Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Metabolic exhaustion underlies sarcopenic obesity susceptibility in aging mice as revealed by multi-omics factor analysis

ABSTRACT: Sarcopenic obesity affects up to 40% of older adults with obesity, yet many remain protected despite comparable metabolic burden. The molecular basis for this heterogeneity remains unknown, limiting risk stratification and targeted intervention. We superimposed metabolic challenge on aging physiology by exposing seventy-two 12-month-old female mice to high-fat diet (HFD) or standard diet for 7 months, modeling the development of sarcopenic obesity during the transition from middle to old age. Multi-Omics Factor Analysis (MOFA) integrated muscle transcriptomics and metabolomics to identify latent factors explaining phenotypic variation. Total RNA was quantified using the Qubit 4.0 fluorimetric Assay (Thermo Fisher Scientific). Libraries were prepared from 125 ng of total RNA using the NEGEDIA Digital mRNA-seq research grade sequencing service v2.0 (Next Generation Diagnostic S.r.l., Pozzuoli, Italy), which included library preparation, quality assessment and sequencing on a NovaSeq 6000 sequencing system using a single-end, 100 cycle strategy (Illumina Inc.). Raw data were analyzed by Next Generation Diagnostic srl proprietary NEGEDIA Digital mRNA-seq pipeline (Next Generation Diagnostic S.r.l., Pozzuoli, Italy, v2.0), which involves a cleaning step by quality filtering and trimming, alignment to the reference genome and counting by gene

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Rossella De Cegli

PROVIDER: E-MTAB-15944 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Over the past decades, Helicoverpa armigera nucleopolyhedrovirus (HearNPV) has been widely used for biocontrol of cotton bollworm, which is one of the most destructive pest insects in agriculture worldwide. However, the molecular mechanism underlying the interaction between HearNPV and host insects remains poorly understood. In this study, high throughput RNA-sequencing was integrated with label-free quantitative proteomics analysis to examine the dynamics of gene expression in the fat body of H. armigera larvae in response to challenge with HearNPV. RNA-sequencing-based transcriptomic analysis indicated that host gene expression was substantially altered, yielding 3,850 differentially expressed genes (DEGs), while no global transcriptional shut-off effects were observed in the fat body. Among the DEGs, 60 immunity-related genes were down-regulated after baculovirus infection, a finding that was consistent with the results of quantitative real-time RT-PCR (qRT-PCR). Gene ontology and functional classification demonstrated that the majority of down-regulated genes were enriched in gene cohorts involved in energy, carbohydrate, and amino acid metabolic pathways. Proteomics analysis identified differentially expressed proteins in the fat body, among which 76 were up-regulated, whereas 373 were significantly down-regulated upon infection. The down-regulated proteins are involved in metabolic pathways such as energy metabolism, carbohydrate metabolism (CM), and amino acid metabolism, in agreement with the RNA-seq data. Furthermore, correlation analysis suggested a strong association between the mRNA level and protein abundance in the H. armigera fat body. More importantly, the predicted gene interaction network indicated that a large subset of metabolic networks was significantly negatively regulated by viral infection, including CM-related enzymes such as aldolase, enolase, malate dehydrogenase and triose-phosphate isomerase. Taken together, transcriptomic combined with proteomic data elucidated that baculovirus established systemic infection of host larvae, and manipulated the host mainly by suppressing the host immune response and down-regulating metabolism to allow viral self-replication and proliferation. Therefore, this study provided important insights into the mechanism of host-baculovirus interaction.

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Metabolic exhaustion underlies sarcopenic obesity susceptibility in aging mice as revealed by multi-omics factor analysis

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