Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control

Song, Wei; Cheng, Daojun; Hong, Shangyu; Sappe, Benoit; Hu, Yanhui; Wei, Neil; Zhu, Changqi C.; O’Connor, Michael B.; Pissios, Pavlos; Perrimon, Norbert

doi:10.1016/j.cmet.2017.01.002

Cited by 100 publications

(148 citation statements)

References 65 publications

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“…4D), suggesting that NF-κB/Rel signaling promotes Actβ production. We also confirmed activation of NF-κB/Rel signaling in complex I-perturbed muscle by using a Diptericin-GFP (Dpt-GFP) reporter (14,19) (Fig. 4C).…”

Section: The Ros/nf-κb Cascade Autonomously Regulates Actβ Expression Insupporting

confidence: 51%

“…In addition to acting as a neuropeptide expressed in central or peripheral nerves (24,25), Actβ also acts as an endocrine peptide derived from enteroendocrine cells to target the fat body via the Babo receptor (14). Actβ is expressed at low levels in wild-type muscle (14); however, we observed a significant induction of Actβ expression when complex I was perturbed in muscle cells, suggesting that mitochondrial injury can turn on Actβ expression in the muscle to subsequently regulate fat body function.…”

Section: Discussioncontrasting

confidence: 39%

“…Actβ is expressed at low levels in wild-type muscle (14); however, we observed a significant induction of Actβ expression when complex I was perturbed in muscle cells, suggesting that mitochondrial injury can turn on Actβ expression in the muscle to subsequently regulate fat body function. Actβ/Babo signaling has been shown to enhance the response to Akh in the larval fat body (14).…”

Section: Discussionmentioning

confidence: 56%

“…2 G and H). We previously found that midgut-induced activation of TGF-β signaling in the fat body leads to metabolic dysregulation (14). Based on this idea, we speculated that nonautonomous activation of TGF-β signaling also participates in muscle-to-fat body communication.…”

Section: Modulation Of Tgf-β Signaling In the Fat Body Upon Muscle MImentioning

confidence: 99%

“…For example, activin A is the homolog of Drosophila Actβ and is an important regulator of lipid metabolism and mitochondrial activity (14,20). To ask whether functional conservation extends to ROS-induced Activin production in mammals, we treated C2C12 myoblasts with rotenone, a well-established complex I inhibitor (21), which resulted in rapid and robust ROS elevation as indicated by CellROX, a dye that specifically detects ROS (Fig.…”

Section: The Ros/nf-κb Cascade Autonomously Regulates Actβ Expression Inmentioning

confidence: 99%

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Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model

Song

Owusu-Ansah

et al. 2017

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

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Mitochondrial dysfunction has been associated with obesity and metabolic disorders. However, whether mitochondrial perturbation in a single tissue influences mitochondrial function and metabolic status of another distal tissue remains largely unknown. We analyzed the nonautonomous role of muscular mitochondrial dysfunction in Drosophila. Surprisingly, impaired muscle mitochondrial function via complex I perturbation results in simultaneous mitochondrial dysfunction in the fat body (the fly adipose tissue) and subsequent triglyceride accumulation, the major characteristic of obesity. RNA-sequencing (RNA-seq) analysis, in the context of muscle mitochondrial dysfunction, revealed that target genes of the TGF-β signaling pathway were induced in the fat body. Strikingly, expression of the TGF-β family ligand, Activin-β (Actβ), was dramatically increased in the muscles by NF-κB/Relish (Rel) signaling in response to mitochondrial perturbation, and decreasing Actβ expression in mitochondrial-perturbed muscles rescued both the fat body mitochondrial dysfunction and obesity phenotypes. Thus, perturbation of muscle mitochondrial activity regulates mitochondrial function in the fat body nonautonomously via modulation of Activin signaling.mitochondrial synchrony | Activin-β | complex I perturbation | NF-κB/Relish | lipid metabolism I ndividual organs in a multicellular organism, besides performing their respective roles, must communicate with other organs to maintain systemic homeostasis. The central nervous system (CNS) in particular integrates information regarding the status of peripheral metabolic processes via hormonal signaling and directs energy homeostasis and feeding behavior (1). In addition, metabolic changes in a peripheral organ can affect the physiology of other peripheral organs (2, 3). The skeletal muscle system, which is newly recognized as playing endocrine-related roles, produces myokines after exercise to target other metabolic organs (liver, adipose tissue, pancreas, gut, and bone) and modulates systemic energy homeostasis (4).Mitochondria are semiautonomous organelles that integrate multiple physiological signals. Growing evidence indicates that mitochondrial alterations in one organ leads to abnormalities in biological processes in distal organs through hormonal signaling (5, 6). In addition to exercise, which induces mitochondrial activity and improves muscle performance, mitochondrial perturbationassociated muscle injury is also sufficient to modulate functions of other organs and change systemic outcomes via myokine production. For example, in mammals, mitochondrial dysfunction due to disruption of autophagic function in skeletal muscles results in elevated production of muscular FGF21 that triggers browning of white adipose tissue and increases lipid mobilization (7). Further, in Drosophila, mild mitochondrial distress in adult muscles delays aging via an increase of muscular ImpL2 production and remote suppression of insulin signaling in the fat body and brain (8). Despite these examples, molecula...

