Abstract
Metformin has been proposed as a potential drug treatment to reduce liver steatosis. Therefore, the study of the effects of in vivo metformin administration, on hepatic fat metabolism in the isolated perfused liver is of great interest. We have studied the effects of in vivo metformin treatment of rats with experimentally induced overweight, hyperglycemia and hypertriglyceridemia, on plasma hormone and metabolite concentrations, as well as on triglyceride and ketone body output by the isolated perfused livers. Sprague–Dawley rats were fed ad libitum with a high lipid diet for 10 weeks. Then, one rat group was treated for 7 days with 350 μg/kg of BW of metformin per day, whereas the control group received only water. Thereafter, the livers were excised and perfused in vitro under controlled conditions. The hypertriglyceridemic rats had a greater body weight, as well as greater plasma glucose, insulin and triglyceride concentrations, than the control rats fed ordinary chow. In vivo metformin treatment decreased plasma glucose, insulin and triglyceride concentrations. With respect to the overweight, hyperglycemic, hypertriglyceridemic, untreated control rats, the cumulative (i.e. over 3 h of perfusion) triglyceride output by the perfused livers was decreased by >60%, whereas total ketone body (i.e. the sum of 3-hydroxybutyrate and acetoacetate) output was increased by >100% (p < 0.01 for both). In conclusion, the in vivo treatment with metformin of rats with diet-induced overweight and hypertriglyceridemia is capable to re-address hepatic fatty acid metabolism from lipogenesis toward fat oxidation and ketone body production, either directly or through a reduction of insulin concentrations.
Similar content being viewed by others
Notes
These data have been briefly included in concise form in the review articles: “Glucagon and lipid disorders”, by A. Tiengo, R. Nosadini, A. Meneghel, P. Tessari, S. Del Prato, D. Fedele, G. Crepaldi, published in: Current Views on Hypoglicemia and Glucagon. Ed. by D. Andreani, P.J. Lefebvre, V. Marks. Academic Press 1980, pp. 151–161, and in “Hormonal effects of hypolipemic agents” by A. Tiengo, P. Tessari, R. Nosadini, S. Del Prato, D. Fedele, G. Crepaldi, published in: Drug Affecting Lipid Metabolism, Ed. By R. Fumagalli, D. Kritchevsky and R. Paoletti, Elsevier North Holland Biomedical Press 1980, pp 321–330.
References
Angulo P (2002) Non-alcoholic fatty liver disease. N Engl J Med 346:1221–1231
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M (2003) Non-alcoholic fatty liver, steatohepatitis and the metabolic sindrome. Hepatology 37:917–923
Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G (2005) Randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100(5):1082–1090
Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM (2000) Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 6:998–1003
Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152
Nosadini R, Ursini F, Tessari P, De Biasi F, Tiengo A (1979) Hormonal and metabolic characteristics of genetically obese and dietary obese Sprague–Dawley rats. Eur J Clin Invest 10:113–118
Miller LL (1973) Technique of isolated rat liver perfusion. In: Bartosek I, Guaitani A, Miller LL (eds) Isolated liver perfusion and its application. Raven Press, New York, pp 11–53
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tessari, P., Tiengo, A. Metformin treatment of rats with diet-induced overweight and hypertriglyceridemia decreases plasma triglyceride concentrations, while decreasing triglyceride and increasing ketone body output by the isolated perfused liver. Acta Diabetol 45, 143–145 (2008). https://doi.org/10.1007/s00592-008-0032-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-008-0032-0