Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria
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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/7/4047 |
| _version_ | 1797438864038559744 |
|---|---|
| author | Alexander Panov Vladimir I. Mayorov Sergey Dikalov |
| author_facet | Alexander Panov Vladimir I. Mayorov Sergey Dikalov |
| author_sort | Alexander Panov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T11:44:27Z |
| format | Article |
| id | doaj.art-58de5b33e8d347d8a6e26d8dab3aa9f4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:27Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58de5b33e8d347d8a6e26d8dab3aa9f42023-11-30T23:25:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237404710.3390/ijms23074047Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney MitochondriaAlexander Panov0Vladimir I. Mayorov1Sergey Dikalov2Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31201, USADepartment of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31201, USADivision of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USAWe 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.https://www.mdpi.com/1422-0067/23/7/4047metabolic syndromekidneyheartbrain mitochondriaβ-oxidationlong-chain fatty acids |
| spellingShingle | Alexander Panov Vladimir I. Mayorov Sergey Dikalov Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria International Journal of Molecular Sciences metabolic syndrome kidney heart brain mitochondria β-oxidation long-chain fatty acids |
| title | Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria |
| title_full | Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria |
| title_fullStr | Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria |
| title_full_unstemmed | Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria |
| title_short | Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria |
| title_sort | metabolic syndrome and β oxidation of long chain fatty acids in the brain heart and kidney mitochondria |
| topic | metabolic syndrome kidney heart brain mitochondria β-oxidation long-chain fatty acids |
| url | https://www.mdpi.com/1422-0067/23/7/4047 |
| work_keys_str_mv | AT alexanderpanov metabolicsyndromeandboxidationoflongchainfattyacidsinthebrainheartandkidneymitochondria AT vladimirimayorov metabolicsyndromeandboxidationoflongchainfattyacidsinthebrainheartandkidneymitochondria AT sergeydikalov metabolicsyndromeandboxidationoflongchainfattyacidsinthebrainheartandkidneymitochondria |