Burmese pythons exhibit a transient adaptation to nutrient overload that prevents liver damage Journal Article uri icon

Overview

abstract

  • As an opportunistic predator, the Burmese python (Python molurus bivittatus) consumes large and infrequent meals, fasting for up to a year. Upon consuming a large meal, the Burmese python exhibits extreme metabolic responses. To define the pathways that regulate these postprandial metabolic responses, we performed a comprehensive profile of plasma metabolites throughout the digestive process. Following ingestion of a meal equivalent to 25% of its body mass, plasma lipoproteins and metabolites, such as chylomicra and bile acids, reach levels observed only in mammalian models of extreme dyslipidemia. Here, we provide evidence for an adaptive response to postprandial nutrient overload by the python liver, a critical site of metabolic homeostasis. The python liver undergoes a substantial increase in mass through proliferative processes, exhibits hepatic steatosis, hyperlipidemia-induced insulin resistance indicated by PEPCK activation and pAKT deactivation, and de novo fatty acid synthesis via FASN activation. This postprandial state is completely reversible. We posit that Burmese pythons evade the permanent hepatic damage associated with these metabolic states in mammals using evolved protective measures to inactivate these pathways. These include a transient activation of hepatic nuclear receptors induced by fatty acids and bile acids, including PPAR and FXR, respectively. The stress-induced p38 MAPK pathway is also transiently activated during the early stages of digestion. Taken together, these data identify a reversible metabolic response to hyperlipidemia by the python liver, only achieved in mammals by pharmacologic intervention. The factors involved in these processes may be relevant to or leveraged for remediating human hepatic pathology.

publication date

  • April 4, 2022

has restriction

  • gold

Date in CU Experts

  • March 29, 2022 9:13 AM

Full Author List

  • Magida JA; Tan Y; Wall CE; Harrison BC; Marr TG; Peter AK; Riquelme CA; Leinwand LA

author count

  • 8

Other Profiles

International Standard Serial Number (ISSN)

  • 0022-1295

Electronic International Standard Serial Number (EISSN)

  • 1540-7748

Additional Document Info

volume

  • 154

issue

  • 4