scholarly journals Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Arpan C Ghosh ◽  
Sudhir Gopal Tattikota ◽  
Yifang Liu ◽  
Aram Comjean ◽  
Yanhui Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Level ◽  
Lipid Synthesis ◽  
Tissue Lipid ◽  
Tor Signaling ◽  
Specific Expression ◽  
Signaling Axis ◽  
Organ Specific ◽  
Lipid Stores ◽  
Multicellular Organisms

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.

scholarly journals Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

2019 ◽  
Author(s):  
Arpan C. Ghosh ◽  
Sudhir G. Tattikota ◽  
Yifang Liu ◽  
Aram Comjean ◽  
Yanhui Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Synthesis ◽  
Rapid Expansion ◽  
List Type ◽  
Tissue Lipid ◽  
Mature Adult ◽  
Signaling Axis ◽  
Organ Specific ◽  
Lipid Stores ◽  
Multicellular Organisms

AbstractPDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine and endocrine mechanisms. Here, we investigated organ-specific roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/mTOR signaling cascade in the oenocytes. Additionally, we show that this signaling axis regulates the rapid expansion of adipose tissue lipid stores observed in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid levels are progressively restored via lipid synthesis. We find that pvf1 expression in the adult muscle increase rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits restoration of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating mTOR in hepatocyte-like cells.HighlightsMuscle specific Pvf1 protects mature adult flies from obesitySingle-nuclei RNA sequencing reveals that PvR, the receptor for Pvf1, is highly expressed in the Drosophila hepatocyte-like cells/oenocytes.PvR is required specifically in oenocytes to protect adult flies from obesityMuscle-to-oenocyte Pvf1 signaling activates PvR/Pi3K/Akt1/mTOR in the oenocytes to suppress lipid synthesisMuscle-derived Pvf1 helps terminate the rapid expansion of adipose tissue lipid stores in newly eclosed flies

scholarly journals Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maki Murakoshi ◽  
Tomohito Gohda ◽  
Eri Adachi ◽  
Saki Ichikawa ◽  
Shinji Hagiwara ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Tubular Damage ◽  
Standard Diet ◽  
Mrna Levels ◽  
High Fat ◽  
Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

scholarly journals The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

2021 ◽  
Vol 33 (3) ◽  
pp. 565-580.e7
Author(s):  
Suzhen Chen ◽  
Xiaoxiao Liu ◽  
Chao Peng ◽  
Chang Tan ◽  
Honglin Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ampk Signaling ◽  
Signaling Axis

Catecholaminergic innervation of white adipose tissue in Siberian hamsters

1995 ◽  
Vol 268 (3) ◽  
pp. R744-R751 ◽  
Author(s):  
T. G. Youngstrom ◽  
T. J. Bartness
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Neural Control ◽  
Fat Pad ◽  
Anterograde Transport ◽  
Siberian Hamsters ◽  
Lipid Stores ◽  
Catecholaminergic Innervation ◽  
Fat Pads

When Siberian hamsters are transferred from long summerlike days (LDs) to short winterlike days (SDs) they decrease their body weight, primarily as body fat. These SD-induced decreases in lipid stores are not uniform. Internally located white adipose tissue (WAT) pads are depleted preferentially of lipid, whereas the more externally located subcutaneous WAT pads are relatively spared. These data suggest a possible differential sympathetic neural control over catecholamine-induced lipolysis and that lipolytic rates are greater for internal vs. external WAT pads. Moreover, if these differential rates of lipolysis are due to differential sympathetic nervous system (SNS) drives on the pads, then fat pad-specific catecholaminergic innervation may exist. Therefore, we tested whether inguinal WAT (IWAT; an external pad) and epididymal WAT (EWAT; an internal pad) were innervated differentially. In addition, we tested whether norepinephrine (NE) turnover (TO) reflected the presumed greater SNS drive on EWAT vs. IWAT after SD exposure. Injections of fluorescent tract tracers [Fluoro-Gold or indocarbocyanine perchlorate (DiI)] demonstrated projections from the SNS ganglia T13-L3 to both fat pads. Retrograde labeling revealed a relatively separate pattern of distribution of labeled neurons in the ganglia projecting to each pad. In vivo anterograde transport of DiI resulted in labeling in both IWAT and EWAT that included staining around individual adipocytes and occasionally retrogradely labeled cells. The proportionately greater decrease in EWAT compared with IWAT mass after 5 wk of SD exposure was reflected in greater EWAT NE TO than found in their LD counterparts for this pad.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Unconventional Translation Initiation Factor EIF2A is required for Drosophila spermatogenesis

