Lipid-Mediated Mechanisms of Thermal Adaptation and Thermoregulatory Behavior in Animals.

Temperature affects a variety of cellular processes because the molecular motion of cellular constituents and the rate of biochemical reactions are sensitive to temperature changes. Thus, the adaptation to temperature is necessary to maintain cellular functions during temperature fluctuation, particularly in poikilothermic organisms. For a wide range of organisms, cellular lipid molecules play a pivotal role during thermal adaptation. Temperature changes affect the physicochemical properties of lipid molecules, resulting in the alteration of cell membrane-related functions and energy metabolism. Since the chemical structures of lipid molecules determine their physicochemical properties and cellular functions, cellular lipids, particularly fatty acid-containing lipid molecules, are remodeled as a thermal adaptation response to compensate for the effects of temperature change. In this chapter, we first introduce the structure and biosynthetic pathway of fatty acid-containing lipid molecules, such as phospholipid and triacylglycerol, followed by a description of the cellular lipid-mediated mechanisms of thermal adaptation and thermoregulatory behavior in animals.

Regulation of thermoregulatory behavior by commensal bacteria in Drosophila.

Commensal bacteria affect many aspects of host physiology. In this study, we focused on the role of commensal bacteria in the thermoregulatory behavior of Drosophila melanogaster. We demonstrated that the elimination of commensal bacteria caused an increase in the preferred temperature of Drosophila third-instar larvae without affecting the activity of transient receptor potential ankyrin 1 (TRPA1)-expressing thermosensitive neurons. We isolated eight bacterial strains from the gut and culture medium of conventionally reared larvae and found that the preferred temperature of the larvae was decreased by mono-association with Lactobacillus plantarum or Corynebacterium nuruki. Mono-association with these bacteria did not affect the indices of energy metabolism such as ATP and glucose levels of larvae, which are closely linked to thermoregulation in animals. Thus, we show a novel role for commensal bacteria in host thermoregulation and identify two bacterial species that affect thermoregulatory behavior in Drosophila.

Different mechanisms for selective transport of fatty acids using a single class of lipoprotein in Drosophila.

In mammals, lipids are selectively transported to specific sites using multiple classes of lipoproteins. However, in Drosophila, a single class of lipoproteins, lipophorin, carries more than 95% of the lipids in the hemolymph. Although a unique ability of the insect lipoprotein system for cargo transport has been demonstrated, it remains unclear how this single class of lipoproteins selectively transports lipids. In this study, we carried out a comparative analysis of the fatty-acid composition among lipophorin, the CNS, and CNS-derived cell lines and investigated the transport mechanism of fatty acids, particularly focusing on the transport of PUFAs in Drosophila We showed that PUFAs are selectively incorporated into the acyl chains of lipophorin phospholipids and effectively transported to CNS through lipophorin receptor-mediated endocytosis of lipophorin. In addition, we demonstrated that C14 fatty acids are selectively incorporated into the diacylglycerols (DAGs) of lipophorin and that C14 fatty-acid-containing DAGs are spontaneously transferred from lipophorin to the phospholipid bilayer. These results suggest that PUFA-containing phospholipids and C14 fatty-acid-containing DAGs in lipophorin could be transferred to different sites by different mechanisms to selectively transport fatty acids using a single class of lipoproteins.

Functional relationship between peripheral thermosensation and behavioral thermoregulation.

Thermoregulation is a fundamental mechanism for maintaining homeostasis in living organisms because temperature affects essentially all biochemical and physiological processes. Effector responses to internal and external temperature cues are critical for achieving effective thermoregulation by controlling heat production and dissipation. Thermoregulation can be classified as physiological, which is observed primarily in higher organisms (homeotherms), and behavioral, which manifests as crucial physiological functions that are conserved across many species. Neuronal pathways for physiological thermoregulation are well-characterized, but those associated with behavioral regulation remain unclear. Thermoreceptors, including Transient Receptor Potential (TRP) channels, play pivotal roles in thermoregulation. Mammals have 11 thermosensitive TRP channels, the functions for which have been elucidated through behavioral studies using knockout mice. Behavioral thermoregulation is also observed in ectotherms such as the fruit fly, Drosophila melanogaster. Studies of Drosophila thermoregulation helped elucidate significant roles for thermoreceptors as well as regulatory actions of membrane lipids in modulating the activity of both thermosensitive TRP channels and thermoregulation. This review provides an overview of thermosensitive TRP channel functions in behavioral thermoregulation based on results of studies involving mice or Drosophila melanogaster.

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila.

Polyunsaturated fatty acids (PUFAs) play crucial roles in adaptation to cold environments in a wide variety of animals and plants. However, the mechanisms by which PUFAs affect thermoregulatory behaviour remain elusive. Thus, we investigated the roles of PUFAs in thermoregulatory behaviour of Drosophila melanogaster. To this end, we generated transgenic flies expressing Caenorhabditis elegans Δ12 fatty acid desaturase (FAT-2), which converts mono-unsaturated fatty acids to PUFAs such as linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)]. Neuron-specific expression of FAT-2 using the GAL4/UAS expression system led to increased contents of C18:2 (n-6)-containing phospholipids in central nerve system (CNS) and caused significant decreases in preferred temperature of third instar larvae. In genetic screening and calcium imaging analyses of thermoreceptor-expressing neurons, we demonstrated that ectopic expression of FAT-2 in TRPA1-expressing neurons led to decreases in preferred temperature by modulating neuronal activity. We conclude that functional expression of FAT-2 in a subset of neurons changes the thermoregulatory behaviour of D. melanogaster, likely by modulating quantities of PUFA-containing phospholipids in neuronal cell membranes.

Synthesis of omega-3 long-chain polyunsaturated fatty acid-rich triacylglycerols in an endemic goby, Gymnogobius isaza, from Lake Biwa, Japan.

It is commonly observed that freshwater fish contain lower amounts of omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), such as eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), than marine fish species. In this study, we performed a detailed comparative analysis of phospholipids (PLs) and triacylglycerols (TAGs) from Gymnogobius isaza, a freshwater goby endemic to Lake Biwa inhabiting the lake bottom, and Gymnogobius urotaenia, a related goby that inhabits the shore of Lake Biwa. We found that tissues from G. isaza contain remarkably high amounts of omega-3 LC-PUFAs in both PLs and TAGs. Mass spectrometry analysis of TAGs demonstrated that the most abundant TAG molecular species were TAG (16:0/18:1/20:5), followed by TAG (14:0/18:1/20:5), in which EPA is incorporated into TAG at either the sn-1 or sn-3 positions. We isolated cDNAs encoding acyl-CoA: diacylglycerol acyltransferase designated as GiDGAT1 and GiDGAT2, from G. isaza. Expression studies using a neutral lipid-deficient Saccharomyces cerevisiae mutant strain demonstrated that both GiDGAT1 and GiDGAT2 possessed diacylglycerol acyltransferase activity, and preferential incorporation of LC-PUFA into TAG was observed in the presence of GiDGAT1. This study revealed the novel lipid profiles of G. isaza and identified the enzymes that were involved in the production of PUFA-containing TAGs.