. The defects lead to the overproduction and toxic accumulation of the intermediate molecules that eventually become heme. Researchers and physicians have long known that fasting can cause acute attacks of the disease, and that the attacks can be relieved with glucose or other high-carbohydrate treatments, but the exact link between fasting and the attacks has been mysterious until now.

In the Cell study, Bruce Spiegelman of the Dana-Farber Cancer Institute and Harvard Medical School and colleagues show that fasting increases levels of a metabolic protein called PGC-1a. The "starvation" signal that fasting sends throughout the body prompts PGC-1a to jump-start the process of creating glucose from scratch in the liver. However, PGC-1a also regulates the activity of an enzyme called ALAS-1, the first key enzyme in the heme production pathway.

The higher levels of PGC-1a produce higher levels of ALAS-1, leading to a toxic buildup of precursor heme molecules, Spiegelman and colleagues found.

The finding explains why glucose infusions are helpful in treating acute attacks since the glucose boost can shut off the starvation signal and return PGC-1a levels back to normal.

However, the discovery could pave the way for new porphyria therapies that focus on PGC-1a itself rather that relying on high-carbohydrate treatments, the researchers suggest.

"Unfortunately, because of the therapeutic high carbohydrate intake, patients with hepatic porphyrias are prone to weight gain. Losing excess weight is very difficult for some of these patients because of fasting-induced acute attacks. Hopefully, our findings described here might lead to the development of more specific treatments for these patients," Spiegelman and colleagues say.

However, since fasting boosts PGC-1a levels, "it is also important that patients not fast or strongly diet," Spiegelman adds.

The researchers tested the link between PGC-1a and ALAS-1 in mice engineered to lack PGC-1a in the liver. In these mice, ALAS-1 levels did not rise as dramatically as in normal mice after fasting or after chemical treatment that mimicked some of the enzyme defects in genetic porphyria.

Although drugs like alcohol and barbiturates can also provoke an acute porphyria attack, PGC-1a is not involved in attacks brought on by barbiturates, Spiegelman and colleagues found after examining the effects of phenobarbital in both normal mice and mice without PGC-1a in their livers.

Acute porphyria attacks can include severe abdominal pain, skin sensitivity to sunlight, and psychiatric disorders like hysteria, which may have been the source of King George III’s well-known insanity, according to some historians.

Heidi Hardman | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Strong, steady forces at work during cell division
20.10.2016 | University of Massachusetts at Amherst

nachricht Disturbance wanted
20.10.2016 | Max Delbrück Center for Molecular Medicine in the Helmholtz Association

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Innovative technique for shaping light could solve bandwidth crunch

20.10.2016 | Physics and Astronomy

Finding the lightest superdeformed triaxial atomic nucleus

20.10.2016 | Physics and Astronomy

NASA's MAVEN mission observes ups and downs of water escape from Mars

20.10.2016 | Physics and Astronomy

More VideoLinks >>>