Fetal Cardiac Lipid Sensing Triggers an Early and Sex-Related Metabolic Energy Switch in Intrauterine Growth Restriction

2021 ◽  
Author(s):  
Loïze Maréchal ◽  
Benoit Sicotte ◽  
Véronique Caron ◽  
Michèle Brochu ◽  
André Tremblay
Keyword(s):  
Fatty Acids ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Metabolic Energy ◽  
Long Chain Fatty Acids ◽  
Intrauterine Growth ◽  
Lipidomic Analysis ◽  
Vascular Insufficiency ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract CONTEXT Intrauterine growth restriction (IUGR) is an immediate outcome of an adverse womb environment, exposing newborns to developing cardiometabolic disorders later in life. This study investigates the cardiac metabolic consequences and underlying mechanism of energy expenditure in developing fetuses under conditions of IUGR. METHODS Using an animal model of IUGR characterized by uteroplacental vascular insufficiency, mitochondrial function, gene profiling, lipidomic analysis, and transcriptional assay were determined in fetal cardiac tissue and cardiomyocytes. RESULTS IUGR fetuses exhibited an upregulation of key genes associated with fatty acid breakdown and β-oxidation (Acadvl, Acadl, Acaa2), and mitochondrial carnitine shuttle (Cpt1a, Cpt2), instigating a metabolic gene reprogramming in the heart. Induction of Ech1, Acox1, Acox3, Acsl1, and Pex11a indicated a coordinated interplay with peroxisomal β-oxidation and biogenesis mainly observed in females, suggesting sexual dimorphism in peroxisomal activation. Concurring with the sex-related changes, mitochondrial respiration rates were stronger in IUGR female fetal cardiomyocytes, accounting for enhanced ATP production. Mitochondrial biogenesis was induced in fetal hearts with elevated expression of Ppargc1a transcript specifically in IUGR females. Lipidomic analysis identified accumulation of arachidonic, eicosapentaenoic, and docosapentaenoic polyunsaturated long-chain fatty acids in IUGR fetal hearts, which lead to nuclear receptor PPARα transcriptional activation in cardiomyocytes. Also, enrichment of H3K27ac chromatin marks to PPARα responsive metabolic genes in IUGR fetal hearts outlines an epigenetic control in the early metabolic energy switch. CONCLUSION These data are consistent with a premature and sex-related remodeling of cardiac metabolism in response to an unfavorable intrauterine environment, with specific long-chain fatty acids that may serve as predictive effectors leading to IUGR.

scholarly journals Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Liver Injury ◽  
Olive Oil ◽  
Coconut Oil ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

Long chain fatty acids can form aggregates and affect the membrane integrity

2021 ◽  
Vol 204 ◽  
pp. 111795
Author(s):  
Gulen Melike Demirbolat ◽  
Goknil Pelin Coskun ◽  
Omer Erdogan ◽  
Ozge Cevik
Keyword(s):  
Fatty Acids ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals Ca2+/Calmodulin-independent Activation of Calcineurin fromDictyosteliumby Unsaturated Long Chain Fatty Acids

1999 ◽  
Vol 274 (53) ◽  
pp. 37821-37826 ◽  
Author(s):  
Ursula Kessen ◽  
Ralph Schaloske ◽  
Annette Aichem ◽  
Rupert Mutzel
Keyword(s):  
Fatty Acids ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids
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