“We’re trying to figure out what the mechanism is—what it takes to make fat cells,” says Whitehead Founding Member Harvey Lodish, who is also a professor of biology and a professor of bioengineering at MIT. “The obvious reason we’re interested in this is because a lot of people have too many of them.”
According to the Centers for Disease Control and Prevention, obesity—having a body mass index (BMI) of 30 or higher—is a serious healthcare and economic problem in the United States. More than one-third of American adults are obese, a condition that can lead to heart disease, type 2 diabetes, and stroke. In 2008 obesity-related issues were estimated to cost $147 billion.
All of these problems are caused by an overabundance of white fat cells—adipose tissue cells that store excess energy as fat or lipid droplets. Unlike white fat cells, brown fat cells, which are most prevalent in babies and have a reduced presence in adults, use lipids as fuel to maintain a stable, warm body temperature. Understanding how both types of fat cells are formed and maintained may one day lead to anti-obesity therapies.
In the quest to understand fat-cell generation and maintenance, the Lodish lab scanned mouse fat cells to determine which of the cells’ long noncoding RNAs (lncRNAs) are active. Of the 175 identified, 10 lncRNAs were found to play significant roles in these cells.
Residing within what was once dubbed “junk DNA”, lncRNAs have recently gained fame as important gene expression regulators that modify chromatin, enhance transcription, and promote messenger RNA (mRNA) degradation, as well as through other methods that have yet to be elucidated. Recently, the Lodish lab identified lncRNAs as playing a vital role in regulating programmed cell death during one of the final stages of red blood cell differentiation.
To determine the function of the identified active lncRNAs in fat cells, Lei Sun, a former postdoctoral researcher in the Lodish lab, and Loyal Goff from Harvard University and the Broad Institute, knocked each lncRNA down individually in fat precursor cells and analyzed the results. When 10 of these lncRNAs had reduced expression, the cells did not turn on the genes that are usually expressed in mature white fat cells, and the cells had significantly smaller lipid droplets than white fat cells with normal lncRNA expression. Their work is reported in this week’s issue of the Proceedings of the National Academy of Sciences (PNAS).
“This is the first study showing the importance of lncRNAs for the regulation of adipogeneis,” says Sun, who is now an assistant professor at Duke-NUS Graduate Medical School. “Our understanding of lncRNA function in these cells is still incomplete, but in the future, this line of research may reveal new pathways that obesity drugs could target.”
This research was supported by National Institutes of Health (DK047618, DK068348, 5P01HL066105, and 1DP2OD00667), National Science Foundation, Damon Runyon Cancer Research Foundation, Agency of Science, Technology and Research, Singapore, Searle Scholars Program, Smith Family Awards Program, and Merkin Family Foundation.
Written by Nicole Giese Rura
Harvey Lodish’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.
“Long noncoding RNAs regulate adipogenesis”
PNAS, online the week of February 11, 2013.
Lei Sun (a,1), Loyal A. Goff (b,c,d,1), Cole Trapnell (b,c,1), Ryan Alexander (a,d), Kinyui Alice Lo (a,d), Ezgi Hacisuleyman (b,e), Martin Sauvageau (b,c,e), Barbara Tazon-Vega (b,c), David R. Kelley (b,c), David G. Hendrickson (b,c), Bingbing Yuan (a), Manolis Kellis (c,d), Harvey F. Lodish (a,f,g), and John L. Rinn (b,c,e).a. Whitehead Institute for Biomedical Research, Cambridge, MA 02142
1. These authors contributed equally to this work.
Nicole Giese Rura | Newswise
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences