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Post-weaning exposure to high-sucrose diet induces early non-alcoholic fatty liver disease onset and progression in male mice: role of dysfunctional white adipose tissue

Part of: DOHaD Research in Latin-American

Published online by Cambridge University Press:  29 June 2020

Lucas Martins França Open the ORCID record for Lucas Martins França [Opens in a new window] ,
Pâmela Costa dos Santos ,
Wermerson Assunção Barroso ,
Roberta Sabrine Duarte Gondim ,
Caio Fernando Ferreira Coêlho ,
Karla Frida Torres Flister  and
Antonio Marcus de Andrade Paes Open the ORCID record for Antonio Marcus de Andrade Paes [Opens in a new window]
Lucas Martins França
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
Pâmela Costa dos Santos
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
Wermerson Assunção Barroso
Affiliation:
Laboratory of Medical Investigation (LIM-51), Department of Emergency Medicine, School of Medicine, University of São Paulo (FMUSP), São Paulo, SP, Brazil
Roberta Sabrine Duarte Gondim
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
Caio Fernando Ferreira Coêlho
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
Karla Frida Torres Flister
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
Antonio Marcus de Andrade Paes*
Affiliation:
Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, MA, Brazil
*
Address for correspondence: Antonio Marcus de Andrade Paes, Universidade Federal do Maranhão, Departamento de Ciências Fisiológicas, Avenida dos Portugueses, 1966, Campus Dom Delgado, CEP: 65.080-805, São Luís, MA, Brazil. Email: marcuspaes@ufma.br
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) particularly among chronic consumers of added sugar-rich diets. However, the impact of early consumption of such diets on NAFLD onset and progression is unclear. Thus, this study sought to characterise metabolic factors involved in NAFLD progression in young mice fed with a high-sucrose diet (HSD). Male Swiss mice were fed HSD or regular chow (CTR) from weaning for up to 60 or 90 days. Obesity development, glucose homeostasis and serum biochemical parameters were determined at each time-point. At day 90, mice were euthanised and white adipose tissue (WAT) collected for lipolytic function assessment and liver for histology, gene expression and cytokines quantification. At day 60, HSD mice presented increased body mass, hypertriglyceridemia, peripheral insulin resistance (IR) and simple steatosis. Upon 90 days on diet, WAT from HSD mice displayed impaired insulin sensitivity, which coincided with increased fasting levels of glucose and free fatty acids (FFA), as well as NAFLD progression to NASH. Transcriptional levels of lipogenic genes, particularly stearoyl-CoA desaturase-1, were consistently increased, leading to hepatic leukocyte infiltration and pro-inflammatory cytokines spillover. Therefore, our dataset supports IR triggering in the WAT as a major factor for dysfunctional release of FFA towards portal circulation and consequent upregulation of lipogenic genes and hepatic inflammatory onset, which decisively concurred for NAFLD-to-NASH progression in young HSD-fed mice. Notwithstanding, this study forewarns against the early introduction of dietary sugars in infant diet, particularly following breastfeeding cessation.

Keywords

Carbohydrateswhite adipose tissuefree fatty acidslipogenesischildhood
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 5 , October 2020 , pp. 509 - 520
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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