The Effects of Exogenous Lactate Administration on the IGF1/Akt/mTOR Pathway in Rat Skeletal Muscle.

Kiwon Lim,Hun-Young Park,Sunghwan Kyun,Jisu Kim,Choongsung Yoo

doi:10.3390/ijerph17217805

Abstract

We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague–Dawley rats were randomly divided into four groups (n = 8/group); their blood plasma levels of lactate, glucose, insulin, and insulin-like growth factor 1 (IGF1) were examined following sacrifice at 0, 30, 60, or 120 min after sodium lactate (2 g/kg) administration. We measured the mRNA expression levels of protein synthesis-related genes (IGF receptor, protein kinase B (Akt), mammalian target of rapamycin (mTOR)) or degradation-related genes (muscle RING-finger protein-1 (MuRF1), atrogin-1) and analyzed the protein expression and phosphorylation (activation) of Akt and mTOR. Post-administration, the plasma lactate concentration increased to 3.2 mmol/L after 60 min. Plasma glucose remained unchanged throughout, while insulin and IGF1 levels decreased after 30 min. The mRNA levels of IGF receptor and mTOR peaked after 60 min, and Akt expression was significantly upregulated from 30 to 120 min. However, MuRF1 and atrogin-1 expression levels were unaffected. Akt protein phosphorylation did not change significantly, whereas mTOR phosphorylation significantly increased after 30 min. Thus, lactate administration increased the mRNA and protein expression of protein-synthesis factors, suggesting that it can potentially promote skeletal muscle synthesis.

Highlights

40–50% of human body weight consists of skeletal muscle, which is characterized by plasticity
Muscle synthesis is induced by a number of factors in the body, among which the insulin-like growth factor 1 (IGF1)/protein kinase B (Akt)/mammalian target of rapamycin pathway has directly been shown to increase protein synthesis [3,4,5]
The primer sequences used to amplify the insulin-like growth factor 1 (IGF-1) receptor, protein kinase B (Akt), the mammalian target of rapamycin, muscle RING-finger protein-1 (MuRF1), and muscle-specific F-box protein mRNA in muscles were confirmed by Reverse transcription-polymerase chain reaction (RT-PCR)

Summary

Introduction

40–50% of human body weight consists of skeletal muscle, which is characterized by plasticity. 1 g/kg lactate administrated mice showed a supplemental effect on tibialis anterior weight and muscle fiber cross-sectional area [14] These findings revealed that lactate administration might increase the levels of factors driving protein synthesis. No studies of the changes in protein synthesis factors following lactate administration over time (e.g., 0, 30, 60, and 120 min) have been reported. The central hypothesis of this study was that exogenous lactate administration produces different responses in a time-dependent manner and can induce protein synthesis. To test this hypothesis, we administered lactate to rats, analyzed the mRNA and protein expression of protein synthesis- and protein degradation-related factors in skeletal muscles, and evaluated the blood factors in plasma

Animal Care

Animal Protocol

Blood Parameters

Western Blotting

Statistical Analysis

Results

Protein Expression of Akt and mTOR

Effect

Discussion

Conclusions