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Early onset and progression of non-alcoholic fatty liver disease in young monosodium l-glutamate-induced obese mice

Published online by Cambridge University Press:  01 June 2018

C. F. F. Coelho ,
L. M. França ,
J. R. Nascimento ,
A. M. dos Santos ,
A. P. S. Azevedo-Santos ,
F. R. F. Nascimento  and
A. M. A. Paes Open the ORCID record for A. M. A. Paes [Opens in a new window]
C. F. F. Coelho
Affiliation:
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, MA, Brazil
L. M. França
Affiliation:
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
J. R. Nascimento
Affiliation:
Laboratory of Immunophysiology, Department of Pathology, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
A. M. dos Santos
Affiliation:
Department of Public Health, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
A. P. S. Azevedo-Santos
Affiliation:
Laboratory of Immunophysiology, Department of Pathology, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
F. R. F. Nascimento
Affiliation:
Laboratory of Immunophysiology, Department of Pathology, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
A. M. A. Paes*
Affiliation:
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, São Luís, MA, Brazil Health Sciences Graduate Program, Federal University of Maranhão, São Luís, MA, Brazil
*
Address for correspondence: A. M. de Andrade Paes, Avenida dos Portugueses, 1966 – Cidade Universitária Dom Delgado, 65080-850 São Luís, MA, Brazil. E-mail: [email protected]
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Abstract

Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.

Keywords

monosodium l-glutamatenon-alcoholic fatty liver diseasenon-alcoholic steatohepatitisobesitymetabolic syndrome
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 2 , April 2019 , pp. 188 - 195
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

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