Glycation impairs hepatic lipid metabolism and glucose tolerance in high-fat diet-induced obese rats, contributing to the onset of NAFLD

Objectives: Non-alcoholic fatty liver disease (NAFLD) is an insulin resistance- and lipotoxicity-related condition. We evaluated the role of glycation, often present without overt hyperglycaemia like in prediabetes and obesity1, in the dysregulation of hepatic lipid metabolism and in the induction of glucose dysmetabolism. Methods: An animal model of high-triglyceride diet-induced obesity (HFD), methylglyoxal (MG)-induced glycation (MG) or both (HFDMG) was used to asses liver lipid species in vivo by 1H nuclear magnetic resonance spectroscopy (MRS) and ex vivo by mass spectrometry (MS) and gas chromatography (GC), followed by western blotting and histologic analysis (n=6/group). Results: Although the high-fat diet increased liver fat mass in the MRS, only MG supplementation decreased unsaturated lipids, esterification and triglyceride levels (MRS and MS). HFDMG group also had decreased levels of plasmalogens (antioxidant phospholipids) and cardiolipins (mitochondrial phospholipids) in MS and GC analysis. Moreover, when combined to the high-fat diet glycation decreased insulin signalling and upregulated de novo fatty acid synthesis pathways. Conclusions: Although the high-fat diet alone increased liver fat fraction, only the association with glycation changed lipid metabolism, contributing to the hepatic lipotoxicity observed in NAFLD. Such mechanisms contribute to the vicious circle between insulin resistance, glucose dysmetabolism and NAFLD progression.
Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 2 (2016)