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Fatty Acid Uptake by the Heart During Fasting

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Handbook of Famine, Starvation, and Nutrient Deprivation

Abstract

The heart consumes the highest energy substrates per weight in the entire body. The heart preferentially uses fatty acids (FAs) as energy-providing substrates; 60–90% of cardiac adenosine triphosphate (ATP) is derived from FA oxidation (FAO), with the remaining derived from glucose, lactate, ketone bodies, and amino acids. During fasting, FAO is increased, whereas glucose utilization is reduced. Sources of FAs in circulation are free FA (FFA) bound to albumin and two forms of triglyceride-rich lipoproteins (TGRLP), chylomicrons (CM), and very-low-density lipoproteins (VLDL). Following lipolysis of TG (triglyceride) of TGRLP on the cell surface of endothelial cells, FAs traverse the muscle-type continuous capillary layer via protein-mediated and/or nonprotein-mediated pathways. In turn, FAs bound to albumin in the interstitial space are taken up by the heart via the flip-flop mechanism, which is likely facilitated by several plasma-membrane proteins, including FAT (FA translocase)/CD36. Most FAs are utilized in the heart to generate ATP and the remaining FAs are used as TG storage, membrane phospholipid components, and lipid mediators. During fasting, FA uptake and oxidation are enhanced via transcriptional activation by peroxisome proliferator-activated receptor γ (PPARγ) in capillary endothelial cells and by PPARα and PPARγ coactivator-1α (PGC-1α) in cardiomyocytes. Inherited disorders that affect FAO compromise the function of the heart in catabolic states, such as fasting, which causes sudden infant death syndrome. This section describes the mechanisms that regulate FA uptake by the heart in the fed or fasted state as well as the effects of fasting on cardiac function.

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Abbreviations

ATP:

Adenosine triphosphate

CM:

Chylomicrons

ECs:

Endothelial cells

ETC:

Electron transport chain

FABP:

Fatty acid binding protein

FAD:

Flavin adenine dinucleotide

FAO:

Fatty acid oxidation

FAT:

Fatty acid translocase

FATP:

Fatty acid transport protein

FFA:

Free fatty acid

GPIHBP1:

Glycosylphosphatidylinositol-anchored protein 1

LPL:

Lipolysis, lipoprotein lipase

Meox2:

Mesodermal homeobox-2

NAD:

Nicotinamide adenine dinucleotide

PDH:

Pyruvate dehydrogenase

PDK4:

Pyruvate dehydrogenase kinase 4

PGC-1α:

PPARγ coactivator-1α

PPAR:

Peroxisome proliferator-activated receptor

PPRE:

PPAR response elements

REE:

Resting energy expenditure

RXR:

Retinoid X receptor

TCA cycle:

Tricarboxylic acid cycle

Tcf15:

Transcription factors 15

TG:

Triglyceride

TGRLP:

TG-rich lipoproteins

VEGF-B:

Vascular endothelial growth factor-B

VLDL:

Very-low-density lipoproteins

VLDLR:

VLDL receptor

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Author information

Authors and Affiliations

  1. Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Tatsuya Iso & Masahiko Kurabayashi

  2. Education and Research Support Centre, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Tatsuya Iso

  3. Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Masahiko Kurabayashi

Authors
  1. Tatsuya Iso
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  2. Masahiko Kurabayashi
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Correspondence to Tatsuya Iso .

Editor information

Editors and Affiliations

  1. Diabetes & Nutritional Sci Div Sch, King's College London, London, United Kingdom

    Victor Preedy

  2. Clinical Biochemistry, University of Westminster, Westminster, United Kingdom

    Vinood B. Patel

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Iso, T., Kurabayashi, M. (2017). Fatty Acid Uptake by the Heart During Fasting. In: Preedy, V., Patel, V. (eds) Handbook of Famine, Starvation, and Nutrient Deprivation. Springer, Cham. https://doi.org/10.1007/978-3-319-40007-5_13-1

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  • DOI: https://doi.org/10.1007/978-3-319-40007-5_13-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40007-5

  • Online ISBN: 978-3-319-40007-5

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