The Making Of A Fat Cell

The study finds that a hormonal cocktail routinely used in the labinduces a key genetic switch in the transition from fat-cell precursorsto full-blown fat, researchers at University of Michigan Life SciencesInstitute report in the September Cell Metabolism.

"The body needs fat cells, both as a storage depot for fueland as cells that sense hormonal and energy status and in response,secrete hormones that maintain whole-body energy balance," said studyauthor Alan Saltiel. "However, you don't want too many, big fat cells.It's a careful balance, and many diseases are associated with eitherextreme."

Lipodystrophies are disorders characterized by fat deficiency,Saltiel said. While obesity and lipodystrophy represent opposite endsof the spectrum, both are characterized by other metabolic disorders,such as insulin resistance, he added.

The generation of fat begins before birth and continuesthroughout life. The first step in fat production involvesproliferation of mesenchymal stem cells, followed by differentiationinto fat cell precursors called preadipocytes. Mesenchymal stem cellscan differentiate into various cell types, including bone, cartilage,muscle, nerve, and fat.

Fat precursor cells then migrate and proliferate at the site offat production, where they differentiate further to become sphericaladipocytes.

"The multistep process is regulated by numerous hormones andis accompanied by dramatic changes in cell shape and gene expression,"Saltiel said.

The team identified changes in the activity of hundreds ofgenes during the transition to fat cells, including a critical switchin gene activity--from integrin alpha 5 to integrin alpha 6. Thatswitch allows preadipocytes to cease dividing and cluster, forming bonafide fat cells.

Integrins are a superfamily of cell surface proteins that areinvolved in binding to the extracellular matrix, a meshwork of proteinand fiber supports outside of cells that can influence their behavior.

"Fat cells require contact in order to stretch and changeshape--becoming round cells able to accumulate lots of lipids," saidSaltiel. "Many things happen in the generation of fat cells, thetransition from one integrin to another is a crucial step."

While there is no evidence as yet to suggest that changes inintegrin function underlie metabolic disorders, the fullerunderstanding of what happens in fat formation opens new avenues forexploration, he said.

The researchers include Jun Liu, Stephanie M. DeYoung, Ming Zhang,Mei Zhang, Alan Cheng, and Alan R. Saltiel of the University ofMichigan Life Sciences Institute, Ann Arbor, Michigan. This work wassupported by National Institutes of Health (NIH) grants. M.Z. wassupported by National Institute of Diabetes and Digestive and KidneyDiseases (NIDDK) postdoctoral National Research Service Award (NRSA)fellowship. This work also utilized the Cell and Molecular Biology Coreof the Michigan Diabetes Research and Training Center funded by NIH..

Liu et al.: "Changes in Integrin Expression During AdipocyteDifferentiation" Publishing in Cell Metabolism, Vol. 2, September 2005,pages 165-177. DOI 10.1016/j.cmet.2005.08.006 www.cellmetabolism.org