title: Phospholipid makeup of the breast adipose tissue is impacted by obesity and mammary cancer in the mouse: Results of a pilot study.
abstract: Obesity, an established risk factor for breast cancer (BC), is associated with systemic inflammation. The breast contains adipose tissue (bAT), yet whether it plays a role in BC progression in obese females is being intensively studied. There is scarce knowledge on the lipid composition of bAT in health and disease. The purpose of this pilot study was: 1) to determine whether obesity and BC are associated with inflammatory changes in bAT 2) to analyze for the first time the lipid profile of bAT in obese and lean mammary tumor-bearing and normal mice. Syngeneic E0771 mammary tumor cells were implanted into the mammary fat pad of lean and diet-induced obese C57BL/6 mice. BATs were analyzed four weeks after tumor cell inoculation by immunohistochemistry and mass spectrometry. Phospholipids were identified and subjected to ratiometric quantification using a TSQ Quantum Access Max triple quadrupole mass spectrometer utilizing precursor ion scan or neutral ion loss scan employing appropriate class specific lipid standards in a two step quantification process. Four main classes of phospholipids were analyzed: phosphatidylcholines phosphatidylserines, phosphatidylethanolamines and phosphatidylinositols. Our results showed that bAT in obese (normal and tumor-bearing) mice contained hypertrophic adipocytes compared with their corresponding samples in lean mice; higher numbers of macrophages and crown-like structures were observed in obese tumor bearers compared to obese normal mice. BAT from normal obese mice revealed higher concentrations of phosphatidylethanolamines. Furthermore, bAT from tumor-bearing mice expressed higher phosphatidylcholines than that from non-tumor bearing mice, suggesting the presence of the tumor is associated with phosphatidylcholines. Conversion of phosphatidylethanolamines to phosphatidylcholines will be investigated in E0771 cells. Additional studies are projected to investigate macrophage activation by these specific classes of phospholipids. Occurrence of triglycerides and free fatty acids will be examined in bAT and similar lipidomic analyses will be carried out visceral adipose tissue, highly inflamed in obesity.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St, Miami, FL 33136, USA. Electronic address: m.margolis@med.miami.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Margolis
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA. Electronic address: op52@nova.edu.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Perez
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St, Miami, FL 33136, USA. Electronic address: mmartinez@sanjuanbautista.edu.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA. Electronic address: AMsantander@med.miami.edu.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Santander
authors.affiliation: Diabetes Research Institute, Department of Medicine, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA. Electronic address: amendez@med.miami.edu.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Holtz-2147, Miami, FL 33136, USA. Electronic address: mnadji@med.miami.edu.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nadji
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA. Electronic address: anayer@med.miami.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Nayer
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St, Miami, FL 33136, USA. Electronic address: sbhattacharya@med.miami.edu.
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: mtorroella@med.miami.edu.
authors.forename: Marta
authors.initials: M
authors.lastname: Torroella-Kouri
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D010865:Pilot Projects
chemical_list: D005227:Fatty Acids; D010743:Phospholipids
keywords: Breast cancer; Inflammation; Lipidomics; Macrophages; Obesity; Phospholipids