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Modulating liver cholesterol metabolism by 3-Iodothyronamine

Year 2017, Volume: 43 Issue: 2, 92 - 97, 15.06.2017

Nasrin Kazemıpour Neda Eskandarzade Sareh Hadıan Saeed Nazıfı

https://doi.org/10.16988/iuvfd.321791

Abstract

    In this study, we
attempt to find out whether chronic low dose 3-Iodothyronamine (an endogenous
metabolite of thyroid hormone) administration could modulate liver de novo
cholesterol synthesis, the same as thyroid hormones. Eighteen male mice were
divided randomly into treatment (n=10) and control (n=8) groups. The experimental
procedure was applied for 7 days during which test group received T1AM whereas
the control group received dimethyl sulfoxide and normal saline. The liver was
analyzed for HMG-CoA reductase concentration and hepatic lipase activity whiles
cholesterol, LDL and HDL concentrations were measured in the blood serum. There
was non-significant decrease in HMG-CoA reductase concentration (224±21.2
versus 187±32.5) in test group compared to control. Interestingly LDL and
cholesterol concentrations exhibited significant decrease in test group versus
the control. There was non-significant decrease in hepatic lipase activity
(771±316 versus 645±317) in test group versus the control. It appears that T1AM
reduced serum LDL and cholesterol just like T3, in contrast, it decreased
liver cholesterol biosynthesis contrary to THs.

