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: Yao-Ping Lu, You-Rong Lou, Jamie J Bernard, Qing-Yun Peng, Tao Li, Yong Lin, Weichung Joe Shih, Paul Nghiem, Sue Shapses, George C Wagner, Allan H Conney
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 23 Pg. 9065-70 (Jun 05 2012) ISSN: 1091-6490 [Electronic] United States
• PMID: 22615388 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Caspase 3
• Bromodeoxyuridine

Topics

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