# Effects of AMPK/PGC-1α on gluconeogenesis in skeletal muscle of animals under overwintering starvation and its molecular mechanism: review

## TL;DR

This paper reviews how animals survive winter starvation by activating specific muscle pathways to maintain energy balance.

## Contribution

It provides new insights into the AMPK/PGC-1α signaling pathway's role in skeletal muscle gluconeogenesis during overwintering starvation.

## Key findings

- AMPK/PGC-1α signaling increases FOXO1 and PDK4 activity, upregulating gluconeogenesis genes PEPCK and G6Pase.
- The pathway enhances fat oxidation and glycerol production to support gluconeogenesis in skeletal muscle.
- These mechanisms help animals maintain energy homeostasis during low temperature and starvation.

## Abstract

During the wintering period characterized by feed scarcity, animals activate the sympathetic nervous system (SNS)-β-adrenergic receptor (βAR)-AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling pathway in their bodies. This activation increases the transcriptional activity of forkhead box O1 (FOXO1) transcription factor and pyruvate dehydrogenase kinase 4 (PDK4), leading to the upregulation of gluconeogenesis-limiting genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Additionally, it enhances the functions of carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 1 (UCP1), cluster of differentiation 36 (CD36), and fatty acid transport protein (FATP). This promotes promote intermuscular fat oxidation and the production of gluconeogenesis precursor glycerol, thereby enhancing animal skeletal muscle gluconeogenesis to maintain animal energy homeostasis and life activities under low temperature and starvation conditions. This article describes the effects of overwintering starvation stress on the AMPK/PGC-1α signaling pathway and its molecular mechanism in animal skeletal muscle gluconeogenesis. The aim to provide a theoretical basis for optimizing sustainable breeding strategies and improving animal production performance in alpine regions.