Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner

Maddison, Lisette A.; Joest, Kaitlin E.; Kammeyer, Ryan; Chen, Wenbiao

doi:10.1152/ajpendo.00441.2014

Cited by 49 publications

(61 citation statements)

References 40 publications

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“…In addition, variants of upstream, downstream, and intronic regions of the immunoglobulin heavy chain variable ( IGHV ) gene were annotated. Interesting, this gene has been reported to be the most important indicator of chronic lymphocytic leukemia prognosis48. Although the tambaqui genome sequences are still not available, comparative genome analysis enabled the identification of large number of markers in genic regions, which in turn could be used in tambaqui breeding programs.…”

Section: Discussionmentioning

confidence: 99%

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

Nunes

Liu

Pértille

et al. 2017

Sci Rep

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Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs.

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Section: Discussionmentioning

confidence: 99%

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

Nunes

Liu

Pértille

et al. 2017

Sci Rep

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“…Similar to mouse models, diet induced obesity in the zebrafish increases serum triglycerides and hepatic lipid accumulation 12 . Furthermore, overfed zebrafish have elevated fasting glucose, suggesting glucose intolerance 14 . Using the assay described here we have shown that 24 hr of pretreatment with Metformin, an insulin sensitizer, increases the metabolic rate response to insulin treatment 5 .…”

Section: Discussionmentioning

confidence: 99%

High Throughput <em>Danio Rerio</em> Energy Expenditure Assay

Williams

Renquist

2016

JoVE

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Zebrafish are an important model organism with inherent advantages that have the potential to make zebrafish a widely applied model for the study of energy homeostasis and obesity. The small size of zebrafish allows for assays on embryos to be conducted in a 96-or 384-well plate format, Morpholino and CRISPR based technologies promote ease of genetic manipulation, and drug treatment by bath application is viable. Moreover, zebrafish are ideal for forward genetic screens allowing for novel gene discovery. Given the relative novelty of zebrafish as a model for obesity, it is necessary to develop tools that fully exploit these benefits. Herein, we describe a method to measure energy expenditure in thousands of embryonic zebrafish simultaneously. We have developed a whole animal microplate platform in which we use 96-well plates to isolate individual fish and we assess cumulative NADH 2 production using the commercially available cell culture viability reagent alamarBlue. In poikilotherms the relationship between NADH 2 production and energy expenditure is tightly linked. This energy expenditure assay creates the potential to rapidly screen pharmacological or genetic manipulations that directly alter energy expenditure or alter the response to an applied drug (e.g. insulin sensitizers). Video LinkThe video component of this article can be found at

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“…Akt signaling plays a central role in insulin-stimulated glucose uptake in peripheral tissues in both mammals and zebrafish 43,44 ; therefore, we examined if insulin-mediated Akt phosphorylation was affected by genetic deletion of gpr27. Akt signaling plays a central role in insulin-stimulated glucose uptake in peripheral tissues in both mammals and zebrafish 43,44 ; therefore, we examined if insulin-mediated Akt phosphorylation was affected by genetic deletion of gpr27.…”

Section: Loss Of Gpr27 Abrogates Akt-dependent Insulin Signalingmentioning

confidence: 99%

“…We next sought to determine if there was a defect in insulin signaling in gpr27 KO zebrafish. Akt signaling plays a central role in insulin-stimulated glucose uptake in peripheral tissues in both mammals and zebrafish 43,44 ; therefore, we examined if insulin-mediated Akt phosphorylation was affected by genetic deletion of gpr27. Following a 2-h incubation period, lysates were generated and subjected to Western blotting for p-Akt (Ser473) and total Akt ( Figure 4D-E).…”

Section: Loss Of Gpr27 Abrogates Akt-dependent Insulin Signalingmentioning

confidence: 99%

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

Nath

Chen

et al. 2019

FASEB j.

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G protein-coupled receptors (GPCRs) comprise the largest group of membrane receptors in eukaryotic genomes and collectively they regulate nearly all cellular processes.Despite the widely recognized importance of this class of proteins, many GPCRs remain understudied. G protein-coupled receptor 27 (Gpr27) is an orphan GPCR that displays high conservation during vertebrate evolution. Although, GPR27 is known to be expressed in tissues that regulate metabolism including the pancreas, skeletal muscle, and adipose tissue, its functions are poorly characterized. Therefore, to investigate the potential roles of Gpr27 in energy metabolism, we generated a whole body gpr27 knockout zebrafish line. Loss of gpr27 potentiated the elevation in glucose levels induced by pharmacological or nutritional perturbations. We next leveraged a mass spectrometry metabolite profiling platform to identify other potential metabolic functions of Gpr27. Notably, genetic deletion of gpr27 elevated medium-chain acylcarnitines, in particular C6-hexanoylcarnitine, C8-octanoylcarnitine, C9-nonanoylcarnitine, and C10-decanoylcarnitine, lipid species known to be associated with insulin resistance in humans. Concordantly, gpr27 deletion in zebrafish abrogated insulin-dependent Akt phosphorylation and glucose utilization. Finally, loss of gpr27 increased the expression of key enzymes in carnitine shuttle complex, in particular the homolog to the brain-specific isoform of CPT1C which functions as a hypothalamic energy senor. In summary, our findings shed light on the biochemical functions of Gpr27 by illuminating its role in lipid metabolism, insulin signaling, and glucose homeostasis. K E Y W O R D Scarnitine palmitoyltransferase I, G protein-coupled receptors, insulin resistance, lipid metabolism, metabolomic profiling * SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Nath AK, Ma J, Chen Z-Z, et al. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. The FASEB Journal.

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Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner

Abstract: Maddison LA, Joest KE, Kammeyer RM, Chen W. Skeletal muscle insulin resistance in zebrafish induces alterations in ␤-cell number and glucose tolerance in an age-and diet-dependent manner.

Cited by 49 publications

References 40 publications

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

High Throughput <em>Danio Rerio</em> Energy Expenditure Assay

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

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