title: Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice.
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.
authors: Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors: Mehmet M
authors: MM
authors: Altintas
authors: Maria A
authors: MA
authors: Rossetti
authors: Behzad
authors: B
authors: Nayer
authors: Alvaro
authors: A
authors: Puig
authors: Patricia
authors: P
authors: Zagallo
authors: Luis M
authors: LM
authors: Ortega
authors: Kevin B
authors: KB
authors: Johnson
authors: George
authors: G
authors: McNamara
authors: Jochen
authors: J
authors: Reiser
authors: Armando J
authors: AJ
authors: Mendez
authors: Ali
authors: A
authors: Nayer
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D050154:Adiposity; D000818:Animals; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D015536:Down-Regulation; D004822:Epididymis / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008415:Mastocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size; D009928:Organ Specificity; D011897:Random Allocation; D053802:Tryptases / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C556062:IL10 protein, mouse; D015850:Interleukin-6; D020738:Leptin; C509190:Tpsb2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D053802:Tryptases