http://www.ncbi.nlm.nih.gov/entrez/...6&dopt=Abstract
Clin Sci (Lond). 1997 Jan;92(1):3-11. Related Articles, Links
Regulation of adipose cell number in man.
Prins JB, O'Rahilly S.
1. Adipose tissue mass is dependent on both the average volume and the number of its constituent adipocytes. Significant alteration in body mass involves alteration in both adipocyte volume and number. 2. Increases in adipocyte number occur via replication and differentiation of preadipocytes, a process which occurs throughout life. Decreases in adipocyte number occur via preadipocyte and adipocyte apoptosis, and possibly adipocyte dedifferentiation. 3. Overall regulation of adipose mass involves endocrine, paracrine and possibly autocrine systems. Hypothalamic centres appear to control appetite, metabolic rate and activity levels in a co-ordinated manner. Within the hypothalamus, known weight regulatory molecules include glucagon-like peptide-1, neuropeptide Y and leptin. Leptin is a major afferent signal from adipose tissue to the hypothalamus, providing information on overall adipose tissue mass. However, the precise means by which the hypothalamus signals to adipose tissue is less well understood. 4. In adipose tissue, known molecular regulators of adipose cell number include insulin, ligands for the peroxisome proliferator activated receptor-gamma, retinoids, corticosteroids and tumour necrosis factor-alpha. The net effect of these and other regulators is to effect a concerted alteration in adipocyte volume and number. This review largely focuses on the control of fat cell acquisition and loss and the influence of these processes on adipose tissue mass and regional distribution. [This is the print version of story
http://www.abc.net.au/science/news/...s/s1317822.htm]
Fighting fat cell by cell
Judy Skatssoon
ABC Science Online
Wednesday, 9 March 2005
Targeting fat cells with drugs that stop them multiplying could help fight obesity (Image: iStockphoto)
A newly discovered protein that causes fat cells to multiply may be a future target for controlling obesity, say Australian researchers who have just started animal trials to block its action.
Professor John Prins of the University of Queensland says this protein, called fibroblast growth factor 1 or FGF-1, is also instrumental in causing cancer cells to proliferate, plays a role in skin and bone growth, and wound healing.
Prins' group has progressed since it reported the discovery of FGF-1 recently in the journal Diabetes.
Laboratory experiments have shown drugs that interfere with FGF-1 stop human fat cells multiplying. And the group is now trialling several drugs to block FGF-1 action in animal studies.
Some drugs that showed potential in the test tube are currently used to treat cancer, he says, because they stop the growth of new blood vessels that feed tumours.
Fat cells divide and conquer
Prins' story began 10 years ago with the discovery that fat cells, like other cells in human tissue, were capable of programmed cell death, or apoptosis, and regeneration.
He says it was possible to isolate immature cells, or fibroblasts known as pre-adipocytes from adipose tissue, or fat.
In a test tube, those immature fat cells could be encouraged to differentiate, or grow into mature fat cells capable of doing what fat cells are supposed to do, store fat.
He also found it was possible to manipulate the pre-adipocytes to either accelerate or inhibit their growth.
The finding contradicted the existing belief that human adults have a finite number of fat cells that either expand as they store excess fat or shrink as fat reserves are depleted.
"Changes in fat mass couldn't just be explained by changes in the size of cells, but by their recruitment and loss," Prins says.
In other words, the belief that a person was doomed to be butterball or a greyhound by virtue of the actual number of fat cells they were stuck with no longer held water.
Fighting fat
Dr Tim Gill, executive officer of the Australasian Society for the Study of Obesity, says the discovery that fat cells can differentiate has opened up new avenues for anti-obesity therapeutics.
But he says many factors contribute to obesity and controlling it is unlikely to be as easy as manipulating a single pathway.
Parents who feel guilty about predisposing their child to a life of being fat could take heart from the finding, he says.