Keywords

3-Iodothyronamine hepatic lipase HMG-CoA reductase

References

  • Angelin, B., Rudling, M., 2010. Lipid lowering with thyroid hormone and thyromimetics. Current Opinion in Lipidology 21, 499-506.
  • Bakker, O., Hudig, F., Meijssen, S., Wiersinga, W.M., 1998. Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene. Biochemical and Biophysical Research Communications 240, 517-521.
  • Beh, C.T., Cool, L., Phillips, J., Rine, J., 2001. Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157, 1117-1140.
  • Burtis, C.A., Ashwood, E.R., 1994. Tietz textbook of clinical chemistry, 2nd (Ed). Philadelphia, W.B. Saunders Company, pp.443-449.
  • Canaris, G.J., Manowitz, N.R., Mayor, G., Ridgway, C., 2000. The Colorado thyroid disease prevalence study. Archives of internal medicine 160, 526-534.
  • Cumero, S., Fogolari, F., Domenis, R., Zucchi, R., Mavelli, I., Contessi, S., 2012. Mitochondrial F0F1 -ATP synthase is a molecular target of 3-iodothyronamine, an endogenous metabolite of thyroid hormone. British Journal of Pharmacology 166, 2331-2347.
  • Gachon, F., Leuenberger, N., Claudel, T., Gos, P., Jouffe, C., Fleury Olela, F., de Mollerat du Jeu, X., Wahli, W., Schibler, U., 2011. Proline-and acidic amino acid-rich basic leucine zipper proteins modulate peroxisome proliferator-activated receptor α (PPARα) activity. Proceedings of the National Academy of Sciences USA 108, 4794-4799.
  • Gill, S., Chow, R., Brown, A.J., 2008. Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised. Progress in Lipid Research 47, 391-404.
  • Goldberg, I.J., Huang, L., Huggins, L.A., Yu, S., Nagareddy, P.R., Scanlan, T.S., Ehrenkranz, J.R., 2012. Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. Endocrinology 153, 5143-5149.
  • Istvan, E.S., Deisenhofer, J., 2001. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292, 1160-1164.
  • Karackattu, S.L., Trigatti, B., Krieger, M., 2006. Hepatic lipase deficiency delays atherosclerosis, myocardial infarction, and cardiac dysfunction and extends lifespan in SR-BI/apolipoprotein E double knockout mice. Arteriosclerosis, Thrombosis, and Vascular Biology 26, 548-54.
  • Kovanen, P.T., Nikkila, E.A., Miettinen, T.A., 1975. Regulation of cholesterol synthesis and storage in fat cells. The Journal of Lipid Research 16, 211-223.
  • Kussi, T., Sacrinen, P., Nikkila, E.A., 1980. Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein 2 in man. Atherosclerosis 36, 589-593.
  • Lagrost, L., 1994. Regulation of cholesteryl ester transfer protein (CETP) activity: Review of in vitro and in vivo studies. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 1215, 209-236.
  • Liggett, S.B., 2004. The two-timing thyroid. Nature Medicine 10, 582-583.
  • Lithell, H., Boberg, J., Hellsing, K., Ljunghall, S., Lundgvist, G., Vessby, B., Wide, L., 1981. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. European Journal of Clinical Investigation 11, 3-10.
  • Liu, Y.Y., Brent, G.A., 2010. Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends in Endocrinology and Metabolism 21, 166-173.
  • Lott, J.A., Patel, S.T., Sawhney, A.K., Kazmierczak, S.C., Love, J.E., 1986. Assays of serum lipase: analytical and clinical considerations. Clinical Chemistry 32, 1290-1302.
  • Mariotti, V., Melissari, E., Iofrida, C., Righi, M., DiRusso, M., Donzelli, R., Saba, A., Frascarelli, S., Chiellini, G., Zucchi, R., Pellegrini, S., 2014. Modulation of gene expression by 3-iodothyronamine: genetic evidence for a lipolytic pattern. PLoS ONE 9, 732-744.
  • Michaely, P., Li, W., Anderson, R., Cohen, J., Hobbs, H., 2004. The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits. The Journal of Biological Chemistry 279, 34023-34031.
  • Muls, E., Rossenen, M., Blaton, V., Lesaffre, E., Lamberigts, G., De Moor, P., 1984. Serum lipids and apolipoproteins AI, AII and B in primary hypothyroidism before and during treatment. European Journal of Clinical Investigation 14, 12-15.
  • Ness, G.C., Dugan, R.E., Lakshmanan, M.R., Nepokroeff, C.M., Porter, J.W., 1973. Stimulation of hepatic β-hydroxy-β-methylglutaryl Coenzyme A reductase in hypophysectomized rats by L-triiodothyronine. Proceedings of the National Academy of Sciences of the USA 70, 3839-3842.
  • O’Brien, T., Dinneen, S.F., O’Brien, P.C., Palumbo, P.J., 1990. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clinic Endocrinology 68, 860-866.
  • Olivier, L.M., Krisans, S.K., 2000. Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1529, 89-102.
  • Regard, J.B., Kataoka, H., Cano, D.A., Camerer, E., Yin, L., Zheng, Y.W., Scanlan, T.S., Hebrok, M., Coughlin, S.R., 2007. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. Journal of Clinical Investigation 117, 4034-4043.
  • Santamarina-Fojo, S., Haudenschild, C., Amar, M., 1998. The role of hepatic lipase in lipoprotein metabolism and atherosclerosis. Current Opinion in Lipidology 9, 211-219.
  • Scanlan, T.S., Suchland, K.L., Hart, M.E., Chiellini, G., Huang, Y., Kruzich, P.J., Frascarelli, S., Crossley, D.A., Bunzow, J.R., Ronca-Testoni, S., Lin, E.T., Hatton, D., Zucchi, R., Grandy, D.K., 2004. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nature Medicine 10, 638-642.
  • Senese, R., Cioffi, F., de Lange, P., Goglia, F., Lanni, A., 2014. Thyroid: biological actions of ‘nonclassical’ thyroid hormones. Journal of Endocrinology 221, R1-R12.
  • Shin, D.J., Osborne, T.F., 2003. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element- Binding Protein-2 (SREBP-2). The Journal of Biological Chemistry 278, 34114-34118.
  • Sirinian, M.I., Belleudi, F., Campagna, F., Ceridono, M., Garofalo, T., Quagliarini, F., Verna, R., Calandra, S., Bertolini, S., Sorice, M., Torrisi, M.R., Arca, M., 2005. Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes. The Journal of Biological Chemistry 280, 38416-38423.
  • Snead, A.N., Santos, M.S., Seal, R.P., Miyakawa, M., Edwards, R.H., Scanlan, T.S., 2007. Thyronamines inhibit plasma membrane and vesicular monoamine transport. ACS Chemical Biology 2, 390-398.
  • Venditti, P., Napolitano, G., Di Stefano, L, Chiellini, G., Zucchi, R., Scanlan, T.S., Di Meo, S., 2011. Effects of the thyroid hormone derivatives 3-iodothyronamine and thyronamine on rat liver oxidative capacity. Molecular and Cellular Endocrinology 341, 55-62.
  • Weatherman, R.V., 2007. A triple play for thyroid hormone. ACS Chemical Biology 2, 377-379.
  • Zambon, A., Deeb, S.S., Pauletto, P., Crepaldi, G., Brunzell, J.D., 2003. Hepatic lipase: a marker for cardiovascular disease risk and response to therapy. Current Opinion in Lipidology 14, 179-189.
  • Zucchi, R., Ghelardoni, S., Chiellini, G., 2010. Cardiac effects of thyronamines. Heart Failure Reviews 15, 171-176.