2021 ◽  
Author(s):  
David D Lowe ◽  
Denise Montell
Keyword(s):  
Mammalian Cells ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Male Sterile ◽  
Specific Expression ◽  
Transposon Insertion ◽  
Stress Related Genes ◽  
Male Specific ◽  
Multicellular Organisms

The eukaryotic initiation factor EIF2A is an unconventional translation factor required for initiation of protein synthesis from non-AUG codons from a variety of transcripts, including oncogenes and stress related genes in mammalian cells. Its function in multicellular organisms has not been reported. Here, we identify and characterize mutant alleles of the CG7414 gene, which encodes the Drosophila EIF2A ortholog. We identified that CG7414 undergoes sex-specific splicing that regulates its male-specific expression. We characterized a Mi{Mic} transposon insertion that disrupts the coding regions of all predicted isoforms and is a genetic null allele, and a PBac transposon insertion into an intron, which is a hypomorph. The Mi{Mic} allele is homozygous lethal, while the viable progeny from the hypomorphic PiggyBac allele are male sterile and female fertile. In dEIF2A mutant flies, sperm failed to individualize due to defects in F-actin cones and failure to form and maintain cystic bulges, ultimately leading to sterility. These results demonstrate that EIF2A is essential in a multicellular organism, both for normal development and spermatogenesis, and provide an entree into the elucidation of the role of EIF2A and unconventional translation in vivo.

scholarly journals Cell Type-Specific Expression and Coregulation of Murine Resistin and Resistin-Like Molecule-α in Adipose Tissue

2002 ◽  
Vol 16 (8) ◽  
pp. 1920-1930 ◽  
Author(s):  
Michael W. Rajala ◽  
Ying Lin ◽  
Mollie Ranalletta ◽  
Xiao Man Yang ◽  
Hao Qian ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Regulation ◽  
Stromal Vascular Fraction ◽  
Secretory Protein ◽  
Specific Expression ◽  
Acute Hyperglycemia ◽  
Cell Type Specific Expression ◽  
Negative Effect ◽  
Cell Type Specific ◽  
Exclusive Or

Abstract Adipocytes are the exclusive or predominant source of several secreted proteins that exert profound effects on systemic carbohydrate and lipid metabolism. Resistin, a 10-kDa adipose tissue specific secretory protein, has recently been implicated in exerting a negative effect on systemic insulin sensitivity. It is, however, not known how resistin mediates this insulin-desensitizing effect or what regulatory mechanisms control resistin expression. Resistin-like molecule-α (RELMα), a homolog of resistin originally identified by its upregulation in asthmatic lung, is another secreted protein expressed in adipose tissue. The regulation of RELMα in adipose tissue and its relationship to resistin expression has not been addressed so far. Here, we demonstrate that the expression of resistin and RELMα are similarly regulated in adipose tissue despite the fact that RELMα is exclusively expressed in the stromal vascular fraction of adipose tissue and not in adipocytes. Interestingly, this coregulation is limited to adipose tissue as the expression of RELMα in lung is independent of metabolic regulation. Additionally, we show that resistin and RELMα levels are not subject to regulation by proinflammatory stimuli. Finally, acute hyperglycemia leads to up-regulation of resistin and RELMα transcription in various adipose depots.

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