Navigation Links
Scripps Research Institute scientists find new calorie-burning switch in brown fat
Date:8/1/2014

LA JOLLA, CAAugust 1, 2014Biologists at The Scripps Research Institute (TSRI) have identified a signaling pathway that switches on a powerful calorie-burning process in brown fat cells.

The study, which is reported in this week's online Early Edition of the Proceedings of the National Academy of Sciences, sheds light on a process known as "brown fat thermogenesis," which is of great interest to medical researchers because it naturally stimulates weight loss and may also protect against diabetes.

"This finding offers new possibilities for the therapeutic activation of brown fat thermogenesis," said team leader Anastasia Kralli, associate professor in TSRI's Departments of Chemical Physiology and Cell Biology.

'Revving the Engines'

Most fat cells in our bodies are "white fat" cells that store fat as a reserve energy supply. But we and other mammals also have depots of "brown fat" cells. These apparently evolved not to store but to burn energyquickly, as a way of generating heat and keeping the body warm in cold conditions, as well as possibly to get rid of excess caloric intake.

Human babies as well as mammals that hibernate have relatively extensive brown fat tissues. Scientists have found in recent years that many adult humans have significant levels of brown fat, which are located mostly in the neck and shoulders, and appear to help regulate body weight and blood sugar.

Low temperatures activate the brown-fat thermogenesis process via the sympathetic nervous system: Nerve ends in brown fat tissue release the neurotransmitter norepinephrine, and that triggers a shift in metabolism within the brown fat cells, which are densely packed with tiny biological energy reactors called mitochondria.

"The mitochondria start generating heat instead of useful chemical energy; it's like revving the engines of a lot of parked cars," said first author Marin Gantner, who was a graduate student in the Kralli laboratory during the study.

Given the potential medical applicationsabout 100 million people suffer from obesity or diabetes in the US aloneresearchers are eager to understand brown fat thermogenesis and how it can be boosted artificially. One clue, reported by other scientists in 1998, is that norepinephrine instructs brown fat cells to express high levels of a protein called PGC-1α, which acts as a general amplifier of energy metabolism and also activates thermogenesis. The Kralli laboratory has shown in past studies that PGC-1α works by activating a molecule called ERRα. But this pathway can't be the only one that triggers thermogenesis, because mice lacking PGC-1α in their fat cells, or ERRα, still show most of the usual thermogenesis response to cold.

A Serendipitous Discovery

In the new study, Gantner, Kralli and their colleagues discovered another thermogenesis activation pathway that works alongside PGC-1α and ERRα.

Originally, however, they were not examining brown fat thermogenesis, but instead were looking for clues to the function of ERRβ, a protein about which little was known at the time, except that it was closely related to ERRα, appeared in brown fat cells, and also worked as a so-called nuclear receptora molecular switch for gene activation that can be turned on by small lipophilic molecules or a signaling protein partner.

In the hope of finding ERRβ's signaling partner, the team screened about 18,000 different proteins to see which could biochemically activate it. After accumulating a short list of "hits," the scientists found that one of them, GADD45γ, is normally produced in mouse brown fat cells and becomes especially abundant after exposure to coldhinting that GADD45γ and ERRβ, much like PGC-1α and ERRα, work together to switch on brown fat thermogenesis.

The team then detailed the signaling in this pathway, from cold-induced norepinephrine release, to upregulation of GADD45γ in brown fat cells, to the activation of ERRβ and another closely related protein, ERRγ, which turned out to be also prevalent in brown fat cells and relevant to thermogenesis. "We focused on ERRγ after that," Gantner said.

The team confirmed that the GADD45γ-mediated activation of ERRγ leads to the metabolic shift in brown fat mitochondria that is characteristic of thermogenesis. The scientists also found that transgenic mice lacking GADD45γ can't fully switch on thermogenesis under cold conditions.

In the experiments, GADD45γ acted synergistically with PGC-1α to activate brown fat cell activity. "You have to add them together to get the full effect," said Kralli, suggesting that ideally, one would stimulate both pathways to boost brown fat thermogenesis.


'/>"/>

Contact: Madeline McCurry Schmidt
madms@scripps.edu
858-784-9254
Scripps Research Institute
Source:Eurekalert  

Related biology news :

1. Scripps Florida scientists shed new light on nerve cell growth
2. Scripps Florida scientists uncover new compounds that could affect circadian rhythm
3. Scripps Research Institute scientists reveal molecular yin-yang of blood vessel growth
4. Scripps Research Institute chemists discover structure of cancer drug candidate
5. Scripps Florida scientists reveal molecular secrets behind resveratrols health benefits
6. Scripps Florida scientists find connection between gene mutation, key symptoms of autism
7. Microscopic organism plays a big role in ocean carbon cycling, Scripps scientists discover
8. Scripps Research Institute scientists provide new grasp of soft touch
9. Scripps Florida scientists offer best practices nutrition measurement for researchers
10. NIH grants up to $28 million to group led by Scripps Research for work on ebola treatment
11. Scripps Wellderly Genome Resource now available to researchers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scripps Research Institute scientists find new calorie-burning switch in brown fat
(Date:2/1/2016)... Feb. 1, 2016  Today, the first day of ... plans to develop a first of its kind workplace ... IBM Watson. In the first application of ... IBM ), and Welltok will create a new ... with cognitive analytics, delivered on Welltok,s health optimization platform. ...
(Date:1/25/2016)...   Unisys Corporation (NYSE: UIS ) today announced ... International Airport, New York City , to help ... to enter the United States using passports ... pilot testing of the system at Dulles last year. The ... during January 2016. --> pilot testing of the ...
(Date:1/21/2016)... --> ... report "Emotion Detection and Recognition Market by Technology (Bio-Sensors, NLP, ... Voice Recognition and Others), Services, Application Areas, End ... published by MarketsandMarkets, the global Emotion Detection and ... Billion by 2020, at a CAGR of 31.9%, ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... 2016 - New FDA action date of ... FDA action date of July 22, 2016   ... 22, 2016   - Lifitegrast has ... indicated for the treatment of signs and symptoms of dry eye ... potential to be the only product approved in the U.S. in the past decade indicated ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... Digital Forensics Club, takes place February 5-6 at the University’s student center, ... and activities such as workshops and competitions for ample networking, learning and ...
(Date:2/4/2016)... Columbia and MENLO PARK, Calif. ... (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused ... announced that it will present at the 18 th ... February 8, 2016 at 10:00 a.m. EST in ... , DelMar,s president and CEO, will provide an update on ...
(Date:2/4/2016)... -- Spherix Incorporated (Nasdaq: SPEX ) -- an intellectual property development ... property, today provided an update on the Company,s cases ... Texas and announcing that those ... Re-examination ("IPR") proceedings that VTech and Uniden filed ... on only certain claims of two of the patents ...
Breaking Biology Technology: