A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila

Beshel, Jennifer; Dubnau, Josh; Zhong, Yi

doi:10.1016/j.cmet.2016.12.013

Cited by 49 publications

(66 citation statements)

References 39 publications

(66 reference statements)

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“…For misexpression of transgenes, we utilized the GAL4/UAS system in flies [36]. The following stocks were obtained from the Bloomington Drosophila Stock Center, Bloomington, In, USA (supported by NIH grant P40OD018537) and used in this study: w*; Btl-GAL4, UAS-Act5C:GFP/CyO, lacZ (RRID:BDSC_8807); w 1118 , UAS-Dcr-2; Pin 1 /CyO (RRID: BDSC_24644); w 1118 ; 10XStat92E-GFP (RRID:BDSC_26197); UAS-os RNAi (RRID:BDSC_28722) [37]; UAS-upd RNAi (RRID:BDSC_33680) [38]; UAS-os2 RNAi (RRID: BDSC_33949) [37]; UAS-upd2 RNAi (RRID:BDSC_33988) [38]; w*, upd2D (RRID:BDSC_55727) [22]; and hs-FLP; Act5-C>y + >GAL4, UAS-GFP [39]. The following stocks were gifts from Douglas A. Harrison: UAS-ET (FBal0264424) [40]; y 1 , sc*, v 1 ; UAS-dome RNAi (RRID:BDSC_32860) [37]; y 1 , v 1 ; UAS-Stat92E RNAi (RRID:BDSC_33637) [37]; w*; UAS-hop/ CyO (RRID:BDSC_79033) [41]; Upd-GAL4, w* (RRID: BDSC_26796); UAS-iupd3 (FBal0177288) [42]; Upd3-GAL4, UAS-upd3-GFP/CyO; Dr/TM6B (cross between FBal0181583 and FBal0302834) [27]; and y 1 , sc*, v 1 ; UAS-upd3 RNAi (RRID:BDSC_32859) [43].…”

Section: Fly Stocks and Culturementioning

confidence: 99%

JAK/STAT signaling is involved in air sac primordium development of Drosophila melanogaster

Powers

Srivastava

2019

FEBS Letters

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The dorsal thoracic air sacs in fruit flies (Drosophila melanogaster) are functionally and developmentally comparable to human lungs. The progenitors of these structures, air sac primordia (ASPs), invasively propagate into wing imaginal disks, employing mechanisms similar to those that promote metastasis in malignant tumors. We investigated whether Janus kinase/signal transducer and activator of transcription JAK/STAT signaling plays a role in the directed morphogenesis of ASPs. We find that JAK/STAT signaling occurs in ASP tip cells and misexpression of core components in the JAK/STAT signaling cascade significantly impedes ASP development. We further identify Upd2 as an activating ligand for JAK/STAT activity in the ASP. Together, these data constitute a considerable step forward in understanding the role of JAK/STAT signaling in ASPs and similar structures in mammalian models.

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Section: Fly Stocks and Culturementioning

confidence: 99%

JAK/STAT signaling is involved in air sac primordium development of Drosophila melanogaster

Powers

Srivastava

2019

FEBS Letters

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“…While neuronal derived Upd1 regulates feeding behavior by inhibiting the food-seeking neuropeptide-Y (NPY) circuit (Beshel et al, 2017), Upd2 is a secreted factor produced from the fat body in response to dietary fat and sugars (Rajan and Perrimon, 2012). The physiological roles of Upd2 and Leptin are similar in the context of response to nutrient deprivation and energy sensing.…”

Section: Introductionmentioning

confidence: 99%

A Mechanism Coupling Systemic Energy Sensing to Adipokine Secretion

et al. 2017

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Summary Adipocytes sense systemic nutrient status and systemically communicate this information by releasing adipokines. The mechanisms which couple nutritional state to adipokine release are unknown. Here, we investigated how Unpaired 2 (Upd2), a structural and functional ortholog of the primary human adipokine Leptin, is released from Drosophila fat cells. We find that GRASP, an unconventional secretion pathway component, is required for Upd2 secretion. In nutrient rich fat cells, GRASP clusters in close proximity to apical side of lipid droplets (LDs). During nutrient deprivation, Glucagon mediated increase in Calcium (Ca2+) levels, via Calmodulin kinase II (CaMKII) phosphorylation, inhibits proximal GRASP localization to LDs. Using a heterologous cell system, we show that human Leptin secretion is also regulated by Ca2+ and CaMKII. In summary, we describe a mechanism by which increased cytosolic Ca2+ negatively regulates adipokine secretion and have uncovered an evolutionarily conserved molecular link between intracellular Ca2+ levels and energy homeostasis.

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“…At the molecular level, a number of signaling molecules act to control feeding in the brain. One such cytokine is Unpaired 1 (Upd1), a leptin-related protein that controls food intake and body weight gain in response to a high fat diet (Beshel et al, 2017). Upd1-expressing neurons suppress the secretion of neuropeptide F (NPF), the fly analog of the mammalian orexigenic neuropeptide Y.…”

Section: Musclementioning

confidence: 99%

Drosophilaas a model to study obesity and metabolic disease

Musselman

Kühnlein

2018

Journal of Experimental Biology

169

130

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Excess adipose fat accumulation, or obesity, is a growing problem worldwide in terms of both the rate of incidence and the severity of obesity-associated metabolic disease. Adipose tissue evolved in animals as a specialized dynamic lipid storage depot: adipose cells synthesize fat (a process called lipogenesis) when energy is plentiful and mobilize stored fat (a process called lipolysis) when energy is needed. When a disruption of lipid homeostasis favors increased fat synthesis and storage with little turnover owing to genetic predisposition, overnutrition or sedentary living, complications such as diabetes and cardiovascular disease are more likely to arise. The vinegar fly Drosophila melanogaster (Diptera: Drosophilidae) is used as a model to better understand the mechanisms governing fat metabolism and distribution. Flies offer a wealth of paradigms with which to study the regulation and physiological effects of fat accumulation. Obese flies accumulate triacylglycerols in the fat body, an organ similar to mammalian adipose tissue, which specializes in lipid storage and catabolism. Discoveries in Drosophila have ranged from endocrine hormones that control obesity to subcellular mechanisms that regulate lipogenesis and lipolysis, many of which are evolutionarily conserved. Furthermore, obese flies exhibit pathophysiological complications, including hyperglycemia, reduced longevity and cardiovascular functionsimilar to those observed in obese humans. Here, we review some of the salient features of the fly that enable researchers to study the contributions of feeding, absorption, distribution and the metabolism of lipids to systemic physiology.

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A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila

Cited by 49 publications

References 39 publications

JAK/STAT signaling is involved in air sac primordium development of Drosophila melanogaster

JAK/STAT signaling is involved in air sac primordium development of Drosophila melanogaster

A Mechanism Coupling Systemic Energy Sensing to Adipokine Secretion

Drosophilaas a model to study obesity and metabolic disease

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