Modulating liver cholesterol metabolism by 3-Iodothyronamine

Year 2017, Volume: 43 Issue: 2, 92 - 97, 15.06.2017

Nasrin Kazemıpour Neda Eskandarzade Sareh Hadıan Saeed Nazıfı

https://doi.org/10.16988/iuvfd.321791

Abstract

    In this study, we
attempt to find out whether chronic low dose 3-Iodothyronamine (an endogenous
metabolite of thyroid hormone) administration could modulate liver de novo
cholesterol synthesis, the same as thyroid hormones. Eighteen male mice were
divided randomly into treatment (n=10) and control (n=8) groups. The experimental
procedure was applied for 7 days during which test group received T1AM whereas
the control group received dimethyl sulfoxide and normal saline. The liver was
analyzed for HMG-CoA reductase concentration and hepatic lipase activity whiles
cholesterol, LDL and HDL concentrations were measured in the blood serum. There
was non-significant decrease in HMG-CoA reductase concentration (224±21.2
versus 187±32.5) in test group compared to control. Interestingly LDL and
cholesterol concentrations exhibited significant decrease in test group versus
the control. There was non-significant decrease in hepatic lipase activity
(771±316 versus 645±317) in test group versus the control. It appears that T1AM
reduced serum LDL and cholesterol just like T3, in contrast, it decreased
liver cholesterol biosynthesis contrary to THs.

