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

Mehmet M. Altintas, Maria A. Rossetti, Behzad Nayer, Alvaro Puig, Patricia Zagallo, Luis M. Ortega, Kevin B. Johnson, George McNamara, Jochen Reiser, Armando J Mendez, Ali Nayer

Research output: Contribution to journalArticle

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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-, 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- 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.

Original languageEnglish
Article number198
JournalLipids in Health and Disease
Volume10
DOIs
StatePublished - Nov 4 2011

Fingerprint

Mastocytosis
Obese Mice
Adipokines
Nutrition
Gene expression
Fats
Apoptosis
Diet
Gene Expression
Adipocytes
Caspase 3
Obesity
Adiponectin
Leptin
Macrophages
Mast Cells
Interleukin-10
Adipose Tissue
Interleukin-6
Genes

Keywords

  • adipokines
  • adipose tissue
  • apoptosis
  • crown-like structures
  • inflammation
  • macrophages
  • mast cells
  • Obesity

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice. / Altintas, Mehmet M.; Rossetti, Maria A.; Nayer, Behzad; Puig, Alvaro; Zagallo, Patricia; Ortega, Luis M.; Johnson, Kevin B.; McNamara, George; Reiser, Jochen; Mendez, Armando J; Nayer, Ali.

In: Lipids in Health and Disease, Vol. 10, 198, 04.11.2011.

Research output: Contribution to journalArticle

Altintas, Mehmet M. ; Rossetti, Maria A. ; Nayer, Behzad ; Puig, Alvaro ; Zagallo, Patricia ; Ortega, Luis M. ; Johnson, Kevin B. ; McNamara, George ; Reiser, Jochen ; Mendez, Armando J ; Nayer, Ali. / Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice. In: Lipids in Health and Disease. 2011 ; Vol. 10.
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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-, 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- 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.",
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AU - Nayer, Behzad

AU - Puig, Alvaro

AU - Zagallo, Patricia

AU - Ortega, Luis M.

AU - Johnson, Kevin B.

AU - McNamara, George

AU - Reiser, Jochen

AU - Mendez, Armando J

AU - Nayer, Ali

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N2 - 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-, 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- 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.

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KW - mast cells

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