Abstract

One of the most important threats to global human health is the increasing incidences of metabolic pathologies (including obesity, type 2 diabetes and non-alcoholic fatty liver disease), which is paralleled by increasing consumptions of hypercaloric diets enriched in simple sugars. The challenge is to identify the metabolic pathways affected by the excessive consumption of these dietary components when they are consumed in excess, to unravel the molecular mechanisms leading to metabolic pathologies and identify novel therapeutic targets to manage them. Mechanistic (mammalian) target of rapamycin (mTOR) has emerged as one of the key molecular nodes that integrate extracellular signals, such as energy status and nutrient availability, to trigger cell responses that could lead to the above-mentioned diseases through the regulation of lipid and glucose metabolism. By activating mTOR signalling, excessive consumption of simple sugars (such as fructose and glucose), could modulate hepatic gluconeogenesis, lipogenesis and fatty acid uptake and catabolism and thus lipid deposition in the liver. In the present review we will discuss some of the most recent studies showing the central role of mTOR in the metabolic effects of excessive simple sugar consumption.

Highlights

  • Mechanistic target of rapamycin is a serine/threonine protein kinase that forms the catalytic centre of two multi-protein complexes termed mTORC1 and mTORC2, which have different compositions and responses to upstream signals [1,2]

  • When we compared the effects of glucose and fructose supplementation in female rats, we found that fructose induced hepatic mTOR Ser-2481 phosphorylation to a greater extent than glucose and that only fructose activated downstream effectors of mTORC1 such as phosphorylated 4EBP1 [9]

  • Our results showed that only fructose-supplemented rats displayed significant hyperinsulinemia after seven months of treatment and the lower level of mTORC1 activation observed with the equicaloric glucose supplementation could be attributed, at least in part, to a lack of effect on plasma insulin levels [9]

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Summary

Introduction

Mechanistic (formerly mammalian) target of rapamycin (mTOR) is a serine/threonine protein kinase that forms the catalytic centre of two multi-protein complexes termed mTORC1 and mTORC2, which have different compositions and responses to upstream signals [1,2]. We attributed this effect to the increased plasma adiponectin levels observed only in rats consuming glucose [9], as the liver has been described to be one of the main targets of circulating adiponectin, which activates hepatic AMPK by phosphorylation [23].

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