The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms†

Abstract

Torpor and hibernation are powerful strategies enabling animals to survive periods of low resource availability. The state of torpor results from an active and drastic reduction of an individual’s metabolic rate (MR) associated with a relatively pronounced decrease in body temperature. To date, several forms of torpor have been described in all three mammalian subclasses, i.e., monotremes, marsupials, and placentals, as well as in a few avian orders. This review highlights some of the characteristics, from the whole organism down to cellular and molecular aspects, associated with the torpor phenotype. The first part of this review focuses on the specific metabolic adaptations of torpor, as it is used by many species from temperate zones. This notably includes the endocrine changes involved in fat- and food-storing hibernating species, explaining biomedical implications of MR depression. We further compare adaptive mechanisms occurring in opportunistic vs. seasonal heterotherms, such as tropical and sub-tropical species. Such comparisons bring new insights into the metabolic origins of hibernation among tropical species, including resistance mechanisms to oxidative stress. The second section of this review emphasizes the mechanisms enabling heterotherms to protect their key organs against potential threats, such as reactive oxygen species, associated with the torpid state. We notably address the mechanisms of cellular rehabilitation and protection during torpor and hibernation, with an emphasis on the brain, a central organ requiring protection during torpor and recovery. Also, a special focus is given to the role of an ubiquitous and readily-diffusing molecule, hydrogen sulfide (H2S), in protecting against ischemia-reperfusion damage in various organs over the torpor-arousal cycle and during the torpid state. We conclude that (i) the flexibility of torpor use as an adaptive strategy enables different heterothermic species to substantially suppress their energy needs during periods of severely reduced food availability, (ii) the torpor phenotype implies marked metabolic adaptations from the whole organism down to cellular and molecular levels, and (iii) the torpid state is associated with highly efficient rehabilitation and protective mechanisms ensuring the continuity of proper bodily functions. Comparison of mechanisms in monotremes and marsupials is warranted for understanding the origin and evolution of mammalian torpor.

Heterothermy as the Norm, Homeothermy as the Exception: Variable Torpor Patterns in the South American Marsupial Monito del Monte (Dromiciops gliroides)

“…On the other hand, monitos exhibited a torpid T B that was almost indistinguishable from T A (Figure 3), with an extreme of 4.13°C in the outdoor experiment and 0.08°C in the climatic chamber (Figure 5), where animals endured sub-freezing temperatures (Figure 8). These minimum torpid T B are considerably lower than what is observed in hibernators such as the garden dormouse (=6°C, from Table 1 in Giroud et al, 2021) and lower than what is reported for most Holarctic and non-Holarctic heterotherms (see Figure 3 in Nowack et al, 2020). Similarly, torpor bout duration reached a maximum of 5.2 days (125 h, Figure 3), which is coincident with the first report of Bozinovic et al (2004) in the laboratory (=5.0 days).…”

“…This dependence is mechanistically associated with a hypothalamic neuronal circuit stimulated by fasting that lowers the set point for T B control, a phenomenon known for decades ( Heller and Colliver, 1974 ; Geiser et al, 1990 ), and recently confirmed at the molecular level in laboratory mice ( Hrvatin et al, 2020 ; Takahashi et al, 2020 ). In the case of D. gliroides , animals can sense the presence of food in the environment and adjust their energy expenditure (by torpor) on a weekly basis ( Giroud et al, 2021 ; Nespolo et al, 2021 ). This modulation also occurs in other mammalian species of the southern hemisphere, such as African elephant shrews, which show daily heterothermy modulated by food, T A , and photoperiod ( Mzilikazi and Lovegrove, 2004 ); in the short-beaked echidnas, which can shift from short torpor to hibernation depending on habitat conditions ( Nicol and Andersen, 2007 ); in the marsupial Antechinus , which intensify torpor use under environmental threats such as food scarcity and fires ( Stawski et al, 2016 ); and in spiny mice, which react with heterothermy in response to storms of floods (reviewed in Nowack et al, 2020 ).…”

MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease?

“…), miRNA responses, suppressing mTOR signaling and other pathways ( Figure 3 and Table 1 ). All these suggest that an ancient “switch” could be hidden in the human genome that could trigger torpor in humans or be induced to extend donor organ preservation times [ 135 , 136 , 137 ]. Indeed, miRNA plays an important role during the transitions between active vs torpid states in multiple animal models [ 2 , 71 , 138 ].…”

Dynamic Function and Composition Shift in Circulating Innate Immune Cells in Hibernating Garden Dormice

“…the linked ROS production (Muzaffar et al, 2008a,b;Al-Magableh et al, 2014; also see for review Giroud et al, 2020). Talaei et al (2012) report endogenous production of H 2 S in hibernating Syrian hamsters (Mesocricetus auratus), with increased levels during early and late torpor and a normalization, i.e., low levels, during interbout arousal.…”