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The study explored the impact of overexpressing the enzyme spermidine/spermine N1-acetyltransferase (SSAT) in TRAMP mice, a model for prostate cancer. By cross-breeding these mice with SSAT-overexpressing mice, researchers observed a significant reduction in tumor growth, with genitourinary tract weights being 4 to 12 times less than in TRAMP mice alone by 30 to 36 weeks of age. This tumor suppression was attributed to increased polyamine catabolism, which depleted acetyl-CoA and S-adenosylmethionine, despite increased polyamine biosynthesis. Histopathological analysis showed less advanced tumors in TRAMP/SSAT mice, suggesting that SSAT overexpression could be a promising therapeutic strategy for prostate cancer. Additionally, a genitourinary disease index was developed to assess the treatment's impact, particularly in the C57BL/6 mouse background.

The study investigated the effects of genetically altered expression of spermidine/spermine N1-acetyltransferase (SSAT) on fat metabolism in mice, revealing that SSAT overexpression led to a lean phenotype with increased glucose and fatty acid oxidation, while SSAT knock-out mice showed increased body fat and reduced oxidation rates. These changes were linked to alterations in acetyl-CoA and malonyl-CoA levels, suggesting that SSAT modulated fat metabolism by influencing acetyl-CoA availability. The study involved more than 25 animals per group, providing robust data and highlighting a potential link between polyamine metabolism and obesity control.

Spermidine/spermine-N(1)-acetyltransferase (SSAT) was identified as a crucial enzyme regulating cellular polyamine content, impacting normal and neoplastic growth, ion channel regulation, and potentially cancer chemotherapy. SSAT activity was highly regulated and could be induced by various stimuli, affecting polyamine homeostasis and linking polyamine metabolism to lipid and carbohydrate metabolism. Increased SSAT activity led to a futile cycle consuming ATP and acetyl-CoA, and was associated with adverse effects such as pancreatic cell death, tissue growth blockage, behavioral changes, and hair loss. SSAT also interacted with proteins like hypoxia-inducible factor-1 alpha and NF-kappaB, though the exact mechanisms were unclear. While SSAT was considered a potential target for diseases beyond cancer, its broad physiological effects necessitated careful targeting to avoid toxicity.