Cross-talk between the fat body and brain regulates insect developmental arrest

Abstract

Developmental arrest, a critical component of the life cycle in animals as diverse as nematodes (dauer state), insects (diapause), and vertebrates (hibernation), results in dramatic depression of the metabolic rate and a profound extension in longevity. Although many details of the hormonal systems controlling developmental arrest are well-known, we know little about the interactions between metabolic events and the hormones controlling the arrested state. Here, we show that diapause is regulated by an interplay between blood-borne metabolites and regulatory centers within the brain. Gene expression in the fat body, the insect equivalent of the liver, is strongly suppressed during diapause, resulting in low levels of tricarboxylic acid (TCA) intermediates circulating within the blood, and at diapause termination, the fat body becomes activated, releasing an abundance of TCA intermediates that act on the brain to stimulate synthesis of regulatory peptides that prompt production of the insect growth hormone ecdysone. This model is supported by our success in breaking diapause by injecting a mixture of TCA intermediates and upstream metabolites. The results underscore the importance of cross-talk between the brain and fat body as a regulator of diapause and suggest that the TCA cycle may be a checkpoint for regulating different forms of animal dormancy.prothoracicotropic hormone | glucose | pyruvate A s days shorten in late summer and temperatures drop, many insects respond by entering an overwintering diapause, a form of developmental arrest characterized by metabolic depression. The major endocrine events that regulate diapause are fairly well-understood. In larvae and pupae, the arrest is usually a consequence of the brain's failure to produce or release prothoracicotropic hormone (PTTH), a neuropeptide needed to stimulate the prothoracic gland to synthesize the steroid hormones ecdysteroids (20-hydroxyecdysone is the most active form and will be referred to hereafter as ecdysone) (1). Without ecdysone, the insect remains locked in a developmental arrest that persists as long as ecdysone is absent.Specific patterns of gene expression and unique metabolic profiles characterize diapause (2-4), but the interactions between genes, metabolites, and the major endocrine centers are poorly known. One of the most conspicuous metabolic patterns during diapause in insects and dormancy in other animals (5-7) is a shift to anaerobic metabolism favoring glycolysis and gluconeogenesis. Although it is usually assumed that changes in abundance of specific metabolites are downstream responses to the diapause program, the demonstration that elevated sorbitol is the cause, rather than the consequence, of developmental arrest in embryos of the silk moth (8) suggests the possibility that the metabolite profile itself may influence the diapause decision. This possibility is tested here by monitoring changes in metabolite abundance in association with diapause and then showing that artificially boosting the abundance of nondiapause met...

Cross generation plasticity in cold hardiness is associated with diapause, but not the non-diapause developmental pathway, in the blowfly, Calliphora vicina

“…However, whether levels of glucose change as part of the diapause programme has never been investigated in this species. Increased levels of glucose have been strongly associated with diapause in several other insects (Pullin and Wolda, 1993; Overgaard et al, 2007;Robert Michaud et al, 2008; Hou et al, 2009;Ragland et al, 2010;Xu et al, 2012), with a hypothesised role in in enhancing cold tolerance. We noted a threefold increase in glucose concentration in C. vicina D larvae (Table 2), which, combined with greater cold tolerance (Fig.…”

Comparative proteomic analysis of silkworm fat body after knocking out fibroin heavy chain gene: a novel insight into cross-talk between tissues

“…It is considered that this hemolymph system will be convenient for tissues to communicate and play roles coordinately. For example, the communication between the fat body and brain in insect could regulate the developmental arrest (Xu et al 2012). The size of the salivary gland is significantly smaller after ablating the fat body cells (Liu et al 2009).…”

Molecular basis of chill resistance adaptations in poikilothermic animals

“…Patterns of metabolic downregulation and modulation of energy production in response to both cold and diapause have a number of common themes across species, most notably the reduction of tricarboxylic acid (TCA) cycle intermediates and a larger dependence on glycolytic and gluconeogenic pathways (Colinet et al., 2012b;Michaud and Denlinger, 2007;Ragland et al, 2010;Xu et al, 2012). Metabolites that are upregulated in response to cold and diapause are dominated by those thought to enhance cold stress tolerance, including: sugars, e.g.…”

“…RCH uniquely perturbed the urea cycle and upregulated glutamine, cystathionine, sorbitol and urea, while only leucine was upregulated as part of diapause. As with other 'omic levels, separating causative responses from secondary effects is not easy, but they can constrain and direct what is an open and bias-free search for a wider range of possibilities than might occur through conventional hypothesis-driven approaches.Patterns of metabolic downregulation and modulation of energy production in response to both cold and diapause have a number of common themes across species, most notably the reduction of tricarboxylic acid (TCA) cycle intermediates and a larger dependence on glycolytic and gluconeogenic pathways (Colinet et al., 2012b;Michaud and Denlinger, 2007;Ragland et al, 2010;Xu et al, 2012). Metabolites that are upregulated in response to cold and diapause are dominated by those thought to enhance cold stress tolerance, including: sugars, e.g.…”