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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 explored how altering the expression of spermidine/spermine N1-acetyltransferase (SSAT) affected fat metabolism in mice. Transgenic mice overexpressing SSAT showed increased metabolic activity through the polyamine pathway, resulting in a leaner phenotype with reduced white adipose acetyl- and malonyl-CoA pools and enhanced glucose and palmitate oxidation. In contrast, SSAT knockout mice had decreased metabolic flux, increased body fat, and lower oxidation rates, especially on a high-fat diet. These results indicated that SSAT expression influenced acetyl- and malonyl-CoA levels, affecting fatty acid biosynthesis and oxidation, and thus body fat accumulation. The study underscored the role of SSAT in polyamine metabolism and its impact on fat metabolism via acetyl-CoA modulation.

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.