Table III.
Summary table indicating the mitochondrial manifestations and the molecular targets that are affected during the ketogenic diet.
| Ketogenic diet
| |||
|---|---|---|---|
| Phenotype | Tissue (host) | Molecular target | (Refs). |
| Biogenesis/function | Cardiac muscle Sprague-Dawley rats Interscapular brown adipose tissue (IBAT) C57BL/6 mice | ↥ Mitochondrial number ↥ Electron transport chain proteins UCP1 protein ↥ AMPK, PPAR-γ, PGC-1α proteins |
(137) |
| Biogenesis | Liver Wistar rats | ↥ mRNA PPARGC1α and TFAM | (139) |
| Biogenesis | Skeletal muscle, liver, brain from Fisher Rats and mice | - PGC-1α protein levels | (124,126) |
| Biogenesis/dynamics | Skeletal muscle C57BL/6 mice | ↥ PGC-1α protein ↥ Mitochondrial fission/fusion related genes |
(141) |
| Function | Liver male C57BL/6 mice | ↥ Mitochondrial fatty acid oxidation ↥ de novo lipogenesis |
(124) |
| Function | Skeletal muscle C57BL/6 mice | ↧ Mitochondrial activity (TFAM, SIRT1, SIRT3, PGC-1a) in younger animals ↥ Mitochondrial mass (level of OXPHOS) and function (citrate synthase activity) in elder animals |
(125) |
| Function | Liver and skeletal muscle Fisher rats | ↥ Citrate synthase activity ↥ Mitochondrial volume |
(126) |
| Function | Skeletal muscle Sprague-Dawley rats | ↥ Efficiency of coupling of complex II substrates (respiratory control ratio of isolated mitochondria) | (123) |
| Function | Liver C57Bl/6 mice | ↧ Hepatic cytochrome c and complex IV levels | (122) |
| Function | Skeletal muscle Fisher rats | ↧ citrate synthase activity | (128) |
| Function/dynamics | Cardiac muscle type-2 diabetic db/db mice | ↧ Mitochondrial fission (mitochondrial number, size) ↥ PI3K, p-Akt, Akt, mitochondrial respiratory control ratio, ATP content |
(134) |
| Function | Myocardium tissue of male Sprague-Dawley rats | ↧ HDAC2 leading to the transcriptional activation of SIRT7 | (129) |
| Function | Cybrid cell lines from a patient with Kearns-Sayre syndrome (KSS) | ↥ Mitochondrial volume | (130) |
| Function | Brain and muscle tissue BTBR mice | ↥ Mitochondrial morphological deformations | (131) |
| Function | Skeletal muscle from healthy human subjects | ↥ Mitochondrial respiratory control ratio (mitochondrial O2 consumption and membrane potential index) ↥ ATP production ↥ ATP/H2O2 ratio |
(132) |
| Function | Skeletal muscle Fisher rats | ↧ H2O2 emission ↥ Mitochondrial respiration ↥↥ Cell viability |
(133) |
| Function | Skeletal muscle Twinkledupl transgenic mice | ↧ Amount of cytochrome c oxidase negative muscle fibers | (136) |
| Function | Liver male C57BL/6 mice | ↥ mRNA expression PPARGC1α | (140) |
| Dynamics | Liver C57Bl/6 and BTBR mice | ↧ Mitochondrial amount (decrease mtDNA) ↥ BNIP3 mRNA and protein |
(143) |
| Dynamics | Skeletal muscle C57BL/6 mice | ↥ Markers mitochondrial content (citrate synthase, Complex I, and Complex IV activity) | (127) |
| Dynamics | Cardiomyocytes of rabbits with heart failure | ↧ Mitofusin 2 (MFN2) and dynamin-related protein 1 (DRP1) | (144) |
| Dynamics | SH-SY-5Y cells | ↧ Dynamin-related protein1 (DRP1) | (145) |
| Mitophagy | Hepatocytes of male and female Wistar rats | ↧ Markers of de novo lipogenesis (FAS, ACC) | (139) |
| Mitophagy | Liver C57BL/6 and BTBR mice | ↥ BNIP3 protein | (143) |
Upward arrows indicate an increase, and downward arrows indicate a decrease. UCP1, uncoupling protein 1; AMPK, AMP-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator 1α; TFAM, mitochondrial transcription factor A; mtDNA, mitochondrial DNA; SIRT1, sirtuin 1; DRP1, dynamin-related protein 1.