Abstract

Alterations in markers of mitochondrial content with ketogenic diets (KD) have been reported in tissues of rodents, but morphological quantification of mitochondrial mass using transmission electron microscopy (TEM), the gold standard for mitochondrial quantification, is needed to further validate these findings and look at specific regions of interest within a tissue. In this study, red gastrocnemius muscle, the prefrontal cortex, the hippocampus, and the liver left lobe were used to investigate the impact of a 1-month KD on mitochondrial content in healthy middle-aged mice. The results showed that in red gastrocnemius muscle, the fractional area of both subsarcolemmal (SSM) and intermyofibrillar (IMM) mitochondria was increased, and this was driven by an increase in the number of mitochondria. Mitochondrial fractional area or number was not altered in the liver, prefrontal cortex, or hippocampus following 1 month of a KD. These results demonstrate tissue-specific changes in mitochondrial mass with a short-term KD and highlight the need to study different muscle groups or tissue regions with TEM to thoroughly determine the effects of a KD on mitochondrial mass.

Highlights

  • An increase in mitochondrial mass has been proposed as one underlying mechanism for the therapeutic and health-promoting effects of ketogenic diets (KD) [1,2]

  • It is not known whether mitochondrial mass in specific muscle groups or regions within a tissue may be altered with a KD

  • To investigate mitochondrial mass in a specific hindlimb muscle, Transmission electron microscopy (TEM) analysis w be driven by an increase in the number of mitochondria in both regions

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Summary

Introduction

An increase in mitochondrial mass has been proposed as one underlying mechanism for the therapeutic and health-promoting effects of ketogenic diets (KD) [1,2]. We have previously used a panel of common mitochondrial markers to thoroughly investigate the impact of a KD started in early middle-aged mice on mitochondrial mass in whole-tissue homogenates of hindlimb skeletal muscle, brain, and liver, and after 1 month of intervention, no concerted changes in markers of mitochondrial mass were observed [10]. It is not known whether mitochondrial mass in specific muscle groups or regions within a tissue may be altered with a KD. TEM is needed to further unravel possible KD-induced changes in mitochondrial mass, and the use of TEM allows the selection of specific regions of interest within a tissue

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