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

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.

Expression of obesity-related adipokine genes during fasting in a naturally obese marine mammal

“…It has been suggested that NAMPT regulates adiponectin expression via the activity of NAD ϩ -dependent SIRT1 (47). NAMPT and ADIPOQ expression were also correlated in this study, and SIRT1 upregulation has been reported during fasting in elephant seals, as mentioned above (24). However, the insulinsensitizing effects of NAMPT observed in humans and rodents contrasts with the state of insulin resistance observed in fasting seals, and its biological function in this fasting-adapted species warrants further investigation.…”

Repeated adrenocorticotropic hormone administration alters adrenal and thyroid hormones in free-ranging elephant seals

“…For example, mean thyroid hormone levels do not change in male northern elephant seals over their extended breeding fast, enabling them to maintain elevated metabolic rates for its duration. Furthermore, the ability of individual seals to elevate T3 is associated with higher daily energy expenditure and breeding success ( Crocker et al , 2012 ; Lee et al , 2017 ). Metabolic suppression, even for short periods during this life-history stage, could lead to an inability to sustain reproductive behaviour and decrease fitness.…”

Ketogenic Diet and Skeletal Muscle Hypertrophy: a Frenemy Relationship?

“…AMPK phosphorylation blunts Akt/mTOR pathways. But, although it has been demonstrated that fasting induces muscle AMPK activation in animals’ models (Lee et al, 2017), in humans available data do not confirm these results; indeed, fasting in humans seems to reduce activation of Akt pathways without affecting AMPK (Wijngaarden et al, 2014). Regarding the effects of KD on these pathways, Kennedy and colleagues (2007) demonstrated a threefold increase in AMPK activity in the soleus muscle of rats fed with KD, but no relevant data are available in humans.…”