Keywords

3-Iodothyronamine hepatic lipase HMG-CoA reductase

References

  • Angelin, B., Rudling, M., 2010. Lipid lowering with thyroid hormone and thyromimetics. Current Opinion in Lipidology 21, 499-506.
  • Bakker, O., Hudig, F., Meijssen, S., Wiersinga, W.M., 1998. Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene. Biochemical and Biophysical Research Communications 240, 517-521.
  • Beh, C.T., Cool, L., Phillips, J., Rine, J., 2001. Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157, 1117-1140.
  • Burtis, C.A., Ashwood, E.R., 1994. Tietz textbook of clinical chemistry, 2nd (Ed). Philadelphia, W.B. Saunders Company, pp.443-449.
  • Canaris, G.J., Manowitz, N.R., Mayor, G., Ridgway, C., 2000. The Colorado thyroid disease prevalence study. Archives of internal medicine 160, 526-534.
  • Cumero, S., Fogolari, F., Domenis, R., Zucchi, R., Mavelli, I., Contessi, S., 2012. Mitochondrial F0F1 -ATP synthase is a molecular target of 3-iodothyronamine, an endogenous metabolite of thyroid hormone. British Journal of Pharmacology 166, 2331-2347.
  • Gachon, F., Leuenberger, N., Claudel, T., Gos, P., Jouffe, C., Fleury Olela, F., de Mollerat du Jeu, X., Wahli, W., Schibler, U., 2011. Proline-and acidic amino acid-rich basic leucine zipper proteins modulate peroxisome proliferator-activated receptor α (PPARα) activity. Proceedings of the National Academy of Sciences USA 108, 4794-4799.
  • Gill, S., Chow, R., Brown, A.J., 2008. Sterol regulators of cholesterol homeostasis and beyond: the oxysterol hypothesis revisited and revised. Progress in Lipid Research 47, 391-404.
  • Goldberg, I.J., Huang, L., Huggins, L.A., Yu, S., Nagareddy, P.R., Scanlan, T.S., Ehrenkranz, J.R., 2012. Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway. Endocrinology 153, 5143-5149.
  • Istvan, E.S., Deisenhofer, J., 2001. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292, 1160-1164.
  • Karackattu, S.L., Trigatti, B., Krieger, M., 2006. Hepatic lipase deficiency delays atherosclerosis, myocardial infarction, and cardiac dysfunction and extends lifespan in SR-BI/apolipoprotein E double knockout mice. Arteriosclerosis, Thrombosis, and Vascular Biology 26, 548-54.
  • Kovanen, P.T., Nikkila, E.A., Miettinen, T.A., 1975. Regulation of cholesterol synthesis and storage in fat cells. The Journal of Lipid Research 16, 211-223.
  • Kussi, T., Sacrinen, P., Nikkila, E.A., 1980. Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein 2 in man. Atherosclerosis 36, 589-593.
  • Lagrost, L., 1994. Regulation of cholesteryl ester transfer protein (CETP) activity: Review of in vitro and in vivo studies. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 1215, 209-236.
  • Liggett, S.B., 2004. The two-timing thyroid. Nature Medicine 10, 582-583.
  • Lithell, H., Boberg, J., Hellsing, K., Ljunghall, S., Lundgvist, G., Vessby, B., Wide, L., 1981. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. European Journal of Clinical Investigation 11, 3-10.
  • Liu, Y.Y., Brent, G.A., 2010. Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends in Endocrinology and Metabolism 21, 166-173.
  • Lott, J.A., Patel, S.T., Sawhney, A.K., Kazmierczak, S.C., Love, J.E., 1986. Assays of serum lipase: analytical and clinical considerations. Clinical Chemistry 32, 1290-1302.
  • Mariotti, V., Melissari, E., Iofrida, C., Righi, M., DiRusso, M., Donzelli, R., Saba, A., Frascarelli, S., Chiellini, G., Zucchi, R., Pellegrini, S., 2014. Modulation of gene expression by 3-iodothyronamine: genetic evidence for a lipolytic pattern. PLoS ONE 9, 732-744.
  • Michaely, P., Li, W., Anderson, R., Cohen, J., Hobbs, H., 2004. The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits. The Journal of Biological Chemistry 279, 34023-34031.
  • Muls, E., Rossenen, M., Blaton, V., Lesaffre, E., Lamberigts, G., De Moor, P., 1984. Serum lipids and apolipoproteins AI, AII and B in primary hypothyroidism before and during treatment. European Journal of Clinical Investigation 14, 12-15.
  • Ness, G.C., Dugan, R.E., Lakshmanan, M.R., Nepokroeff, C.M., Porter, J.W., 1973. Stimulation of hepatic β-hydroxy-β-methylglutaryl Coenzyme A reductase in hypophysectomized rats by L-triiodothyronine. Proceedings of the National Academy of Sciences of the USA 70, 3839-3842.
  • O’Brien, T., Dinneen, S.F., O’Brien, P.C., Palumbo, P.J., 1990. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clinic Endocrinology 68, 860-866.
  • Olivier, L.M., Krisans, S.K., 2000. Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1529, 89-102.
  • Regard, J.B., Kataoka, H., Cano, D.A., Camerer, E., Yin, L., Zheng, Y.W., Scanlan, T.S., Hebrok, M., Coughlin, S.R., 2007. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. Journal of Clinical Investigation 117, 4034-4043.
  • Santamarina-Fojo, S., Haudenschild, C., Amar, M., 1998. The role of hepatic lipase in lipoprotein metabolism and atherosclerosis. Current Opinion in Lipidology 9, 211-219.
  • Scanlan, T.S., Suchland, K.L., Hart, M.E., Chiellini, G., Huang, Y., Kruzich, P.J., Frascarelli, S., Crossley, D.A., Bunzow, J.R., Ronca-Testoni, S., Lin, E.T., Hatton, D., Zucchi, R., Grandy, D.K., 2004. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nature Medicine 10, 638-642.
  • Senese, R., Cioffi, F., de Lange, P., Goglia, F., Lanni, A., 2014. Thyroid: biological actions of ‘nonclassical’ thyroid hormones. Journal of Endocrinology 221, R1-R12.
  • Shin, D.J., Osborne, T.F., 2003. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element- Binding Protein-2 (SREBP-2). The Journal of Biological Chemistry 278, 34114-34118.
  • Sirinian, M.I., Belleudi, F., Campagna, F., Ceridono, M., Garofalo, T., Quagliarini, F., Verna, R., Calandra, S., Bertolini, S., Sorice, M., Torrisi, M.R., Arca, M., 2005. Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes. The Journal of Biological Chemistry 280, 38416-38423.
  • Snead, A.N., Santos, M.S., Seal, R.P., Miyakawa, M., Edwards, R.H., Scanlan, T.S., 2007. Thyronamines inhibit plasma membrane and vesicular monoamine transport. ACS Chemical Biology 2, 390-398.
  • Venditti, P., Napolitano, G., Di Stefano, L, Chiellini, G., Zucchi, R., Scanlan, T.S., Di Meo, S., 2011. Effects of the thyroid hormone derivatives 3-iodothyronamine and thyronamine on rat liver oxidative capacity. Molecular and Cellular Endocrinology 341, 55-62.
  • Weatherman, R.V., 2007. A triple play for thyroid hormone. ACS Chemical Biology 2, 377-379.
  • Zambon, A., Deeb, S.S., Pauletto, P., Crepaldi, G., Brunzell, J.D., 2003. Hepatic lipase: a marker for cardiovascular disease risk and response to therapy. Current Opinion in Lipidology 14, 179-189.
  • Zucchi, R., Ghelardoni, S., Chiellini, G., 2010. Cardiac effects of thyronamines. Heart Failure Reviews 15, 171-176.
There are 35 citations in total.

