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Interplay between gut microbiota and p66Shc affects obesity‐associated insulin resistance
Author(s) -
Ciciliot Stefano,
Albiero Mattia,
Campanaro Stefano,
Ponciicol,
Tedesco Serena,
Scattolini Valentina,
Dalla Costa Francesca,
Cignarella Andrea,
Vettore Monica,
Maria Di Gangi Iole,
Bogialli Sara,
Avogaro Angelo,
Paolo Fadini Gian
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701409r
Subject(s) - insulin resistance , gut flora , biology , intestinal permeability , endocrinology , phenotype , microbiome , islet , medicine , obesity , insulin , gene , biochemistry , genetics , immunology
The 66 kDa isoform of the mammalian She 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 g ( 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. FASEB J. 32, 4004–4015 (2018). www.fasebj.org