title: High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.
abstract: Endometriosis is a benign gynecological condition that causes considerable morbidity due to associated infertility, debilitating pelvic pain and inflammatory dysfunctions. Diet is a highly modifiable risk factor for many chronic diseases, but its contribution to endometriosis has not been extensively investigated, due partly to the paradoxical inverse association between obesity and disease incidence. Nevertheless, chronic exposure to dietary high-fat intake has been linked to greater systemic inflammation and oxidative stress, both features of women with endometriosis. Here, we evaluated the effects of a high-fat diet (HFD) (45% fat kcal) on endometriosis progression using an immunocompetent mouse model where ectopic lesion incidence was induced in wild-type recipients by ip administration of endometrial fragments from transcription factor Krüppel-like factor 9-null donor mice. We show that HFD significantly increased ectopic lesion numbers in recipient mice with no significant weight gain and modifications in systemic ovarian steroid hormone and insulin levels, relative to control diet-fed (17% fat kcal) mice. HFD promotion of lesion establishment was associated with reductions in stromal estrogen receptor 1 isoform and progesterone receptor expression, increased F4/80-positive macrophage infiltration, higher stromal but not glandular epithelial proliferation, and enhanced expression of proinflammatory and prooxidative stress pathway genes. Lesion-bearing HFD-fed mice also displayed higher peritoneal fluid TNFα and elevated local and systemic redox status than control diet-fed counterparts. Our results suggest that HFD intake exacerbates endometriosis outcome in the absence of ovarian dysfunction and insulin resistance in mice and warrants further consideration with respect to clinical management of endometriosis progression and recurrence in nonobese patients.
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Heard
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Simmen
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: John Mark P
authors.initials: JM
authors.lastname: Pabona
authors.affiliation: Departments of Physiology and Biophysics (M.E.H., F.A.S., Y.Y., J.M.P.P., R.C.M.S.) and Pediatrics (S.B.M.) and Arkansas Children's Hospital Research Institute (S.B.M.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Department of Obstetrics and Gynecology (Y.Y.), The Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Rosalia C M
authors.initials: RC
authors.lastname: Simmen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D010084:Oxidation-Reduction