Abstract
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. 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. 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. 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.
Highlights
Living organisms must continuously adapt their energy metabolism to a discontinuous supply of nutrients
Using quantitative real-time RT-PCR we first studied the effects of 0.5 h and 4 h incubations with zero or normal (5 mmol/l) concentrations of glucose and/or oleic acid (0.3 mmol/l) on mRNA expression of several molecular species functionally allied to peroxisome proliferator-activated receptors (PPAR) transcriptional factors in HepG2 cells
Relative mRNA levels of PPAR-α, -γ1, -γ2, and PGC-1α and -1β determined in duplicate assays from three independent experiments were compared to the control mRNA levels of the same molecules when cells were maintained under normal glucose without oleate during the early incubation period
Summary
Living organisms must continuously adapt their energy metabolism to a discontinuous supply of nutrients. The liver plays a key role in the maintenance of systemic energetic homeostasis. During a medium- to long-term fast, gluconeogenesis is turned on to maintain appropriate blood glucose levels. Adipose tissue acts with the liver to ensure glucose homeostasis during the postabsorptive period. Fatty acid oxidation is activated, providing energy for tissues and, in the liver, for the gluconeogenic process. Ketone bodies are exported from the liver providing an alternative fuel source to glucose. According to the conventional view, systemic transition from the fed to fasted state is entirely orchestrated by hormones. The hormones mainly elicit these changes by modulating transcription of genes that are involved in glucose and fatty acid metabolism[1]
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