CHOLINE DEPRIVATION ALTERS THE EXPRESSION OF MATRIX METALLOPROTEINASES (MMPs) IN THE LIVER OF STREPTOZOTOCIN (STZ) -INDUCED DIABETIC RATS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 818-841-Diabetes Pathophysiology & Complications
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-830
Charis Liapi*1, Argyro Kyriakaki1, Athina Strilakou1, Hussam Al-Humadi1, Evangelos Fragkoulis1, Nikolaos Tentolouris1, Maria Gazouli2 and Nikolaos Anagnou2
1Medical School University of Athens, Greece, 2Athens Medical School, Athens, Greece
Introduction

Choline is B12 vitamin co-factor and has an augmentable clinical interest since it takes part in vital physiological functions of the organism. Choline deprivation is a well studied model of nonalcoholic liver steatosis observed in common pathological (alcoholism, malnutrition) or physiological states (pregnancy, lactation). Hepatocellular modifications have also been shown in diabetes mellitus. Liver damage is associated with extracellular matrix degradation; matrix metalloproteinases (MMPs) play a central role in this procedure. MMPs have shown increase in several diseases and are strictly regulated.   

Aim

The aim of the study was to investigate the effect of dietary choline deprivation on liver MMP-2 and MMP-9 gene expression in adult-onset STZ–induced diabetic rats.

Methods

Male adult Wistar rats (N=48) were divided in four groups: control (C), choline-deprived (CD), diabetic (D) and choline-deprived diabetic (D+CD). Rats were killed at 30 days (groups C1, CD1, D1, D1+CD1) and 60 days (groups C2, CD2, D2, D2+CD2). MMPs gene expression was determined by Reverse Trascriptase RT–PCR in the rat liver samples.  

Results

MMP-2 gene expression was found significantly increased in groups CD1 (+53%, p<0.01), D1 (+47%, p<0.05) and D1+CD1 (+41%, p<0.05) at 30 days and only in CD2 (+60%, p<0.001) at 60 days compared to control. MMP-2 expression was significantly decreased in the D2+CD2 group compared to CD2 (-41%, p<0.001). MMP-9 gene expression was found significantly increased in groups CD1 (+94%, p<0.001), D1 (+28%, p<0.001) and D1+CD1 (+36%, p<0.001) at one month and only in group CD2 (+90%, p<0.001) at two months. MMP-9 expression was significantly decreased in D1+CD1 and D2+CD2 groups compared to CD1 and CD2 groups respectively (-30% and -43% respectively). Non-significant alterations were noticed between D2 and D2+CD2 groups.

Conclusion

MMP-2 and MMP-9 gene expression in adult rat liver is enhanced either in diabetes or choline deficiency alone or when both settings are present. It seems possible that choline-deficiency induced oxidative stress and the consequent impaired liver function could be involved in the development of diabetes by impairing probably the glucagon metabolism. Furthermore, the observed down-regulation of MMPs in D+CD groups compared to D groups could imply severe degeneration of the extracellular matrix modulating also the progress of diabetes. Further studies are in progress in order to elucidate the underlying mechanisms.

Nothing to Disclose: CL, AK, AS, HA, EF, NT, MG, NA

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