PAS Kinase: A Nutrient and Energy Sensor “Master Key” in the Response to Fasting/Feeding Conditions

Hurtado-Carneiro, Verónica; Pérez-García, Ana; Álvarez, Elvira; Sanz, Carmen

doi:10.3389/fendo.2020.594053

Cited by 7 publications

(7 citation statements)

References 59 publications

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“…This effect was similar to the one described in the lateral hypothalamic (LH) area [ 21 ], although the exendin-4 effect, in this latter case, was significant only under fasting conditions. Our data suggest that PASK and GLP-1 are performing mutual inter-regulation, and some of the effects of exendin-4 might be mediated by PASK, possibly affecting other liver metabolic sensors and regulators, as several hepatic functions are PASK-dependent [ 18 , 19 , 20 , 24 , 25 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…The PAS domain protein kinase (PASK) has been described as a nutrient sensor involved in the regulation of glucose and energy metabolism homeostasis [ 15 , 16 , 17 , 18 ]. PASK-deficient mice are protected against the development of obesity, insulin resistance, and hepatic steatosis when they are fed with high-fat diets (HFDs) [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent

et al. 2021

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Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent

et al. 2021

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“…The PASK activation model proposes that the interaction of a metabolite with the PAS domain terminates its inhibitory function and transient activation occurs, which will subsequently be stabilized by auto or transphosphorylation and may activate/inhibit various substrates [ 55 , 58 , 60 , 61 ]. In mammals, PASK responds according to nutritional status by contributing to the regulation of glucose homeostasis, energy metabolism, and oxidative stress [ 62 , 63 , 64 , 65 ]. PASK regulates glucagon and insulin secretion [ 66 , 67 ].…”

Section: Nutrient Sensors and Oxidative Stressmentioning

confidence: 99%

Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK

et al. 2021

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The liver’s high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant’s effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.

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“…Like AMPK and mTORC1, it is a nutrient-responsive protein that regulates glucose metabolism and cellular energy, and is also responsive to a variety of intracellular cues, including light, oxygen, and redox state, among many others [24]. In mammals, PASK may be activated by small metabolites, and could regulate glycogen synthesis and protein translation (Figure 1), in addition to being involved in the regulation of glucose homeostasis and energy metabolism [25][26][27], and epigenetics and differentiation [28].…”

Section: Nutrients and Energy Sensors: Importance In Glucose And Energy Homeostasismentioning

confidence: 99%

Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

Hurtado-Carneiro¹,

Pérez-García²,

Álvarez³

et al. 2021

Type 2 Diabetes - From Pathophysiology to Cyber Systems

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Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

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PAS Kinase: A Nutrient and Energy Sensor “Master Key” in the Response to Fasting/Feeding Conditions

Cited by 7 publications

References 59 publications

Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent

Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent

Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK

Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

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