Dual Lipolytic Control of Body Fat Storage and Mobilization in Drosophila

Grönke, Sebastian; Müller, Günter; Hirsch, Jochen G.; Fellert, Sonja; Andreou, Alexandra Z.; Haase, Tobias; Jäckle, Herbert; Kühnlein, Ronald P.

doi:10.1371/journal.pbio.0050137

Cited by 291 publications

(449 citation statements)

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“…Intriguingly, Drosophila Akh and AkhR are already expressed at embryogenesis (Kim and Rulifson 2004;Lee and Park 2004;Grönke et al 2007), suggesting that AKH might have biological functions in energy mobilization from early developmental stages onwards. However, our data show that AKH, APRP, and AKHR are dispensable for embryonic development.…”

Section: Developmental Roles Of Akh Signalingmentioning

confidence: 99%

“…Mobilization of energy reserves for oogenesis was predicted to be AKH regulated ( (Grönke et al 2007;Bharucha et al 2008). In the current study, we did not detect any changes in fecundity in the absence of AKH signaling, suggesting that in Drosophila, oogenesisdependent fat mobilization is under the control of an alternative lipolytic pathway.…”

Section: Akh Signaling Is Not Required For Drosophila Reproductionmentioning

confidence: 99%

“…Even though no role of APRP was described so far (Hatle and Spring 1999), its evolutionary conservation, common ancestry with mammalian growth hormone-releasing factors (Clynen et al 2004), and release upon stimulation with melatonin (Huybrechts et al 2005) all argue in favor of an endocrine function of this peptide. Thus, unequivocal study of AKH and APRP functions requires creation of specific mutants, which we describe in this study.Biochemical studies identified a single Drosophila AKHR receptor (Park et al 2002;Staubli et al 2002), which has been functionally analyzed in vivo (Grönke et al 2007;Bharucha et al 2008). However, these studies do not exclude AKH signal transmission via other receptor pathways.…”

mentioning

confidence: 99%

“…Nevertheless, it is possible that other pathways compensate for absence of AKH, thus obscuring the detection of AKH-related developmental functions in the mutants. A prime candidate for such an alternative lipid mobilization pathway involves the Brummer lipase, as bmm mutants are embryonic lethal (Grönke et al 2005), and the gene is known to work in parallel with AkhR in starvation-induced storage fat mobilization in Drosophila adults (Grönke et al 2007). Alternatively, AKH signaling might instead have finetuning functions that would become obvious only under particular suboptimal conditions.…”

mentioning

confidence: 99%

“…Biochemical studies identified a single Drosophila AKHR receptor (Park et al 2002;Staubli et al 2002), which has been functionally analyzed in vivo (Grönke et al 2007;Bharucha et al 2008). However, these studies do not exclude AKH signal transmission via other receptor pathways.…”

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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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Section: Developmental Roles Of Akh Signalingmentioning

confidence: 99%

Section: Akh Signaling Is Not Required For Drosophila Reproductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

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Hormonal and nutritional regulation of insect fat body development and function

Liu

et al. 2009

Arch Insect Biochem Physiol

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The insect fat body is an organ analogue to vertebrate adipose tissue and liver and functions as a major organ for nutrient storage and energy metabolism. Similar to other larval organs, fat body undergoes a developmental ''remodeling'' process during the period of insect metamorphosis, with the massive destruction of obsolete larval tissues by programmed cell death and the simultaneous growth and differentiation of adult tissues from small clusters of progenitor cells. Genetic ablation of Drosophila fat body cells during larval-pupal transition results in lethality at the late pupal stage and changes sizes of other larval organs indicating that fat body is the center for pupal development and adult formation. Fat body development and function are largely regulated by several hormonal (i.e. insulin and ecdysteroids) and nutritional signals, including oncogenes and tumor suppressors in these pathways. Combining silkworm physiology with fruitfly genetics might provide a valuable system to understand the mystery of hormonal regulation of insect fat body development and function. C 2009 Wiley Periodicals, Inc.

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