Effect of Fructose and 3,5-Diiodothyronine (3,5-T2) on Lipid Accumulation and Insulin Signalling in Non-Alcoholic Fatty Liver Disease (NAFLD)-Like Rat Primary Hepatocytes

D. Gnocchi; M. Massimi; A. Alisi; S. Incerpi; G. Bruscalupi

doi:10.1055/s-0034-1371858

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2014; 46(05): 333-340
DOI: 10.1055/s-0034-1371858

Endocrine Research

Effect of Fructose and 3,5-Diiodothyronine (3,5-T₂) on Lipid Accumulation and Insulin Signalling in Non-Alcoholic Fatty Liver Disease (NAFLD)-Like Rat Primary Hepatocytes

D. Gnocchi

¹Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, Rome, Italy

,

M. Massimi

²Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

,

A. Alisi

³Liver Research Unit and Hepato-Metabolic Disease Unit, “Bambino Gesù” Children’s Hospital, IRCCS, Rome, Italy

,

S. Incerpi

⁴Department of Sciences, University Roma Tre, Rome, Italy

,

G. Bruscalupi

¹Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, Rome, Italy

› Author Affiliations

Abstract

Non-alcoholic fatty liver disease (NAFLD) is nowadays considered as one of the most serious pathological conditions affecting the liver. NAFLD is supposed to be initiated by the accumulation of lipids in the liver, which finally results in an impaired hepatic insulin signalling. Many researchers have recently focused their attention on the role played by fructose as a NAFLD-triggering agent, because of the increased diffusion of fructose-sweetened food. However, epidemiological data do not permit to evaluate the role of fructose per se, because these foods are often associated with elevated energy intake and unhealthy lifestyle. In the present work, we analysed the effects of fructose on the accumulation of lipids and insulin signalling in rat primary hepatocytes. Moreover, we investigated the effect of the thyroid hormone metabolite, devoid of thyrotoxic effects, 3,5-diiodothyronine (3,5-T₂) over the same parameters. To evaluate the effect on insulin signalling we took into consideration three key proteins, such as p85 subunit of phosphatidylinositol 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), and Akt. Our results show that fructose in vitro, in the range of physiological concentrations, was not able to stimulate either lipid accumulation or to impair insulin signalling in our NAFLD-like rat primary hepatocytes. Our data thus support the idea that fructose per se may exert detrimental effects mainly triggering systemic effects, rather than directly affecting isolated hepatocytes. Moreover, we demonstrated that 3,5-T₂, at physiological levels, reduces lipid content and triggers phosphorylation of Akt in an insulin receptor-independent manner, revealing new interesting properties as a biologically active molecule.

Key words

insulin signal transduction - Akt - p85 - PTEN

Full Text

References

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