Abstract

Very few selected species of primates are known to be capable of entering torpor. This exciting discovery means that the ability to enter a natural state of dormancy is an ancestral trait among primates and, in phylogenetic terms, is very close to the human lineage. To explore the regulatory mechanisms that underlie primate torpor, we analyzed signal transduction cascades to discover those involved in coordinating tissue responses during torpor. The responses of mitogen-activated protein kinase (MAPK) family members to primate torpor were compared in six organs of control (aroused) versus torpid gray mouse lemurs, Microcebus murinus. The proteins examined include extracellular signal-regulated kinases (ERKs), c-jun NH2-terminal kinases (JNKs), MAPK kinase (MEK), and p38, in addition to stress-related proteins p53 and heat shock protein 27 (HSP27). The activation of specific MAPK signal transduction pathways may provide a mechanism to regulate the expression of torpor-responsive genes or the regulation of selected downstream cellular processes. In response to torpor, each MAPK subfamily responded differently during torpor and each showed organ-specific patterns of response. For example, skeletal muscle displayed elevated relative phosphorylation of ERK1/2 during torpor. Interestingly, adipose tissues showed the highest degree of MAPK activation. Brown adipose tissue displayed an activation of ERK1/2 and p38, whereas white adipose tissue showed activation of ERK1/2, p38, MEK, and JNK during torpor. Importantly, both adipose tissues possess specialized functions that are critical for torpor, with brown adipose required for non-shivering thermogenesis and white adipose utilized as the primary source of lipid fuel for torpor. Overall, these data indicate crucial roles of MAPKs in the regulation of primate organs during torpor.

Highlights

  • The ability to generate internal heat and maintain a high body temperature (Tb) has huge advantages for mammals, e.g., supporting advanced cognitive capabilities, speed and agility, and ability to live in cold climates [1]

  • The present study examined the protein expression and phosphorylated state of extracellular signalregulated kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK) kinase (MEK), c-jun NH2-terminal kinase (JNK), and p38, as well as the downstream targets heat shock protein 27 (HSP27) and p53, in different tissues of lemurs by comparing torpid animals with control aroused animals

  • Using custom multiplex panels, which were validated to crossreact in both primate and rodent species (Bio-Rad, Hercules, CA), relative changes in total and phosphoprotein expression of extracellular signal-regulated kinases (ERKs), MEK, JNK, p38, HSP27, and p53 were assessed in the skeletal muscle, heart, liver, kidney, brown adipose tissue (BAT), and white adipose tissue (WAT) by comparing control and torpid lemurs

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Summary

Introduction

The ability to generate internal heat and maintain a high body temperature (Tb) has huge advantages for mammals, e.g., supporting advanced cognitive capabilities, speed and agility, and ability to live in cold climates [1]. Many small mammals live ‘‘right on the edge’’ with the amount of food that they eat each day barely sufficient to keep them alive and warm until morning [2]. It is known that torpor occurs in a few species of primates – some lemurs that are native to Madagascar [2,6,7,8]. In phylogenetic terms, this indicates that the ability to enter torpor is an ancestral trait of the primate lineage, occurring among species that are very close to the human line [9]

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