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Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice

Mehmet M Altintas1, Maria A Rossetti2, Behzad Nayer3, Alvaro Puig1, Patricia Zagallo1, Luis M Ortega1, Kevin B Johnson2, George McNamara4, Jochen Reiser1, Armando J Mendez2 and Ali Nayer1*

Author Affiliations

1 Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA

2 Diabetes Research Institute and Division of Endocrinology, Diabetes and Metabolism, University of Miami, Miami, FL, USA

3 College of Engineering, University of Miami, Coral Gables, FL, USA

4 Analytical Imaging Core Facility, Diabetes Research Institute, and UM/Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

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Lipids in Health and Disease 2011, 10:198  doi:10.1186/1476-511X-10-198

Published: 3 November 2011

Abstract

Background

Obesity is characterized by increased cell death and inflammatory reactions in the adipose tissue. Here, we explored pathophysiological alterations taking place in the adipose tissue in long-standing obesity. In the epididymal fat of C57BL/6 mice fed a high-fat diet for 20 weeks, the prevalence and distribution of dead adipocytes (crown-like structures), mast cells (toluidine blue, mMCP6), macrophages (F4/80), and apoptotic cells (cleaved caspase-3) were measured. Moreover, gene and/or protein expression of several adipocytokines (leptin, adiponectin, TNF-α, IL-10, IL-6, MCP-1), F4/80, mMCP6, cleaved caspase-3 were determined.

Results

We observed that the epididymal fat mass was lower in obese than in lean mice. In obese mice, the epididymal fat mass correlated inversely with body weight and liver mass. Dead adipocytes, mast cells, macrophages, and apoptotic cells were abundant in the epididymal fat of obese mice, especially in the rostral vs. caudal zone. Accordingly, mMCP6, F4/80, and cleaved caspase-3 gene and/or protein expression was increased. Conversely, adiponectin, leptin, IL-6, and MCP-1 gene expression levels were lower in the epididymal fat of obese than lean mice. Although TNF-α and IL-10 gene expression was higher in the epididymal fat of obese mice, their expression relative to F4/80 and mMCP6 expression were lower in the heavily infiltrated rostral than caudal zone.

Conclusions

This study demonstrates that in mice with long-standing obesity diminished gene expression of several adipocytokines accompany apoptosis and reduced mass of the epididymal fat. Our findings suggest that this is due to both increased prevalence of dead adipocytes and altered immune cell activity. Differential distribution of metabolically challenged adipocytes is indicative of the presence of biologically diverse zones within the epididymal fat.

Keywords:
Obesity; adipose tissue; inflammation; mast cells; macrophages; crown-like structures; apoptosis; adipokines