Navigation Links
Single cell studies identify coactivator role in fat cell maturation
Date:1/10/2011

HOUSTON - (Jan. 10, 2011) All fat cells are not the same a fact that has implications in the understanding and treatment of type 2 diabetes and obesity, said researchers from Baylor College of Medicine (www.bcm.edu) in a report that appears in the current issue of the Journal of Cell Biology (http://www.jcb.rupress.org/).

The amount of fat in each cell and the central transcription factor, PPAR gamma (peroxisome proliferator activated receptor gamma), can vary widely, but the fat cells (adipocytes) can maintain stable levels of master switches known as steroid receptor coactivators (SRC)-2 and -3, said Dr. Sean M. Hartig, a postdoctoral fellow, and Dr. Michael Mancini (http://www.bcm.edu/mcb/?PMID=9330), an associate professor of molecular and cellular biology at BCM and the director of the Integrated Microscopy Core at BCM (http://www.bcm.edu/microscopy/). Hartig is first author and Mancini senior author of the report.

"The difference was the SRCs," said Hartig. "They control the transcriptional switch for PPAR gamma to maximize fat accumulation."

PPAR gamma is known to regulate the production of adipocytes or fat cells. It regulates transcription making an RNA copy of DNA, which is the first step in gene expression.

"Our research shows that there isn't always a linear connection between this transcriptional regulator PPAR gamma and the lipid in a cell," said Mancini. "It's dogma that one equals the other, but as you dive into the population of cells using high throughput microscopy and with custom-built software 'pipelines,' you find lots of exceptions. Then Sean (Hartig) connected it to the coregulators."

New drug-screening technology that automates both microscopy and image analysis allows experts like Mancini and Hartig to collect pictures and quantify thousands of cells in a short period of time. In this case, it allowed them to analyze the composition of different populations of human fat cells.

"Sean measured the amount of lipid in every cell," said Mancini. "This new technology uses fluorescent dyes and antibodies and enabled him to quantify both the amount of fat in each cell, but also how much of the transcriptional regulator PPAR gamma was expressed."

"There was a continuum," said Hartig. "There were cells that did not have any PPAR gamma but still had somehow become adipocytes. There were cells that had increased levels of PPAR gamma but had never developed the characteristics of adipocytes."

The finding supports the theory that these cells represent a continuum of factors with modulated levels of PPAR gamma and lipids. "PPAR-equals-fat simply didn't hold up to this level of scrutiny," Mancini said.

Mancini pointed to a population of cells with high lipid levels and low levels of PPAR gamma. There were cells with the opposite situation.

Hartig said reduced levels of SRC-2 and 3 resulted in more cells with low levels of lipid and increased PPAR gamma.

This is important because some drugs used to treat type 2 diabetes increase the activity of PPAR gamma. These include the thiazolidines such as Actos and Avandia, which increase the levels of genes associated with sensitivity to insulin. However, because PPAR gamma stimulates fat cell production, these drugs can also lead to increased abdominal fat and, more recently, cardiovascular complications.

"If you could find a way to increase the proportion of cells that have PPAR gamma but don't accumulate lipids, you might have a positive outcome. That would probably require a drug with a different structure," said Mancini.

The automated microscopy makes it possible to monitor the effects of drugs on different populations of a large number of cells, said Mancini.

"Had we not been able to analyze the cell-to-cell differences, we would not necessarily have understood how this favorable switch controlling PPAR gamma transcriptional activity might manifest itself. Identification of compounds that target the SRC and PPAR gamma interface might be alternatives to current therapeutic strategies for type 2 diabetes," said Hartig.


'/>"/>

Contact: Dipali Pathak
pathak@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

Related biology news :

1. Iowa State, Ames Lab researcher develops new way to study single biological molecules
2. Single parenthood doesnt pay off for plants
3. Study shows a single shot of morphine has long lasting effects on testosterone levels
4. NIH renews Nanomedicine Center focused on treating single-gene disorders for $16.1 million
5. JFK single-gunman theory shot down by science
6. U-M researchers receive largest single collection of psoriasis DNA samples
7. Scared snails opt for single parenthood rather than wait for a mate
8. Single cell injections
9. Math model of colon inflammation singles out dangerous immune cells
10. Biosensors reveal how single bacterium gets the message to split into a swimming and a stay-put cell
11. Single-molecule manipulation for the masses
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2016)... , March 23, 2016 ... Interesse erhöhter Sicherheit Gesichts- und Stimmerkennung mit ... Inc. (NASDAQ: MESG ), ein ... dass das Unternehmen mit SpeechPro zusammenarbeitet, um ... der Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, im ...
(Date:3/21/2016)... Massachusetts , March 22, 2016 ... facial recognition with passcodes for superior security   ... ), a leading provider of secure digital communications services, ... their biometric technology and offer enterprise customers, particularly those ... secure facial recognition and voice authentication within a mobile ...
(Date:3/15/2016)... 2016 --> --> ... Market Research "Digital Door Lock Systems Market - Global Industry ... the global digital door lock systems market in terms of ... is forecast to grow at a CAGR of 31.8% during ... medium enterprises (MSMEs) across the world and high industrial activity ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... ... May 26, 2016 , ... ... Medistem Panama Inc. at the City of Knowledge in Panama, a 6 ... cells in the US earlier this year following FDA approval of a second ...
(Date:5/25/2016)... (PRWEB) , ... May 25, 2016 , ... ... features a variety of fracture-specific plating options designed to address fractures of the ... fracture fixation solutions. , The Acumed Ankle Plating System 3 is composed of ...
(Date:5/25/2016)... (PRWEB) , ... May 25, 2016 , ... Lady had ... she tore her cruciate ligament in her left knee. Lady’s owner Hannah sought the ... central Florida board-certified veterinary surgeon, to repair her cruciate ligament and help with the ...
(Date:5/24/2016)... ... May 24, 2016 , ... ... identity. The new Media Cybernetics corporate branding reflects a results-driven revitalization for a ... image analysis. The re-branding components include a crisp, refreshed logo and a new ...
Breaking Biology Technology: