Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 6;23(7):4047.
doi: 10.3390/ijms23074047.

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Alexander Panov  1 , Vladimir I Mayorov  1 , Sergey Dikalov  2
Affiliations
Review

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria

Alexander Panov et al. Int J Mol Sci. .

Abstract

We present evidence that metabolic syndrome (MetS) represents the postreproductive stage of the human postembryonic ontogenesis. Accordingly, the genes governing this stage experience relatively weak evolutionary selection pressure, thus representing the metabolic phenotype of distant ancestors with β-oxidation of long-chain fatty acids (FAs) as the primary energy source. Mitochondria oxidize at high-rate FAs only when succinate, glutamate, or pyruvate are present. The heart and brain mitochondria work at a wide range of functional loads and possess an intrinsic inhibition of complex II to prevent oxidative stress at periods of low functional activity. Kidney mitochondria constantly work at a high rate and lack inhibition of complex II. We suggest that in people with MetS, oxidative stress is the central mechanism of the heart and brain pathologies. Oxidative stress is a secondary pathogenetic mechanism in the kidney, while the primary mechanisms are kidney hypoxia caused by persistent hyperglycemia and hypertension. Current evidence suggests that most of the nongenetic pathologies associated with MetS originate from the inconsistencies between the metabolic phenotype acquired after the transition to the postreproductive stage and excessive consumption of food rich in carbohydrates and a sedentary lifestyle.

Keywords: brain mitochondria; heart; human postembryonic ontogenesis; kidney; long-chain fatty acids; metabolic syndrome; oxidative stress; β-oxidation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Production of superoxide radicals by rat heart mitochondria oxidizing palmitoyl-carnitine. Designations: 1. supporting substrate only; 2. palmitoyl-carnitine only, and 3. palmitoyl-carnitine + supporting substrate. Substrates: (A)—pyruvate 2.5 mM + malate 2 mM, (B)—glutamate 5 mM + malate 2 mM, and (C)—succinate 5 mM. Experimental conditions are described in refs [57,60]. The numbers at the lines are the rates of ROS production in picomol of H2O2 per minute per mg of mitochondrial protein.
Figure 2
Figure 2
A schematic presentation of approximate differences between men and women in ROS production during ontogeny. The figure was adapted from ref [60].
Figure 3
Figure 3
Schematic presentation of the mitochondrial respirasome structure. The figure is based on the data presented in refs [66,67].
Figure 4
Figure 4
Kidney mitochondria do not possess the intrinsic inhibition of succinate dehydrogenase. Oxygen consumption was measured without ADP (State 4) or with ADP (State 3). (A) Mouse kidney mitochondria; (B) Rat brain mitochondria; (C) Rat heart mitochondria. The data are mean ± standard error. *** p < 0.001 vs. State 4 (n = 5). Redrawn from ref [75].
Figure 5
Figure 5
Effects of succinate, glutamate, and pyruvate on the resting oxidation of palmitoyl-carnitine (P-C) by the isolated kidney, brain, and heart mitochondria. Graphs show the oxygen consumption rates without ADP (State 4). (A) Mouse kidney mitochondria; (B) Rat brain mitochondria; (C) Rat heart mitochondria. The data are mean ± standard error. *** p < 0.001 Palm-Carnitine (P-C) vs. P-C + Succinate (n = 5); ** p < 0.01 P-C vs. P-C + Glutamate; * p < 0.05 and No-Difference Palm-Carnitine vs. P-C + Pyruvate. Redrawn from ref [75].
Figure 6
Figure 6
Effects of succinate, glutamate, and pyruvate on the rates of oxidative phosphorylation during oxidation of palmitoyl-carnitine (P-C) by the isolated kidney, brain, and heart mitochondria. Graphs show the oxygen consumption rates with ADP (State 3). (A) Mouse kidney mitochondria; (B) Rat brain mitochondria; (C) Rat heart mitochondria. The data are mean ± standard error. *** p < 0.01 Palm-Carnitine (P-C) vs. P-C + Succinate, P-C + Glutamate, and P-C + Pyruvate; * p < 0.05 Palm-Carnitine vs. P-C + Pyruvate (A) (n = 5). Redrawn from ref [75].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bertermann H., Gronow G., Schirmer A., Weiss C. Contribution of long chain fatty acids to the energy supply of the rat kidney cortex. Pflug. Arch. 1975;356:9–17. doi: 10.1007/BF00583517. - DOI - PubMed
    1. Wirthensohn G., Guder W.G. Triacylglycerol metabolism in isolated rat kidney cortex tubules. Biochem. J. 1980;186:317–324. doi: 10.1042/bj1860317. - DOI - PMC - PubMed
    1. Schonfeld P., Reiser G. Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain. J. Cereb. Blood Flow Metab. 2013;33:1493–1499. doi: 10.1038/jcbfm.2013.128. - DOI - PMC - PubMed
    1. Schonfeld P., Reiser G. Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration. Neurochem. Int. 2017;109:68–77. doi: 10.1016/j.neuint.2017.03.018. - DOI - PubMed
    1. Julius U., Leonhardt W., Schulze J., Schollberg K., Hanefeld M., Haller H. Hyperinsulinemia in patients with low fractional catabolic rate of triglycerides. Acta Diabetol. Lat. 1981;18:217–223. doi: 10.1007/BF02047893. - DOI - PubMed