FATTY LIVER AND INSULIN RESISTANCE: TIME COURSE APPEARANCE OF THE CHANGES INDUCED BY A FRUCTOSE RICH DIET

MASSA ML; BLAIOTTA C; CASTRO MC; GAGLIARDINO JJ; FRANCINI F

Berlin

Congreso; 48th Annual Meeting of EASD; 2012

The European Association for the Study of Diabetes

Background and aims: we have previously shown that administration of fructose to normal rats during 3 weeks induced insulin resistance, impaired glucose tolerance, fatty liver and hepatic carbohydrate metabolism abnormalities. The aim of this study was to evaluate the time-course of development of these alterations triggered by a fructose rich diet (FRD). Materials and methods: for this purpose we fed normal male Wistar rats for 7, 14 and 21 days with a) a standard commercial diet (C) and b) a C diet plus 10% fructose in the drinking water (DRF). At each time we measured glycemia (G), triglyceridemia (TG) and insulinemia (I). HOMA-IR, HOMA-â and Index for hepatic sensitivity to insulin (IHIS) ratios were calculated. In liver we measured a) protein carbonyl groups and reduced glutathione (GSH) as oxidative stress markers (OSM), b) liver glycogen and triglyceride content, c) glucokinase (GK), glucose-6-phosphatase (G-6-Pase) and glucose-6-phosphate dehydrogenase (G-6-P DH) activities and d) SREBP-1c, fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT), G-6-Pase and G-6-P DH gene expression.   Results: (*p<0.05 vs.C)   C1 FRD1 C2 FRD2 C3 FRD3 In (ng/ml) 0,5±0,07 0,6±0,06 0,6±0,06 0,7±0,06 0,6±0,04 1,1±0,2* G (mg/dl) 115±3 118±4 103±3 121±6 117±2 117±3 TG (mg/dl) 103±6 134±11* 112±15 172±15* 102±11 226±31* IHIS (k/GPA x InPA) 5,07±0,9 4,12±0,4 4,72±0,7 3,44±0,3 4,15±0,26 2,26±0,3* HOMA IR 3,8±0,5 4,9±0,4 3,9±0,3 5,2±0,5* 4,6±0,3 8,1±1,2* HOMA â 39,4±5 47,2±5,2 45,8±5,3 53,5±5,2 48,5±3,5 78,5±11,6* GK (mU/mg prot) 10±0,5 12±0,4* 9±0,8 16±1* 9±0,6 19±1* G6Pase (latency %) 8±2 13±3 8±1 18±2* 7±1 15±1* Glycogen (µg/mg tis) 7,0±0,4 7,4±0,3 6,8±0,4 8,2±0,2* 8,4±0,3 10,8±0,4* Liver TG (µg/100 mg tis) 304±13 470±59* 277±30 376±30 301±25 469±17* Enhanced expression of all genes was recorded after one week. Carbonyl content was increased and GSH was reduced at two weeks treatment. . Conclusion: increased serum and liver content of TG were the earliest changes induced by fructose administration while OSM and other liver dysfunctions appeared on the second week while enhanced HOMA â and hyperinsulinemia (â cell reaction) were the latest change recorded suggesting that would be the consequence of metabolic and OS occurred in liver and probably adipose tissue as well.   This study was partially supported by grants from CONICET to Massa ML (PIP 2011-0371) and Universidad Nacional de La Plata, Argentina.