Obesity is associated With insulin resistance and a mild chronic inflammation in adipose tissues. Recent Studies Suggested that GM3 ganglioside mediates dysfunction in insulin signaling. However, it has not been determined the ganglioside profiling in adipose tissues of obese animals. Here, we for the first time examined semi-quantitative ganglioside profiles in the adipose tissues of high fat- and high sucrose-induced obese, diabetic C57BL/6J mice by TLC and HPLC/mass spectrometry. In control adipose tissues GM3 dominated with traces of GM1 and GD1a; obesity led to a dramatic increase in GM2, GM1, and GD1 a with the GM3 content unchanged. Similar results were obtained in KK and KKAy mice. Adipocytes separated from stromal Vascular cells including macrophages contained more of those gangliosides in KKAy mice than in KK mice. These results underscore those gangliosides in the pathophysiology of obesity-related diseases. (C) 2008 Elsevier Inc. All rights reserved.