Abstract

A common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles.

Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress.

Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle. The nuclear factor erythroid 2-related factor 2 (Nrf2) controls adaptive responses and remains the major regulator of quenching mechanisms underlying different types of stress.

Here, we demonstrate a positive role of fasting as a protective mechanism against oxidative stress in skeletal muscle. In particular, by using in vivo and in vitro models of fasting, we found that typical Nrf2-dependent genes, including those controlling iron (e.g., Ho-1) and glutathione (GSH) metabolism (e.g., Gcl, Gsr) are induced along with increased levels of the glutathione peroxidase 4 (Gpx4), a GSH-dependent antioxidant enzyme.

These events are associated with a significant reduction in malondialdehyde, a well-known by-product of lipid peroxidation.

Our results suggest that fasting could be a valuable approach to boost the adaptive anti-oxidant responses in skeletal muscle.

Introduction

Metabolic adaptation responses are essential to preserve energy homeostasis for basic functions in the organism during fasting.

Fasting has a wide range of beneficial effects because it induces protective stress pathways that prevent and/or recover tissue damages; on the contrary, non-physiological, prolonged fasting could be involved in the cell death response governing numerous pathological processes. Fasting has the potential to counter chronic metabolic disorders and improve health and lifespan; by contrast, misguided responses are potentially devastating and can also contribute to diverse types of muscular dysfunctions, like myotonic dystrophy type 1. The skeletal muscle activates selective adaptive programs to low-nutrient availability that are mainly characterized by a rapid decrease in glucose oxidation associated with shifts towards lipid catabolic pathways. To cope with exhausted reservoirs, skeletal muscle also reduces protein synthesis and activates selective forms of autophagy.

This is one of the scientific articles published by one or more synbrAIn collaborators and data scientists.

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