Scientists map out how prolonged exercise and fasting cause acute liver metabolic regulation

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In a recent study titled ‘PGC-1α in exercise and fasting-induced regulation of hepatic UPR in mice’ published by the Pflügers Archiv - European Journal of Physiology, researchers have discovered that prolonged exercise and fasting cause endoplasmic reticulum (ER) stress and autophagy in the liver without the need for transcriptional coactivator peroxisome proliferator activated receptor-gamma coactivator 1alpha (PGC- 1α).

Exercise and fasting have been long known to regulate metabolism especially in the liver.  This include regulation of glucose homeostasis through the enhanced glycogenolysis and gluconeogenesis within liver cells.  Scientific evidence shows that the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, and their enzymatic activity significantly increase during exercising. It has also been established that prolonged exercise and fasting impose metabolic challenges characterized by endoplasmic reticulum stress and autophagy in the liver. This ER stress characterized by hepatic Unfolded protein response (UPR) is an attempt to revert to normal homeostasis after the challenges imposed by exercise and fasting.

To determine if PGC-1α is involved in the regulation of hepatic UPR and autophagy in response to both exercise and fasting in mice, researchers including Henriette Pilegaard of Department of Biology, University of Copenhagen in Denmark conducted a study using liver-specific PGC-1α knockout mice. From the liver and plasma samples of the fasted mice and 1-hour treadmill-exercised mice, they determined the hepatic eIF2α phosphorylation, citrate synthase (CS) and hepatic L-3- hydroxy-CoA dehydrogenase (HAD) activity. Real time PCR was used to determine the hepatic mRNA content of selected genes such as sXBP1.

From their study, Pilegaard and Co-researchers found out that fasting reduced hepatic IRE1α phosphorylation and protein content as well as PERK protein and sXBP1 mRNA content as opposed to exercising where an increase was rather observed. In this regard, it was evident that exercising and fasting regulates liver metabolism differently. While fasting induce downregulation of the UPR, exercising on the other hand induced the activation of UPR. Having collated all the results, the researchers concluded that PGC-1α may not be necessarily needed for the fasting and exercise-induced regulation of UPR and autophagy.

Read full study here: https://rdcu.be/7B7u

Reference: Kristensen C.M, Olsen M.A, Jessen H, Brandt N, Meldgaard J.N & Pilegaard H. PGC-1α in exercise and fasting-induced regulation of hepatic UPR in mice. Pflügers Archiv - European Journal of Physiology (2018) 470:1431–1447.

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