Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice.
BACKGROUND
Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver) and lymphatic (abdominal lymph nodes, spleen, and thymus) organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α), a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining.


RESULTS
ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-α. The proportion of mast cells immunoreactive for TNF-α was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was noted between ob/ob and control mice.


CONCLUSIONS
This study demonstrates that leptin deficiency-induced obesity is accompanied by alterations in the density of mast cells in abdominal fat depots. The divergent distribution of mast cells in subcutaneous versus visceral fat might partially account for their differential biological behavior. Mast cells might also play a role in adaptive immune response occurring in regional lymph nodes in obesity.
Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
Mehmet M
MM
Altintas
Behzad
B
Nayer
Eric C
EC
Walford
Kevin B
KB
Johnson
Gabriel
G
Gaidosh
Jochen
J
Reiser
Nestor
N
De La Cruz-Munoz
Luis M
LM
Ortega
Ali
A
Nayer
D050153:Abdominal Fat / Q000473:pathology*; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose; D002452:Cell Count; D002784:Cholesterol / Q000097:blood; D004822:Epididymis / Q000276:immunology / Q000473:pathology; D020738:Leptin / Q000172:deficiency*; D008099:Liver / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000473:pathology*; D009928:Organ Specificity; D019009:Proto-Oncogene Proteins c-kit; D013154:Spleen / Q000473:pathology; D050151:Subcutaneous Fat / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001786:Blood Glucose; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D019009:Proto-Oncogene Proteins c-kit