Interplay between gut microbiota and p66Shc affects obesity‐associated insulin resistance
| Autor: | Stefano Campanaro, Iole Maria Di Gangi, Francesca Dalla Costa, Angelo Avogaro, Gian Paolo Fadini, Mattia Albiero, Andrea Cignarella, Nicol Poncina, Valentina Scattolini, Serena Tedesco, Stefano Ciciliot, Sara Bogialli, Monica Vettore |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
gut bacteria
Male 0301 basic medicine medicine.medical_specialty Src Homology 2 Domain-Containing Transforming Protein 1 Branched-chain amino acid microbiome Pancreatitis-Associated Proteins Inflammation Biology Gut flora Diet High-Fat Biochemistry metabolic syndrome Mice 03 medical and health sciences chemistry.chemical_compound Insulin resistance Internal medicine Gene expression Genetics medicine oxidative stress Animals Obesity Molecular Biology biology.organism_classification medicine.disease REG3G Gastrointestinal Microbiome Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry inflammation Adipogenesis Female Insulin Resistance medicine.symptom Metabolic syndrome Gene Deletion Biotechnology |
| Zdroj: | The FASEB Journal. 32:4004-4015 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201701409r |
| Popis: | The 66 kDa isoform of the mammalian Shc gene promotes adipogenesis, and p66Shc-/- mice accumulate less body weight than wild-type (WT) mice. As the metabolic consequences of the leaner phenotype of p66Shc-/- mice is debated, we hypothesized that gut microbiota may be involved. We confirmed that p66Shc-/- mice gained less weight than WT mice when on a high-fat diet (HFD), but they were not protected from insulin resistance and glucose intolerance. p66Shc deletion significantly modified the composition of gut microbiota and their modification after an HFD. This was associated with changes in gene expression of Il-1b and regenerating islet-derived protein 3 γ ( Reg3g) in the gut and in systemic trimethylamine N-oxide and branched chain amino acid levels, despite there being no difference in intestinal structure and permeability. Depleting gut microbiota at the end of HFD rendered both strains more glucose tolerant but improved insulin sensitivity only in p66Shc-/- mice. Microbiota-depleted WT mice cohoused with microbiota-competent p66Shc-/- mice became significantly more insulin resistant than WT mice cohoused with WT mice, despite no difference in weight gain. These findings reconcile previous inconsistent observations on the metabolic phenotype of p66Shc-/- mice and illustrate the complex microbiome-host-genotype interplay under metabolic stress.-Ciciliot, S., Albiero, M., Campanaro, S., Poncina, N., Tedesco, S., Scattolini, V., Dalla Costa, F., Cignarella, A., Vettore, M., Di Gangi, I. M., Bogialli, S., Avogaro, A., Fadini, G. P. Interplay between gut microbiota and p66Shc affects obesity-associated insulin resistance. |
| Databáze: | OpenAIRE |
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