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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet.

Authors: Lu, Yao-Ping; Lou, You-Rong; Bernard, Jamie J; Peng, Qing-Yun; Li, Tao; Lin, Yong; Shih, Weichung Joe; Nghiem, Paul; Shapses, Sue; Wagner, George C; Conney, Allan H

Published In Proc Natl Acad Sci U S A, (2012 Jun 05)

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.

PubMed ID: 22615388 Exiting the NIEHS site

MeSH Terms: Absorptiometry, Photon; Adipose Tissue/surgery*; Animals; Apoptosis/physiology*; Bromodeoxyuridine; Carcinoma, Squamous Cell/prevention & control*; Carcinoma, Squamous Cell/surgery; Caspase 3; Diet, High-Fat; Female; Immunohistochemistry; Keratoacanthoma/prevention & control*; Keratoacanthoma/surgery; Lipectomy/methods*; Mice; Neoplasms, Radiation-Induced/prevention & control*; Neoplasms, Radiation-Induced/surgery; Reverse Transcriptase Polymerase Chain Reaction; Ultraviolet Rays*

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