Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal

Abstract

Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5-7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic-pituitary-thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism.

Keywords: lipid metabolism; reverse T3; seal; thyroxine; triiodothyronine.

Fig. 1.

Mean (±s.d.) mRNA expression levels of deiodinase type I (DI1) and type II (DI2) in (A,C) adipose and (B,D) muscle from fasting elephant seal pups. Asterisks denote significant (P<0.05) differences from week 1.

Fig. 2.

Mean (±s.d.) protein expression levels of deiodinase type I (DI1) and type II (DI2) in (A,C) adipose and (B,D) muscle from fasting elephant seal pups. Insets: representative western blots for each protein. Asterisks denote significant (P<0.05) differences from week 1.

Fig. 3.

Mean (±s.d.) mRNA expression levels of thyroid hormone receptor beta-1 (THrβ-1) in (A) adipose and (B) muscle, and mean (±s.e.m.) protein expression levels of THrβ-1 in (C) adipose and (D) muscle from fasting elephant seal pups. Insets: representative western blots for THrβ-1. Asterisks denote significant (P<0.05) differences from week 1.

Fig. 4.

Mean (±s.d.) mRNA expression levels of uncoupling protein-2 (UCP2) in (A) adipose and (B) muscle from fasted elephant seal pups. Asterisks denote significant (P<0.05) differences from week 1.