Role of PPARα in Hepatic Carbohydrate Metabolism.
- Authors
- Peeters, Annelies; Baes, Myriam
- Year
- 2010
- Journal
- PPAR research
- PMID
- 20936117
- DOI
- 10.1155/2010/572405
- PMCID
- PMC2948921
Tight control of storage and synthesis of glucose during nutritional transitions is essential to maintain blood glucose levels, a process in which the liver has a central role. PPARα is the master regulator of lipid metabolism during fasting, but evidence is emerging for a role of PPARα in balancing glucose homeostasis as well. By using PPARα ligands and PPARα(-/-) mice, several crucial genes were shown to be regulated by PPARα in a direct or indirect way. We here review recent evidence that PPARα contributes to the adaptation of hepatic carbohydrate metabolism during the fed-to-fasted or fasted-to-fed transition in rodents.
Influence of insulin and PPARα on carbohydrate metabolic pathways. Different fates and different sources of hepatic G6P are depicted, together with the regulatory effects of PPARα. FA: fatty acids; FAO: fatty acid oxidation; G6P: glucose-6-phosphate; OXPHOS: oxidative phosphorylation; TCA: tricyclic acid cycle.
LLM interpretation
This is a metabolic pathway diagram illustrating the regulatory effects of insulin and PPARα on hepatic glucose-6-phosphate (G6P) metabolism under "FED" and "Fasted" conditions. In the FED state, insulin is shown to promote glucokinase, glycolysis, and *de novo* fatty acid synthesis while inhibiting gluconeogenesis. In the Fasted state, PPARα is shown to promote fatty acid oxidation (FAO), gluconeogenesis, and ketone body production while inhibiting glycolysis and glycogenolysis.
Influence of PPARα on hepatic glycolysis and gluconeogenesis. The different fates of glycolytic products and gluconeogenic precursors are depicted, together with the regulatory effects of PPARα. Blue arrows show breakdown of glucose via glycolysis, PPP and TCA cycle; purple arrows indicate gluconeogenic steps. Genes which were proven to be directly regulated by PPARα are presented as a full green arrow. Stimulatory effects which were only proven by treatment with PPARα ligands are shown as a dashed bright green arrow. An effect that was only observed in PPARα −/− mice is depicted as a dark green dashed arrow. Genes in which a PPRE was identified, but no in vivo activation by PPARα was observed are presented with a dark green dotted arrow. Genes which were only suggested to be stimulated by PPARα are indicated with a grey dotted arrow. A suppressive effect of PPARα is shown with a red mark. 6PDGH: 6-phosphogluconate dehydrogenase; ALT: alanine transaminase; AQP: aquaporin; FDP: fructose-di-phosphatase; G6Pase: glucose-6-phosphatase; G6PDH: glucose-6-phosphate dehydrogenase; GLUT2: glucose transporter 2; cGPDH: cytosolic glycerol 3-phosphate dehydrogenase; MCT: monocarboxylate transporter; mGPDH: mitochondrial glycerol 3-phosphate dehydrogenase; LDH: lactate dehydrogenase; PC: pyruvate carboxylase; PDH: pyruvate dehydrogenase; PDK4: pyruvate dehydrogenase kinase 4; PEPCK: phosphoenolpyruvate kinase; PFK: phosphofructokinase; Taldo1: transaldolase 1; TCA: tricyclic acid cycle.
LLM interpretation
This figure is a metabolic pathway diagram illustrating the regulatory influence of PPARα on hepatic glycolysis and gluconeogenesis. Blue and purple arrows map the flow of glucose through glycolysis, the pentose phosphate pathway, and gluconeogenesis, while various green and grey arrows indicate stimulatory effects of PPARα on specific genes (e.g., PEPCK, PDK4, G6Pase). Red markers denote suppressive effects, such as the inhibition of pyruvate kinase by PPARα.
Influence of PPARα on hepatic glycogen metabolism. Synthesis (blue arrows) and breakdown of glycogen (purple arrows) are depicted, together with the regulatory effects of PPARα. Direct transcriptional influence is presented as a full green arrow. An effect that was only observed in PPARα −/− mice is depicted as a dark green dashed arrow. Genes in which a PPRE was identified, but no in vivo activation by PPARα was observed are presented with a dark green dotted arrow. A suppressive effect of PPARα is shown with a red mark. G6Pase: glucose-6-phosphatase; GLUT2: glucose transporter 2; GSK-3β: glycogen synthase kinase 3β; UDP-glucose: uridine diphosphate glucose.
LLM interpretation
This is a schematic diagram illustrating the regulatory influence of PPARα on hepatic glycogen synthesis and breakdown. The figure maps the biochemical pathway from blood glucose through GLUT2 to glycogen, highlighting the roles of enzymes such as Glucokinase, G6Pase, Glycogen synthase, and Glycogen phosphorylase. PPARα is shown to have various effects, including direct transcriptional activation (green arrow), suppression (red line), and specific regulatory patterns observed in PPARα −/− mice (dashed and dotted green arrows).
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