Ambient temperature‐mediated changes in hepatic gene expression of a mammalian herbivore (Neotoma lepida)

Abstract

Herbivores regularly ingest natural toxins produced by plants as a defence against herbivory. Recent work suggests that compound toxicity is exacerbated at higher ambient temperatures. This phenomenon, known as temperature-dependent toxicity (TDT), is the likely result of decreased liver function at warmer temperatures; however, the underlying cause of TDT remains speculative. In the present study, we compared the effects of temperature and dietary plant toxins on differential gene expression in the liver of an herbivorous rodent (Neotoma lepida), using species-specific microarrays. Expression profiles revealed a greater number of differentially expressed genes at an ambient temperature below the thermal neutral zone for N. lepida (22°C) compared to one within (27°C). Genes and pathways upregulated at 22°C were related to growth and biosynthesis, whereas those upregulated at 27°C were associated with gluconeogenesis, apoptosis and protein misfolding, suggestive of a stressed state for the liver. Additionally, few genes associated with xenobiotic metabolism were induced when woodrats ingested plant toxins compared to nontoxic diets, regardless of temperature. Taken together, the results highlight the important role of ambient temperature on gene expression profiles in the desert woodrat. Temperatures just below the thermal neutral zone might be a favourable state for liver metabolism. Furthermore, the reduction in the number of genes expressed at a temperature within the thermal neutral zone indicates that liver function may be reduced at temperatures that are not typically considered as thermally stressful. Understanding how herbivorous mammals will respond to ambient temperature is imperative to accurately predict the impacts of climate change.

Cold temperature improves tannin tolerance in a granivorous rodent

“…While we lack specific information about particulars of liver enzymes and gene expression for mice in the present study, we speculate that this result may reflect a difference in hepatic gene expression driven by ambient temperature. Connors et al () found a similar interaction between ambient temperature and PSM ingestion on gene expression in woodrats. They found that differential gene expression in the liver was greater at a cooler temperature compared to a warmer temperature on a control diet, and that even though the warm temperature was within the thermal neutral zone, gene expression at this temperature indicated a stressed state.…”

“…Captive feeding experiments revealed that woodrats chose to eat significantly less terpene‐rich juniper extract at a warmer temperature (Dearing, Forbey, McLister, & Santos, ) and that a warm temperature reduced the tolerance of woodrats to the toxins in creosote (Kurnath, Merz, & Dearing, ). Further studies have shown that the effects of temperature on PSM toxicity may be related to liver function, with warmer temperatures resulting in reduced hepatic gene expression and slower clearance rates of hypnotic agents (Connors, Malenke, & Dearing, ; Kurnath & Dearing, ). The liver is known to play a major role in the acclimation of animals to a toxin‐rich diet.…”

“…Previous studies have suggested that consumption of PSMs in cold conditions may have thermoregulatory benefits for wild mammals as the heat generated by the metabolism of toxins in the liver may help to maintain core temperature (Dearing, ; Forbey et al, ; McLister, Sorensen, & Dearing, ). Conversely, changes induced by lower temperatures, such as changes to digestive tract morphology (Eto et al, ; Hammond & Wunder, ) or increased enzyme production (Connors et al, ), may act to improve tannin tolerance. There is a natural link between acorn predation and cold ambient temperature, where tannin‐rich acorns become the dominant food source over winter and an animal's ability to consume acorns and tolerate tannins may determine their winter survival and reproduction.…”

“…that the effects of temperature on PSM toxicity may be related to liver function, with warmer temperatures resulting in reduced hepatic gene expression and slower clearance rates of hypnotic agents (Connors, Malenke, & Dearing, 2017;Kurnath & Dearing, 2013). The liver is known to play a major role in the acclimation of animals to a toxin-rich diet.…”

“…Previous studies have suggested that consumption of PSMs in cold conditions may have thermoregulatory benefits for wild mammals as the heat generated by the metabolism of toxins in the liver may help to maintain core temperature (Dearing, 2013;Forbey et al, 2009;McLister, Sorensen, & Dearing, 2004). Conversely, changes induced by lower temperatures, such as changes to digestive tract morphology (Eto et al, 2016;Hammond & Wunder, 1995) or increased enzyme production (Connors et al, 2017), may act to improve tannin tolerance.…”