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Insulin Injection and Hemolymph Extraction to Measure Insulin Sensitivity in Adult Drosophila melanogaster
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Microbiota determines insulin sensitivity in TLR2-KO mice.

Dioze Guadagnini1, Guilherme Zweig Rocha1, Andrey Santos1

  • 1Department of Internal Medicine-FCM, University of Campinas-UNICAMP, Campinas, SP, Brazil.

Life Sciences
|August 30, 2019
PubMed
Summary

Gut microbiota influences metabolic syndrome. In this study, TLR2 knockout mice developed insulin resistance and obesity due to altered gut bacteria, demonstrating microbiota

Keywords:
Genetic protectionGut microbiotaInsulin resistanceLPSTLR2

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Area of Science:

  • Microbiology
  • Immunology
  • Metabolic Syndrome

Background:

  • Environmental factors significantly impact gut microbiota composition and obesity development.
  • Toll-like receptor 2 knockout (TLR2-/-) mice are typically protected from diet-induced insulin resistance in certain housing conditions.
  • However, in the study's specific housing conditions, TLR2-/- mice did not exhibit this protective phenotype.

Purpose of the Study:

  • To investigate how specific animal housing conditions influence gut microbiota.
  • To assess the impact of these conditions on glucose tolerance and insulin sensitivity in TLR2-/- mice.
  • To elucidate the mechanisms underlying insulin resistance in this model.

Main Methods:

  • Gut microbiota analysis using metagenomics.
  • Assessment of glucose tolerance via glucose tolerance tests (GTT).
  • Insulin sensitivity evaluation using hyperinsulinemic euglycemic clamps and insulin signaling analysis via immunoblotting.

Main Results:

  • TLR2-/- mice under study conditions developed metabolic syndrome, including insulin resistance, glucose intolerance, and weight gain.
  • Significant alterations in gut microbiota were observed in TLR2-/- mice, with decreased Proteobacteria and Bacteroidetes, and increased Firmicutes, Oscillospira, and Ruminococcus.
  • Increased circulating LPS, subclinical inflammation, TLR4 activation, ER stress, and JNK activation were linked to insulin resistance.

Conclusions:

  • Intestinal microbiota can induce insulin resistance and obesity.
  • This occurs even in animal models genetically predisposed to protection against these conditions.
  • The findings highlight the critical role of gut microbiota in metabolic health and disease.