1965-P: The Extracellular Matrix Modulates Adipocyte Thermogenic Capacity

Obesity is characterized by an increase in adipose mass and is the leading risk factor for type 2 diabetes. Increasing adipose thermogenic capacity, by activation of brown or beige fat, could be a treatment for metabolic diseases. Nevertheless, many approaches fail in maintaining transformed adipose tissue in vivo, in part, due to the limited understanding of how environmental factors control cell fate and maintenance. We have shown that mice with a null mutation in the laminin α4 exhibit resistance to obesity, enhanced expression of thermogenic fat markers (UCP1) in subcutaneous white adipose tissue (sWAT), increased energy expenditure and enhanced insulin sensitivity. The knockout (KO) of Lama4 results in complex changes in overall ECM composition. We used liquid chromatography/tandem mass spectrometry (LC/MS) to evaluate ECM composition in sWAT from wild type (WT)and KO mice. In addition to the expected absence of Lama4, collagen 1A1 (Col1A1) and collagen 3A1 (Col3A1) were significantly lower in KO mice. Also, integrins α7 (ITα7) and β1 (ITβ1) were dramatically reduced. Immunohistochemical staining confirmed lower levels of Itα7 in KO compared to WT mice (P Disclosure M.A. Gonzalez Porras: None. K. Stojkova: None. M.K. Vaicik: None. A.A. Goddi: None. R.N. Cohen: None. E. Brey: None.