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Title: Metformin counteracts glucose-dependent lipogenesis and impairs transdeamination in the liver of gilthead sea bream (Sparus aurata)
Author: Rashidpour, Ania
Silva-Marrero, Jonás I.
Seguí, Lidia
Baanante, Isabel V.
Metón Teijeiro, Isidoro
Keywords: Metabolisme dels glúcids
Carbohydrate metabolism
Sparus aurata
Hypoglucemic agents
Issue Date: 2019
Publisher: American Physiological Society
Abstract: Metformin is an anti-diabetic drug with a major impact on regulating blood glucose levels by decreasing hepatic gluconeogenesis but also affecting other pathways, including glucose transport and energy/lipid metabolism. Carnivorous fish are considered glucose intolerant, as they exhibit poor ability to using dietary carbohydrates. To increase the current knowledge about the molecular mechanisms by which metformin can improve glucose homeostasis in carnivorous fish, we addressed the effect of intraperitoneal administration of metformin, in the presence or absence of a glucose load, on metabolic rate-limiting enzymes and lipogenic factors in the liver of gilthead sea bream (Sparus aurata). Hyperglycemia markedly up-regulated the expression of glycolytic enzymes (glucokinase and 6-phosphofructo-1-kinase, PFK1) 5 h following glucose administration, while at 24 h post-treatment it increased isocitrate dehydrogenase (IDH) activity, a key enzyme of the tricarboxylic acid cycle, and the expression of lipogenic factors (PGC1b, Lpin1 and SREBP1). Metformin counteracted glucose-dependent effects, and down-regulated glutamate dehydrogenase, alanine aminotransferase and mTOR 5 h post-treatment in the absence of a glucose load, leading to decreased long-term activity of PFK1 and IDH. The results of the present study suggest that hyperglycemia enhances lipogenesis in the liver of S. aurata, and that metformin may exert specific metabolic effects in fish by decreasing hepatic transdeamination and supressing the use of amino acids as gluconeogenic substrates. Our findings highlight the role of amino acid metabolism in the glucose-intolerant carnivorous fish model. KEYWORDS: Glutamate dehydrogenase; Lipogenesis; Liver; Metformin; Sparus aurata
Note: Versió postprint del document publicat a:
It is part of: American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 2019, vol. In press
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ISSN: 0363-6119
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

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