Effect of Interleukin-15 Receptor Alpha Ablation on the Metabolic Responses to Moderate Exercise Simulated by in vivo Isometric Muscle Contractions

Loro, Emanuele; Jang, Cholsoon; Quinn, William J.; Baur, Joseph A.; Arany, Zoltàn; Khurana, Tejvir S.

doi:10.3389/fphys.2019.01439

Cited by 6 publications

(5 citation statements)

References 60 publications

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“…The “marathon mice” DUhLB have developed a striking metabolic phenotype characterized by accelerated browning of subcutaneous fat and altered mitochondrial biogenesis in response to selection for high treadmill performance [ 29 ]. Likewise, detected RDD candidate genes are involved in the development of brown adipocytes ( Srsf6 [ 93 ]), removal of toxic waste products from lipid metabolism ( Aldh3a2 [ 94 ]), mobilization of fatty acids, mitochondria content and cristae complexity ( Il15r [ 95 ]) and in the regulation of glycolysis associated to obesity and weight gain ( Pfkfb3 [ 96 , 97 ]). Moreover, SV analysis detected a ~2.8 kb inversion in Atp5j whose overexpression has been shown to counteract exercise-induced cardiac hypertrophy in mice [ 98 ].…”

Section: Resultsmentioning

confidence: 99%

Genomic characterization of the world’s longest selection experiment in mouse reveals the complexity of polygenic traits

et al. 2022

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Background Long-term selection experiments are a powerful tool to understand the genetic background of complex traits. The longest of such experiments has been conducted in the Research Institute for Farm Animal Biology (FBN), generating extreme mouse lines with increased fertility, body mass, protein mass and endurance. For >140 generations, these lines have been maintained alongside an unselected control line, representing a valuable resource for understanding the genetic basis of polygenic traits. However, their history and genomes have not been reported in a comprehensive manner yet. Therefore, the aim of this study is to provide a summary of the breeding history and phenotypic traits of these lines along with their genomic characteristics. We further attempt to decipher the effects of the observed line-specific patterns of genetic variation on each of the selected traits. Results Over the course of >140 generations, selection on the control line has given rise to two extremely fertile lines (>20 pups per litter each), two giant growth lines (one lean, one obese) and one long-distance running line. Whole genome sequencing analysis on 25 animals per line revealed line-specific patterns of genetic variation among lines, as well as high levels of homozygosity within lines. This high degree of distinctiveness results from the combined effects of long-term continuous selection, genetic drift, population bottleneck and isolation. Detection of line-specific patterns of genetic differentiation and structural variation revealed multiple candidate genes behind the improvement of the selected traits. Conclusions The genomes of the Dummerstorf trait-selected mouse lines display distinct patterns of genomic variation harbouring multiple trait-relevant genes. Low levels of within-line genetic diversity indicate that many of the beneficial alleles have arrived to fixation alongside with neutral alleles. This study represents the first step in deciphering the influence of selection and neutral evolutionary forces on the genomes of these extreme mouse lines and depicts the genetic complexity underlying polygenic traits.

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Section: Resultsmentioning

confidence: 99%

Genomic characterization of the world’s longest selection experiment in mouse reveals the complexity of polygenic traits

et al. 2022

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“…The “marathon mice” DUhLB have developed a striking metabolic phenotype characterized by accelerated browning of subcutaneous fat and altered mitochondrial biogenesis in response to selection for high treadmill performance 108 . Likewise, detected RDD candidate genes are involved in the development of brown adipocytes ( Srsf6 109 ), removal of toxic waste products from lipid metabolism ( Aldh3a2 110 ), fatty acids mobilization, mitochondria content, and cristae complexity ( Il15r 111 ) and in the regulation of glycolysis associated to obesity and weight gain ( Pfkfb3 112,113 ). Moreover, SV analysis detected a ~2.8Kb inversion in Atp5j whose overexpression has been shown to counteract exercise-induced cardiac hypertrophy in mice 114 .…”

Section: Resultsmentioning

confidence: 99%

Genomic characterization of world’s longest selection experiment in mouse reveals the complexity of polygenic traits

Palma-Vera

Reyer

Langhammer

et al. 2021

Preprint

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A unique set of mouse outbred lines has been generated through selective breeding in the longest selection experiment ever conducted on mice. Over the course of >140 generations, selection on the control line has given rise to two extremely fertile lines (>20 pups per litter each), two giant growth lines (one lean, one obese) and one long-distance running line. Genomic analysis revealed line-specific patterns of genetic variation among lines and high levels of homozygosity within lines as a result of long-term intensive selection, genetic drift and isolation. Detection of line-specific patterns of genetic differentiation and structural variation revealed multiple candidate genes behind the improvement of the selected traits. We conclude that the genomes of these lines are rich in beneficial alleles for the respective selected traits and represent an invaluable resource for unraveling the polygenic basis of fertility, obesity, muscle growth and endurance fitness.

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“…Bag5 downregulation was induced by catecholamine and contributed to endothelial cell apoptosis (Tan, Asada, & Ge, 2018). Mechanistically, decreased Bag5 induced ER stress, oxidative stress and inflammation response; and these pathological changes may contribute to endothelial cell damage (Honda, He, Wang, & Redington, 2019; Loro et al, 2019). Furthermore, we found that Bag5 downregulation in response to catecholamine treatment was mediated by the inactivation of the MAPK–ERK pathway (Jilg et al, 2019; Thieltges et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

Zhu

Zhao

Chen

et al. 2020

Journal Cellular Physiology

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Bcl-2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine-induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertensionrelated endothelial cell damage. Then, western blots, enzyme-linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholaminetreated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway. Reactivation of the MAPK-ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK-ERK pathway as potential mechanisms underlying catecholamine-induced endothelial cell damage.

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Effect of Interleukin-15 Receptor Alpha Ablation on the Metabolic Responses to Moderate Exercise Simulated by in vivo Isometric Muscle Contractions

Cited by 6 publications

References 60 publications

Genomic characterization of the world’s longest selection experiment in mouse reveals the complexity of polygenic traits

Genomic characterization of the world’s longest selection experiment in mouse reveals the complexity of polygenic traits

Genomic characterization of world’s longest selection experiment in mouse reveals the complexity of polygenic traits

Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

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