Abstract
The protein kinase with PAS domains (PASK) is a nutrient and energy sensor located in the cells of multiple organs. Many of the recent findings for understanding PASK functions in mammals have been reported in studies involving PASK-deficient mice. This minireview summarizes the PASK role in the control of fasting and feeding responses, focusing especially on the hypothalamus and liver. In 2013, PASK was identified in the hypothalamic areas involved in feeding behavior, and its expression was regulated under fasting/refeeding conditions. Furthermore, it plays a role in coordinating the activation/inactivation of the hypothalamic energy sensors AMPK and mTOR/S6K1 pathways in response to fasting. On the other hand, PASK deficiency prevents the development of obesity and non-alcoholic fatty liver in mice fed with a high-fat diet. This protection is explained by the re-establishment of several high-fat diet metabolic alterations produced in the expression of hepatic transcription factors and key enzymes that control the main metabolic pathways involved in maintaining metabolic homeostasis in fasting/feeding responses. This minireview covers the effects of PASK inactivation in the expression of certain transcription factors and target enzymes in several metabolic pathways under situations such as fasting and feeding with either a standard or a high-fat diet.
Highlights
Nutrient sensors are molecules that detect nutritional changes and coordinate adaptation responses to them in order to maintain cellular metabolic and energy homeostasis
They respond to changes in nutrients and to orexigenic peptides such as ghrelin [14, 15], or anorexigenic ones such as leptin [14, 16], and their activation/inhibition regulates hunger or satiety responses, and food intake
Schematic diagrams are provided of the activation degree of the AMPactivated protein kinase (AMPK) and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) pathways under fasting and refeeding conditions in control wild-type (WT) mice [Figure 1B (a)] and PASK-deficient mice [Figure 1B (b)] and in PASKsilenced cells [Figure 1B (d)] or control N2A cells [Figure 1B (c)] under low or high glucose concentrations
Summary
Nutrient sensors are molecules that detect nutritional changes and coordinate adaptation responses to them in order to maintain cellular metabolic and energy homeostasis. The first and most revealing data on the importance of PASK were forthcoming when PASK-deficient mice were subjected to a high-fat diet (HFD) [5]. This led to the study of how PASK deficiency protects against the development of obesity brought on by HFDs, being partly due to a high metabolic rate in skeletal muscle. This review contains the most recent evidence and advances made involving the mechanisms that allow PASK to play a decisive role in the control of multiple cellular functions related to cellular and organ response to fasting/feeding adaptation
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