Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration

Anderson C Marçal1, Mauro Leonelli, Jarlei Fiamoncini

  • 1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP), SP, Brazil. acmarcal@yahoo.com.br

Insights

High-fat diets induce insulin resistance, leading to changes in nitric oxide synthase (NOS) and retinal damage. This study in obese rats reveals thinner retinal layers and increased apoptosis, suggesting a link between diet, metabolic syndrome, and retinopathy.

Area of Science:

  • Ophthalmology
  • Metabolic Science
  • Molecular Biology

Background:

  • Diabetic retinopathy is linked to nitric oxide (NO) imbalance, regulated by nitric oxide synthase (NOS).
  • The insulin receptor substrate (IRS)/PI3K/AKT pathway and NOS isoforms may be involved in retinopathy development.
  • Insulin resistance is a key factor in metabolic syndrome and type 2 diabetes.

Purpose of the Study:

  • To investigate the impact of high-fat diet (HFD)-induced insulin resistance on retinal morphology and apoptosis.
  • To analyze changes in key signaling pathways and NOS isoform expression in the retina of HFD-fed rats.
  • To explore the relationship between HFD, insulin resistance, and retinopathy.

Main Methods:

  • Induction of insulin resistance in obese rats using a high-fat diet (HFD).
  • Morphological and apoptosis index analysis of retinal tissues.
  • Immunoblotting to quantify protein levels of AKT(1), eNOS, and nNOS.
  • Immunohistochemistry to assess iNOS and 4-hydroxynonenal levels and apoptotic nuclei count.

Main Results:

  • HFD rats showed decreased levels of AKT(1), eNOS, and nNOS proteins in retinal tissue.
  • Increased levels of iNOS and 4-hydroxynonenal were observed in HFD rats.
  • HFD rats exhibited a higher number of apoptotic nuclei and thinner inner and outer retinal layers compared to controls.

Conclusions:

  • HFD-induced insulin resistance alters retinal pathways, affecting NOS expression and leading to retinal damage and apoptosis.
  • Retinopathy may develop through direct effects of dietary fatty acids or insulin-resistance-mediated intracellular pathway changes.
  • This HFD-induced insulin resistance rat model is valuable for studying retinopathy in the context of metabolic syndrome and type 2 diabetes.

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