Differential Role of Hypothalamic AMPKα Isoforms in Fish: an Evolutive Perspective

Abstract

In mammals, hypothalamic AMP-activated protein kinase (AMPK) α1 and α2 isoforms mainly relate to regulation of thermogenesis/liver metabolism and food intake, respectively. Since both isoforms are present in fish, which do not thermoregulate, we assessed their role(s) in hypothalamus regarding control of food intake and energy homeostasis. Since many fish species are carnivorous and mostly mammals are omnivorous, assessing if the role of hypothalamic AMPK is different is also an open question. Using the rainbow trout as a fish model, we first observed that food deprivation for 5 days did not significantly increase phosphorylation status of AMPKα in hypothalamus. Then, we administered adenoviral vectors that express dominant negative (DN) AMPKα1 or AMPKα2 isoforms. The inhibition of AMPKα2 (but not AMPKα1) led to decreased food intake. The central inhibition of AMPKα2 resulted in liver with decreased capacity of use and synthesis of glucose, lipids, and amino acids suggesting that a signal of nutrient abundance flows from hypothalamus to the liver, thus suggesting a role for central AMPKα2 in the regulation of peripheral metabolism in fishes. The central inhibition of AMPKα1 induced comparable changes in liver metabolism though at a lower extent. From an evolutionary point of view, it is of interest that the function of central AMPKα2 remained similar throughout the vertebrate lineage. In contrast, the function of central AMPKα1 in fish relates to modulation of liver metabolism whereas in mammals modulates not only liver metabolism but also brown adipose tissue and thermogenesis.

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Funding

This study was supported by research grants from Spanish Agencia Estatal de Investigación (AEI) and European Fund of Regional Development (FEDER) to JLS (AGL2016-74857-C3-1-R) and ML (SAF2015-71026-R). M.C-S was recipient of a postdoctoral fellowship (Program Juan de la Cierva-Incorporación) from AEI (IJCI-2016-30499). S.C. was recipient of a predoctoral fellowship (Program FPU) from Spanish Ministerio de Educación, Cultura y Deporte (FPU16/00045).

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ML and JLS conceived the experiments. MC-S, SC, and CV conducted the experiments and carried out the assessment of mRNA abundance, enzyme activities, and metabolite levels. RA-O carried out the histochemical procedures. V.C and LL-P carried out Western blots. MC-S, VC, ML, and JLS analyzed the results. MC-S, ML, and JLS wrote the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to José L. Soengas.

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The authors declare that they have no conflicts of interest.

Ethical Approval

The experiments described comply with the Guidelines of the European Union Council (2010/63/UE) and of the Spanish Government (RD53/2013) for the use of animals in research and were approved by the Ethics Committee of the Universidade de Vigo.

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Conde-Sieira, M., Capelli, V., Álvarez-Otero, R. et al. Differential Role of Hypothalamic AMPKα Isoforms in Fish: an Evolutive Perspective. Mol Neurobiol 56, 5051–5066 (2019). https://doi.org/10.1007/s12035-018-1434-9

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Keywords

  • Trout
  • Hypothalamus
  • AMPK isoforms
  • Food intake
  • Hepatic metabolism