Fasting increases the phosphorylation of AMPK and expression of sirtuin1 in muscle of adult male northern elephant seals ( Mirounga angustirostris )

Debby Lee,Rudy M Ortiz,Daniel E Crocker,Bridget Martinez

doi:10.14814/phy2.13114

Debby Lee, Rudy M Ortiz + Show 2 more

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https://doi.org/10.14814/phy2.13114

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Abstract

Fasting typically suppresses thyroid hormone (TH)‐mediated cellular events and increases sirtuin 1 (SIRT1) activity. THs may regulate metabolism through nongenomic pathways and directly through activation of adenosine monophosphate‐activated protein kinase (AMPK). Adult male elephant seals (Mirounga angustirostris) are active, hypermetabolic, and normothermic during their annual breeding fast, which is characterized by stable TH levels. However, the contribution of TH to maintenance of their fasting metabolism is unknown. To investigate the fasting effects on cellular TH‐mediated events and its potential association with SIRT1 and AMPK, we quantified plasma TH levels, mRNA expressions of muscle SIRT1 and TH‐associated genes as well as the phosphorylation of AMPK in adult, male northern elephant seals (n = 10/fasting period) over 8 weeks of fasting (early vs. late). Deiodinase type I (DI1) expression increased twofold with fasting duration suggesting that the potential for TH‐mediated cellular signaling is increased. AMPK phosphorylation increased 61 ± 21% with fasting suggesting that cellular metabolism is increased. The mRNA expression of the TH transporter, monocarboxylate transporter 10 (MCT10), increased 2.4‐fold and the TH receptor (THrβ‐1) decreased 30‐fold suggesting that cellular uptake of T4 is increased, but its subsequent cellular effects such as activation of AMPK are likely nongenomic. The up‐regulation of SIRT1 mRNA expression (2.6‐fold) likely contributes to the nongenomic activation of AMPK by TH, which may be necessary to maintain the expression of PGC‐1α. These coordinated changes likely contribute to the up‐regulation of mitochondrial metabolism to support the energetic demands associated with prolonged fasting in adult seals.

Highlights

Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
Adult male northern elephant seals (NES) exhibit relatively high metabolic rates despite their fasting state (Crocker et al 2012b). This would appear to be paradoxical, given that we have previously demonstrated that total T4 and T3 levels were unchanged with fasting duration in adult male NES (Crocker et al 2012b)
Metabolism via phosphorylation and activation of kinase pathways and proteins including muscle AMPK during fasting (Branvold et al 2008; Irrcher et al 2008). Given that these adult male NES are hypermetabolic (Crocker et al 2012b), all-the-while actively mating and fighting while simultaneously fasting, we suggest that the increase in free T3 (fT3) coupled with increased DI1 and monocarboxylate transporter 10 (MCT10) are necessary to support the nongenomic activation of AMPK

Summary

Introduction

Adult male northern elephant seals (NES) (M angustirostris) experience a 2–3 month period of prolonged food deprivation as part of their life history and have the highest sustained rates of fasting energy expenditure compared to other male pinnipeds (Crocker et al 2012b). During this fasting period, adult male NES are simultaneously competing for territory to establish access to estrus females and defending harems (Haley et al 1994; le Boeuf 1974), losing about 36% of their arrival body mass (Crocker et al 2012b; le Boeuf and Laws 1994). The factors contributing to the potential regulation of cellular metabolism during this energy-demanding fast remains largely underexplored

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