Abstract

Chinese giant salamander Andrias davidianus has strong tolerance to starvation. Fasting triggers a complex array of adaptive metabolic responses, a process in which the liver plays a central role. Here, a high-throughput proteomic analysis was carried out on liver samples obtained from adult A. davidianus after 3, 7, and 11 months of fasting. As a result, the expression levels of 364 proteins were significantly changed in the fasted liver. Functional analysis demonstrated that the expression levels of key proteins involved in fatty acid oxidation, tricarboxylic acid cycle, gluconeogenesis, ketogenesis, amino acid oxidation, urea cycle, and antioxidant systems were increased in the fasted liver, especially at 7 and 11 months after fasting. In contrast, the expression levels of vital proteins involved in pentose phosphate pathway and protein synthesis were decreased after fasting. We also found that fasting not only activated fatty acid oxidation and ketogenesis-related transcription factors PPARA and PPARGC1A, but also activated gluconeogenesis-related transcription factors FOXO1, HNF4A, and KLF15. This study confirms the central role of lipid and acetyl-CoA metabolism in A. davidianus liver in response to fasting at the protein level and provides insights into the molecular mechanisms underlying the metabolic response of A. davidianus liver to fasting.

Highlights

  • IntroductionThe organisms faced with reduced food intake have evolved efficient physiological and metabolic adaptations to extend their survival (Issartel et al, 2010)

  • Groundwater biotopes are characterized by poor and discontinuous food supplies

  • The results showed that alcohol dehydrogenase 1 (ADH1) was significantly down-regulated during fasting; YWHAE was significantly down-regulated after 7 months of fasting; FBP1 was significantly up-regulated after 7 months of fasting (Figure 2)

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Summary

Introduction

The organisms faced with reduced food intake have evolved efficient physiological and metabolic adaptations to extend their survival (Issartel et al, 2010). Several hypogean species are able to survive for long periods of food deprivation—nearly 1 year in invertebrates, and up to several years in cave fishes and salamanders (Hervant et al, 1999; Hervant et al, 2001). A study report proposed that the hypogean species had a lower metabolic rate, higher amounts of energy reserves (glycogen, triglycerides, and proteins) and reduction in utilization rates than epigean ones, enabling them to fuel energy metabolism for much longer without food (Hervant and Renault, 2002; Issartel et al, 2010). The liver is the central organ for metabolic activity in vertebrates and is an important storage depot for energy reserve (glycogen and lipids). Urodele amphibians have large amounts of glycogen in hepatocytes, and have larger amount of lipids than other vertebrates

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