Details

Subjects Health Care Administration
Journal Section Research Article
Authors

Nasrin Kazemıpour This is me

Neda Eskandarzade This is me

Sareh Hadıan This is me

Saeed Nazıfı

Publication Date June 15, 2017
Published in Issue Year 2017 Volume: 43 Issue: 2

Cite

APA Kazemıpour, N., Eskandarzade, N., Hadıan, S., Nazıfı, S. (2017). Modulating liver cholesterol metabolism by 3-Iodothyronamine. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, 43(2), 92-97. https://doi.org/10.16988/iuvfd.321791
AMA Kazemıpour N, Eskandarzade N, Hadıan S, Nazıfı S. Modulating liver cholesterol metabolism by 3-Iodothyronamine. iuvfd. July 2017;43(2):92-97. doi:10.16988/iuvfd.321791
Chicago Kazemıpour, Nasrin, Neda Eskandarzade, Sareh Hadıan, and Saeed Nazıfı. “Modulating Liver Cholesterol Metabolism by 3-Iodothyronamine”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 43, no. 2 (July 2017): 92-97. https://doi.org/10.16988/iuvfd.321791.
EndNote Kazemıpour N, Eskandarzade N, Hadıan S, Nazıfı S (July 1, 2017) Modulating liver cholesterol metabolism by 3-Iodothyronamine. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 43 2 92–97.
IEEE N. Kazemıpour, N. Eskandarzade, S. Hadıan, and S. Nazıfı, “Modulating liver cholesterol metabolism by 3-Iodothyronamine”, iuvfd, vol. 43, no. 2, pp. 92–97, 2017, doi: 10.16988/iuvfd.321791.
ISNAD Kazemıpour, Nasrin et al. “Modulating Liver Cholesterol Metabolism by 3-Iodothyronamine”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 43/2 (July 2017), 92-97. https://doi.org/10.16988/iuvfd.321791.
JAMA Kazemıpour N, Eskandarzade N, Hadıan S, Nazıfı S. Modulating liver cholesterol metabolism by 3-Iodothyronamine. iuvfd. 2017;43:92–97.
MLA Kazemıpour, Nasrin et al. “Modulating Liver Cholesterol Metabolism by 3-Iodothyronamine”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, vol. 43, no. 2, 2017, pp. 92-97, doi:10.16988/iuvfd.321791.
Vancouver Kazemıpour N, Eskandarzade N, Hadıan S, Nazıfı S. Modulating liver cholesterol metabolism by 3-Iodothyronamine. iuvfd. 2017;43(2):92-7.