Opposing Effects of Dietary Protein and Sugar Regulate a Transcriptional Target of Drosophila Insulin-like Peptide Signaling

Buch, Susanne R.; Melcher, Christoph; Bauer, Matthias; Katzenberger, Joerg D.; Pankratz, Michael J.

doi:10.1016/j.cmet.2008.02.012

Cited by 163 publications

(208 citation statements)

References 38 publications

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“…This finding is consistent with our general knowledge that insulin signaling is rapidly modulated in response to changes in nutrition in animals, including Drosophila (26,27). The fact that the feeding activities of GS1189 larvae continuously remained very low suggested that regulation of feeding potencies by insulin signaling was somehow disordered in the mutant animals.…”

Section: Discussionsupporting

confidence: 80%

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

Ryuda

Tsuzuki

Matsumoto

et al. 2011

Journal of Biological Chemistry

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Background:Little is known about the molecular mechanisms underlying animal feeding behavior. Result: We identified a new gene, Anorexia (Anox), which encodes an acyl-CoA binding protein with an ankyrin repeat domain. Conclusion:Anox has an essential role in controlling feeding activities in Drosophila by regulating insulin signaling. Significance: Identification of Anox can develop a better knowledge of mechanisms underlying animal feeding behavior.

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Section: Discussionsupporting

confidence: 80%

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

Ryuda

Tsuzuki

Matsumoto

et al. 2011

Journal of Biological Chemistry

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“…2A). As expected, this group also included known downstream targets of IIS, for example the target of brain insulin (tobi) (40). These results were confirmed independently for selected genes by RT-PCR (Fig.…”

Section: Iis In Oenocytes Is Crucial To Maintain Starvation Resistancsupporting

confidence: 66%

Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes

Chatterjee

Katewa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liverlike oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulinlike peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance.T o maintain metabolic homeostasis during fasting periods, metazoans have to coordinate the mobilization of glycogen, lipids, and protein, ensuring an adequate energy supply across tissues. In addition to tissue-autonomous metabolic adjustments, endocrine signals are therefore critical components of the fasting response (1, 2). In mammals, the liver is central to adjusting intermediary metabolism during fasting. Starvation stimulates lipid accumulation in hepatocytes, which oxidize these lipids to provide energy in the form of ketone bodies for other tissues. Hepatocytes also respond to glucagon and insulin signals to control the expression of enzymes involved in glycogenolysis and gluconeogenesis, lipolysis, fatty acid oxidation, and ketogenesis, all regulated by a battery of transcription factors that include forkhead box O (Foxo), cAMP-response element binding (CREB), peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1a), and hepatocyte nuclear factor 4a (HNF4a) (3-5). At the same time, the liver integrates a suite of endocrine signals derived from major energy storing and consuming tissues, such as the brain, the adipose tissue, and the muscle (1). Deregulation of these processes can lead to hepatic steatosis and is a major cause of metabolic diseases, including diabetes and metabolic syndrome (1,3,6).Drosophila has emerged as a productive model organism in which to characterize the endocrine regulation of metabolic adaptation (7,8). The central function of the liver in metabolic adaptation of flies is shared by the fat body and oenocytes. Whereas the fat body is an important glycogen and fat storage organ in flies, it also serves as an endocrine organ to coordinate metabolic homeostasis (9-12). Oenocytes have a critical role in lipid mobilization and turnover in larvae, accumulating lipids during s...

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“…However, a role of AKH in AMPK activation, which would establish an autoregulatory loop, has not been addressed. Similarly, up-regulation of Akh on the transcriptional level in response to loss of insulin signaling has been described in Drosophila (Buch et al 2008). But again, it is unclear whether this antagonistic regulation involves an autoregulatory mechanism.…”

Section: Autoregulation Of the Akh Genementioning

confidence: 99%

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

et al. 2015

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Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation.KEYWORDS Drosophila; adipokinetic hormone; adipokinetic hormone precursor-related peptide; energy homeostasis; stress resistance E NERGY homeostasis requires continuous compensation for fluctuations in the energy expenditure and availability of food resources. Organisms thus build up reserves under positive energy balance and catabolize them when the balance turns negative to retain stable levels of circulating energy fuel. Insulin signaling induces the uptake of excessive circulating sugars, thus promoting reserve accumulation (reviewed, e.g., in Saltiel and Kahn 2001; Cohen 2006), whereas energy mobilization is under the control of glucagon and glucocorticoid signaling in mammals (reviewed, e.g., in Rui 2014;Charron and Vuguin 2015) and adipokinetic hormone (AKH) signaling in insects (reviewed, e.g., in Van der Horst 2003;Lorenz and Gäde 2009;Bednářová et al. 2013a). Consistent with their fundamental physiological function in energy mobilization, AKHs are found not only in insects, but are common in Protostomia, where they have been identified both in Ecdyszoa (in Arthropoda, Tardigrada, and Priapulida) and Lophotrochozoa (in Mollusca, Rotifera, and Annelida) (Gäde 2009;Hauser and Grimmelikhuijzen 2014). Nevertheless, physiological functions of AKHs have been studied mainly in Arthropoda. Similar to mammals, also insects store lipids in the form of triacylglycerides (TGs) and as carbohydrates in the form of glycogen. The main storage organ for lipid and glycogen in insects is the fat body, which can thus b...

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Opposing Effects of Dietary Protein and Sugar Regulate a Transcriptional Target of Drosophila Insulin-like Peptide Signaling

Cited by 163 publications

References 38 publications

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

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