Differential Proteomic Analysis of Chinese Giant Salamander Liver in Response to Fasting

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.

Caloric restriction remodels the hepatic chromatin landscape and bile acid metabolism by modulating the gut microbiota

“…Binding sites of key transcription factors essential for fatty acid oxidation and bile acid biosynthesis were also enriched, including PPARα and HNF4α [ 21 – 24 ]. To this end, we used WB and qPCR to validate the expressions of the two signal-responsive TFs.…”

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

“…Hepatic KLF15 expression was regulated by glucagon and insulin, which was induced during fasting or inhibited during feeding (Yamamoto et al, 2004;Teshigawara et al, 2005;Li et al, 2020). High-throughput proteomic analysis of liver samples obtained from adult giant salamanders during fasting for 3, 7, and 11 months revealed fasting activated not only the fatty acid oxidation and ketogenesis-related transcription factors PPAR-α and PPARγ-C1α, but also the gluconeogenesis-related transcription factors forkhead box O-class 1 (FoxO1), hepatocyte nuclear factor 4 alpha (HNF4α), and KLF15 (Geng et al, 2020). In the process, glucose was supplied to the blood using free amino acids produced by proteolysis in muscle and other tissues through glycogenolysis and gluconeogenesis in the liver (Oh et al, 2013;Melkonian et al, 2022).…”