In Vivo Assessment of the Recovery of Myocardial Pyruvate Dehydrogenase Activity Following a Ketogenic Diet.

Details

• Alternative Title:
  Cardiovascular Research, 2026, v. 122, no. 6: In Vivo Assessment of the Recovery of Myocardial Pyruvate Dehydrogenase Activity Following a Ketogenic Diet.
• Journal Article:
  Cardiovascular Research
• Personal Author:
  Chen, Jun ; Erfani, Zohreh ; Elnwasany, Abdallah ; Nemri, Sarah Al ; Park, Joseph ; Huynh, Mai T. ; Zaidi, Maheen ; Harrison, Crystal E. ; Wen, Xiaodong ; Szweda, Luke I. ; Park, Jae Mo
• Description:
  A ketogenic diet (KD) can suppress cardiac carbohydrate utilization, which may adversely impact heart function. However, the reversibility of KD-induced metabolic changes is poorly understood. This study aims to characterize myocardial pyruvate dehydrogenase (PDH) flux during the transition from a prolonged KD to a normal chow diet (ND).
  
  Cardiac metabolism was longitudinally assessed in rats using hyperpolarized 1-13Cpyruvate at baseline, during a KD (2 and 5 weeks), and a subsequent ND (1, 2, 5, and 8 days) after the 5-week KD. Hyperpolarized 13C products were compared between the KD group and age-matched ND controls. In parallel, nuclear magnetic resonance isotopomer analysis of cardiac tissue with an injection of 3-13Cpyruvate and 1,2-13C2acetate was performed along with ex vivo enzymatic analysis of PDH activity. Myocardial 13Cbicarbonate production relative to total 13C products decreased from 8.56 ± 2.29% at baseline to 0.46 ± 0.27% after 5 weeks of KD. Reverting to ND gradually restored PDH flux (8.40 ± 1.47% by Day 8) to control levels (8.69 ± 2.10%). Ex vivo NMR analysis of glutamate C4 showed reduced pyruvate contribution to acetyl-CoA during KD (4.1 ± 2.5%), which recovered upon reverting to ND (22.7 ± 1.82% vs. control: 27.6 ± 9.5%). Although PDK4 expression normalized, PDH activity remained partially impaired in the reverted group (36.80 ± 6.07 mmol NADH/min/mg) compared to controls (90.97 ± 5.40; P = 0.00007).
  
  KD-induced suppression of myocardial PDH flux is reversible, but its recovery requires significant time, with prolonged metabolic inflexibility persisting after transitioning to an ND. These findings highlight the value of in vivo assessment of cardiac PDH activity, complemented by conventional enzymatic analyses, to identify persistent metabolic inflexibility following ketogenic interventions.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Diet, Ketogenic
  • Myocardium
  • Male
  • Rats, Sprague-Dawley
  • Time Factors
  • Pyruvate Dehydrogenase Complex
  • Energy Metabolism
  • Recovery of Function
  • Pyruvic Acid
  More +
• Keywords:
  • Original Article
  • Ketogenic diet
  • Hyperpolarization
  • Pyruvate dehydrogenase
  • Cardiac metabolism
  • Metabolic flexibility
• Source:
  Cardiovascular Research, 2026, v. 122, no. 6
• DOI:
  https://doi.org/10.1093/cvr/cvag053
• ISSN:
  0008-6363 ; 1755-3245
• Pubmed ID:
  41746829
• Pubmed Central ID:
  PMC13019313
• Document Type:
  Text
• Funding:
  P41 EB013598/EB/NIBIB NIH HHSUnited States/ ; S10 OD028490/OD/NIH HHSUnited States/ ; P30 DK127984/DK/NIDDK NIH HHSUnited States/ ; P41 EB015908/EB/NIBIB NIH HHSUnited States/ ; R01 NS107409/NS/NINDS NIH HHSUnited States/ ; S10 OD018468/OD/NIH HHSUnited States/ ; R01 HL170039/HL/NHLBI NIH HHSUnited States/ ; R01 NS107409/NS/NINDS NIH HHSUnited States/ ; R01 HL170039/HL/NHLBI NIH HHSUnited States/ ; P41 EB015908/EB/NIBIB NIH HHSUnited States/ ; S10 OD018468/CD/ODCDC CDC HHSUnited States/ ; S10 OD028490/CD/ODCDC CDC HHSUnited States/ ; P30 DK127984/DK/NIDDK NIH HHSUnited States/ ; W81XWH2210485/U.S. Army Medical Research Acquisition Activity/ ; HT94252510616/U.S. Army Medical Research Acquisition Activity/ ; MDA963281/Muscular Dystrophy Association/ ; Cancer Prevention and Research Institute of Texas/
• Genre:
  Journal Article
• Pages in Document:
  723-733 (21 pdf pages)
• Volume:
  122
• Issue:
  6
• Download URL:
  https://stacks.cdc.gov/view/cdc/260766/cdc_260766_DS1.pdf
• File Type:
  [PDF - 1.37 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0873191d72f3e53184323b3f0524800d1960bd2bd9d547ab249c88520a1df813936186327e3994668b5171efdf97fd9d647c16af824b155ffce36418370d372d