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Aims: Very modest changes in mRNA stability can affect critical points in cellular energy pathways. The aim of this study was to investigate the impact of energy abundant substrates on peroxisome proliferator-activated receptors (PPARs) and PPAR-gamma coactivators (PGCs) mRNA's steady-state levels., Methods: Quantitative RT-PCR study was performed to assess the effect of zero or normal (5 mmol/l) glucose and/or oleic acid (0.3 mmol/l) on mRNA levels of (PPARs) (PGCs) in HepG2 cells., Results: PGC-1alpha mRNA was significantly upregulated in glucose deprived cells (123 % of the control level; p < 0.05), while PGC-1beta mRNA was significantly enhanced in oleate-fed cells (134 % and 160 % of control levels for zero glucose plus oleate and normal glucose plus oleate, respectively; p < 0.05) during the 0.5 h incubation. Upon the 4 h incubation, PPAR-gamma1 and PGC-1alpha mRNAs were significantly elevated in cells lacking glucose (142 % and 163 % of control levels, respectively; p < 0.05). Oleate significantly suppressed PPAR-alpha and PGC-1beta mRNA levels in glucose-deprived cells (58 % and 49 % of control levels, respectively; p < 0.05). PPAR-gamma1 and -gamma2 mRNAs were significantly superinduced when the cells were treated with cycloheximide, whereas PPAR-alpha and PGC-1alpha and-1beta mRNAs were destabilized. Upon actinomycin D treatment, glucose shortage significantly stabilized PPAR-alpha mRNA, while PGC-1alpha mRNA was destabilized by oleate in glucose-deprived cells., Conclusions: Our findings provide evidence that transcriptional processes that are under the control of energetic substrates are interconnected with concurrent translational processes that can change stability of mRNAs.

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver disorders claiming the urgent attention of both medical professionals and the public sphere because of the imminent epidemic of advanced liver injury that appendages epidemic of obesity. Recent research reveals simple triglyceride accumulation in hepatocytes (i.e., liver steatosis) frequently becoming complicated by inflammation (i.e., non-alcoholic steatohepatitis, or NASH) that may progress into more advanced stages of the disease including cirrhosis or, eventually, hepatocellular carcinoma. The exact mechanisms of the progression of NAFLD into overt NASH and advanced disease stages are largely unknown. There is urgent need in terms of both intensive research pursuits and effective practical measures to deal with this common threat.