|Simmen, Frank -|
|Mercado, Charles -|
|Zavacki, Ann Marie -|
|Huang, Stephen -|
|Greenway, Amy -|
|Kang, Ping -|
|Bowman, Margaret -|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 21, 2009
Publication Date: November 15, 2010
Citation: Simmen, F.A., Mercado, C.P., Zavacki, A., Huang, S.A., Greenway, A.D., Kang, P., Bowman, M.T., Prior, R.L. 2010. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat. Journal of Nutritional Biochemistry. 21(11):1106-1113. Interpretive Summary: We determined effects of feeding a soy protein isolate and separately, the soy compound genistein on fat metabolism and the thyroid hormone system in male rats. Soy protein diet reduced body fat deposition as well as accumulation of fat in the liver. We also found that a special class of enzymes that are involved with thyroid hormone metabolism were affected by dietary genistein and soy protein to positively impact liver metabolic function, with ramifications for prevention of multiple chronic diseases that are characterized by excessive lipid accumulation in the liver.
Technical Abstract: We determined effects of soy protein (SPI) and the isoflavone genistein (GEN) on mRNA expression of key lipid metabolism and thyroid hormone system genes in young adult, male Sprague-Dawley rats. SPI-fed rats had less retroperitoneal fat and less hepato-steatosis than casein (CAS, control protein)- or GEN-fed rats. Hepatic PPARa (Ppara) and Carnitine Palmitoyltransferase Ia (Cpt1a) transcripts were (or tended to be) elevated with SPI but not GEN diet. Hepatic pyruvate dehydrogenase kinase-4 (Pdk4), acyl-CoA thioesterase 2 (Acot2), and cytochrome P450 4A10 (Cyp4a10) mRNA abundance was (or tended to be) reduced with SPI; SPI effects on Acot2 and Cyp4a10 were recapitulated with GEN. SPI (but not GEN) suppressed duodenal Pdk4 and 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) mRNA abundance. Liver iodothyronine deiodinase types 1 and 2 (Dio1 and Dio2) mRNA levels were increased with SPI; the effect on liver Dio2 RNA, but not Dio1 mRNA, also was observed with GEN. Both SPI and GEN increased amount and/or activity of hepatic types 1 and 2 deiodinases (D1 and D2); whereas, diet had no effect on D1 and type 3 deiodinase (D3) activities in small intestine (this tissue had no detectable D2 activity). Tissue-specific effects of SPI and GEN on lipid catabolic and thyroid hormone system gene expression may contribute to reductions in hepato-steatosis and peripheral fat deposition. Regulation of iodothyronine deiodinase synthesis by genistein and soy protein constitutes newly recognized aspects of nutritional bio-active factor regulation of liver metabolic function, with ramifications for multiple chronic diseases characterized by excessive lipid accumulation in the liver.