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Section: The Ros/nf-κb Cascade Autonomously Regulates Actβ Expression Insupporting

confidence: 51%

Section: Discussioncontrasting

confidence: 39%

Section: Discussionmentioning

confidence: 56%

Section: Modulation Of Tgf-β Signaling In the Fat Body Upon Muscle MImentioning

confidence: 99%

Section: The Ros/nf-κb Cascade Autonomously Regulates Actβ Expression Inmentioning

confidence: 99%

See 3 more Smart Citations

Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model

Song

Owusu-Ansah

et al. 2017

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

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Characterization of a Nilaparvata lugens (Stål) brummer gene and analysis of its role in lipid metabolism

Zhou

You

et al. 2017

Arch Insect Biochem Physiol

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The brummer (bmm) genes encode the lipid storage droplet-associated triacylglycerols (TAG) lipases, which belong to the Brummer/Nutrin subfamily. These enzymes hydrolyze the ester bonds in TAG in lipid metabolism and act in insect energy homeostasis. Exposure to some agricultural chemicals leads to increased fecundity, which necessarily involves lipid metabolism, in some planthopper species. However, the biological roles of bmm in planthopper lipid storage and mobilization have not been investigated. Here, the open reading frame (ORF) of bmm (Nlbmm) was cloned and sequenced from the brown planthopper (BPH; Nilaparvata lugens). The ORF is 1014 bp encoding 338 amino acid residues. Nlbmm contained patatin domains and shared considerable evolutionary conservation with other insect bmms. Nlbmm is highly expressed in the fat body, consistent with its roles in lipid metabolism. Injection with Nlbmm double-stranded RNA (dsNlbmm) led to reduced Nlbmm mRNA accumulation, but did not influence expression of several genes related to lipid synthesis including acyl-CoA-binding protein (ACBP), acetyl-CoA carboxylase (ACC), and a lipophorin receptor (LpR). Nlbmm knockdown led to increased TAG contents in whole bodies, accumulation of total fat body lipid, and decreased hemolymph lipid content. Nlbmm knockdown did not influence the synthesis and distribution of glycerol. We infer that Nlbmm acts in TAG breakdown and fat metabolism in N. lugens.

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Endocrine Regulation of Energy Balance by Drosophila TGF‐β/Activins

et al. 2018

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The Transforming growth factor beta (TGF‐β) family of secreted proteins regulates a variety of key events in normal development and physiology. In mammals, this family, represented by 33 ligands, including TGF‐β, activins, nodal, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs), regulate biological processes as diverse as cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine functions. In Drosophila, only 7 members of this family are present, with 4 TGF‐β/BMP and 3 TGF‐β/activin ligands. Studies in the fly have illustrated the role of TGF‐β/BMP ligands during embryogenesis and organ patterning, while the TGF‐β/activin ligands have been implicated in the control of wing growth and neuronal functions. In this review, we focus on the emerging roles of Drosophila TGF‐β/activins in inter‐organ communication via long‐distance regulation, especially in systemic lipid and carbohydrate homeostasis, and discuss findings relevant to metabolic diseases in humans.

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Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control

Cited by 100 publications

References 65 publications

Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model

Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model

Characterization of a Nilaparvata lugens (Stål) brummer gene and analysis of its role in lipid metabolism

Endocrine Regulation of Energy Balance by Drosophila TGF‐β/Activins

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