title: Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet.
abstract: Removal of the parametrial fat pads (partial lipectomy) from female SKH-1 mice fed a high-fat diet inhibited UVB-induced carcinogenesis, but this was not observed in mice fed a low-fat chow diet. Partial lipectomy in high-fat-fed mice decreased the number of keratoacanthomas and squamous cell carcinomas per mouse by 76 and 79%, respectively, compared with sham-operated control mice irradiated with UVB for 33 wk. Immunohistochemical analysis indicated that partial lipectomy increased caspase 3 (active form) positive cells by 48% in precancerous epidermis away from tumors, by 68% in keratoacanthomas, and by 224% in squamous cell carcinomas compared with sham-operated control mice. In addition, partial lipectomy decreased cell proliferation away from tumors and in tumors. RT-PCR analysis for adipokines revealed that mRNAs for TIMP1, MCP1, and SerpinE1 (proinflammatory/antiapoptotic cytokines) in the parametrial fat pads of sham-operated control mice were 54- to 83-fold higher than levels in compensatory fat that returned after surgery in partially lipectomized mice at the end of the tumor study. Feeding mice high-fat diets for 2 wk increased levels of TIMP1 and other adipokines in serum and epidermis, and these increases were inhibited by removal of the parametrial fat pads. Our results are a unique demonstration that surgical removal of a specific tissue fat results in inhibition of carcinogenesis in obese mice. This inhibition was associated with an increase in apoptosis and a decrease in proliferation in tumors and in precancerous areas away from tumors.
authors.affiliation: Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. sago@pharmacy.rutgers.edu
authors.forename: Yao-Ping
authors.initials: YP
authors.lastname: Lu
authors.forename: You-Rong
authors.initials: YR
authors.lastname: Lou
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Bernard
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Peng
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.forename: Paul
authors.initials: P
authors.lastname: Nghiem
authors.forename: Sue
authors.initials: S
authors.lastname: Shapses
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000601:surgery*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control* / Q000601:surgery; D053148:Caspase 3; D059305:Diet, High-Fat; D005260:Female; D007150:Immunohistochemistry; D007636:Keratoacanthoma / Q000517:prevention & control* / Q000601:surgery; D015187:Lipectomy / Q000379:methods*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D053148:Caspase 3; D001973:Bromodeoxyuridine