One of the most serious health conditions in the developed world is the metabolic syndrome (MetS), a collection of disorders (such as obesity and insulin resistance) that lead to increased risk of developing type 2 diabetes and heart disease. A protein known as PPAR-gamma has been shown to be affect most aspects of MetS. However, these studies have had to focus on the affects of PPAR-gamma on one aspect of MetS at a time because mice lacking PPAR-gamma in all cells die before birth. But now, Richard Morentsen, David Milstone, and colleagues have generated viable mice with a global PPAR-gamma defect and determined how the individual affects of PPAR-gamma manifest in the whole mouse.

In the study, which appears online in advance of publication in the March print issue of the Journal of Clinical Investigation, the authors show that mice with a global PPAR-gamma defect are severely insulin resistant and have less fat than normal mice, although the latter is offset by an increase in the size of all the internal organs. These changes were associated with a decrease in blood pressure (hypotension), which is surprising given that PPAR-gamma - stimulating drugs (known as thiazolidinediones) used to treat type 2 diabetes also decrease blood pressure. These mice will therefore be useful for further investigating whether PPAR-gamma mediates the effects of thiazolidinediones in individuals with type 2 diabetes and/or MetS.

TITLE: Hypotension, lipodystrophy, and insulin resistance in generalized PPAR-gamma - deficient mice rescued from embryonic lethality

AUTHOR CONTACT:

Richard M. Mortensen
University of Michigan Medical School, Ann Arbor, Michigan, USA.

David S. Milstone
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.



JCI table of contents: February 15, 2006

Contact: Karen Honey
Journal of Clinical Investigation