title: Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues.
abstract: Dysregulation of immune cells and/or altered inflammatory signaling have been implicated with reproductive dysfunction. Physiological changes leading to perturbations in the profile of immune cells and/or pro-inflammatory cytokines in or around female reproductive tissue could potentially have profound effects on ovarian function. Obesity is associated with chronic low-grade inflammation due, in part, to increased immune cell infiltration and inflammation in visceral adipose depots. This study investigated the impact of diet-induced obesity on immune cell infiltration and inflammation in peri-ovarian adipose tissue and mRNA expression of key inflammatory markers and microRNAs (miRs) in ovarian tissue. Six-week-old female C57Bl/6J mice were fed a standard chow or high-fat diet (HFD; 60% kcal fat) for approximately 7 months, at which time peri-ovarian adipose tissue and ovarian tissues were collected. Histological analysis of peri-ovarian adipose tissue from obese mice revealed increased (P < 0.05) adipocyte size and the presence of crown-like structures, the morphological presentation of infiltrating immune cells in adipose tissue, along with increases (P < 0.05) in the mRNA levels of markers of T-cells, activated macrophages, inflammatory cytokines, and chemokines. Ovarian mRNA levels of Il1b, Il6, Tnfa, p55, p75, Ccl2, Ikbkb, and Rela were higher in obese tissue (P < 0.05), with a strong trend (P = 0.06) for an increase in Nos2 and RELA protein. Additionally, ovarian miR125b and miR143 levels were decreased (P = 0.1). These data demonstrate that diet-induced obesity elevates expression of inflammatory-mediator genes in both the ovary and surrounding adipose depot, potentially negatively affecting ovarian function.
authors.affiliation: Department of Animal Science, Iowa State University, Ames, IA, 50011.
authors.forename: J
authors.initials: J
authors.lastname: Nteeba
authors.forename: L C
authors.initials: LC
authors.lastname: Ortinau
authors.forename: J W
authors.initials: JW
authors.lastname: Perfield
authors.forename: A F
authors.initials: AF
authors.lastname: Keating
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D010053:Ovary / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004041:Dietary Fats