scholarly journals Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eric S. Goetzman ◽  
Sivakama S. Bharathi ◽  
Yuxun Zhang ◽  
Xue-Jun Zhao ◽  
Steven F. Dobrowolski ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Knockout Mice ◽  
Coconut Oil ◽  
Degradation Pathway ◽  
Acid Oxidation ◽  
Synthetase Activity ◽  
Alcoholic Fatty Liver ◽  
Medium Chain ◽  
Macrovesicular Steatosis

Abstract Medium-chain triglycerides (MCT), containing C8–C12 fatty acids, are used to treat several pediatric disorders and are widely consumed as a nutritional supplement. Here, we investigated the role of the sirtuin deacylase Sirt5 in MCT metabolism by feeding Sirt5 knockout mice (Sirt5KO) high-fat diets containing either C8/C10 fatty acids or coconut oil, which is rich in C12, for five weeks. Coconut oil, but not C8/C10 feeding, induced periportal macrovesicular steatosis in Sirt5KO mice. 14C–C12 degradation was significantly reduced in Sirt5KO liver. This decrease was localized to the mitochondrial β-oxidation pathway, as Sirt5KO mice exhibited no change in peroxisomal C12 β-oxidation. Endoplasmic reticulum ω-oxidation, a minor fatty acid degradation pathway known to be stimulated by C12 accumulation, was increased in Sirt5KO liver. Mice lacking another mitochondrial C12 oxidation enzyme, long-chain acyl-CoA dehydrogenase (LCAD), also developed periportal macrovesicular steatosis when fed coconut oil, confirming that defective mitochondrial C12 oxidation is sufficient to induce the steatosis phenotype. Sirt5KO liver exhibited normal LCAD activity but reduced mitochondrial acyl-CoA synthetase activity with C12. These studies reveal a role for Sirt5 in regulating the hepatic response to MCT and may shed light into the pathogenesis of periportal steatosis, a hallmark of human pediatric non-alcoholic fatty liver disease.

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.

scholarly journals Recent Advances in the Pathophysiology of Fatty Acid Oxidation Defects: Secondary Alterations of Bioenergetics and Mitochondrial Calcium Homeostasis Caused by the Accumulating Fatty Acids

2020 ◽  
Vol 11 ◽  
Author(s):  
Alexandre Umpierrez Amaral ◽  
Moacir Wajner
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Calcium Homeostasis ◽  
Acid Oxidation ◽  
Cultured Fibroblasts ◽  
Medium Chain ◽  
Chain Acyl ◽  
Energy Deprivation ◽  
Long Chain

Deficiencies of medium-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein, isolated long-chain 3-hydroxyacyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase activities are considered the most frequent fatty acid oxidation defects (FAOD). They are biochemically characterized by the accumulation of medium-chain, long-chain hydroxyl, and long-chain fatty acids and derivatives, respectively, in tissues and biological fluids of the affected patients. Clinical manifestations commonly include hypoglycemia, cardiomyopathy, and recurrent rhabdomyolysis. Although the pathogenesis of these diseases is still poorly understood, energy deprivation secondary to blockage of fatty acid degradation seems to play an important role. However, recent evidence indicates that the predominant fatty acids accumulating in these disorders disrupt mitochondrial functions and are involved in their pathophysiology, possibly explaining the lactic acidosis, mitochondrial morphological alterations, and altered mitochondrial biochemical parameters found in tissues and cultured fibroblasts from some affected patients and also in animal models of these diseases. In this review, we will update the present knowledge on disturbances of mitochondrial bioenergetics, calcium homeostasis, uncoupling of oxidative phosphorylation, and mitochondrial permeability transition induction provoked by the major fatty acids accumulating in prevalent FAOD. It is emphasized that further in vivo studies carried out in tissues from affected patients and from animal genetic models of these disorders are necessary to confirm the present evidence mostly achieved from in vitro experiments.

scholarly journals Analysis of Fatty Acids in Virgin Coconut Oil Frying at Various Temperatures

2021 ◽  
Vol 10 (1) ◽  
pp. 104
Author(s):  
Dewa Ayu Ika Pramitha ◽  
I Wayan Karta
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Acid Content ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Medium Chain Triglyceride ◽  
Coconut Oil ◽  
Virgin Coconut Oil ◽  
Medium Chain ◽  
Cooking Oil

Fatty acid content from virgin coconut oil (VCO) is a medium-chain triglyceride (MCT) group. MCT is stable at very low and high temperatures, and the color does not turn black due to the addition of heat so that it can be developed into beneficial cooking oil for health. Therefore, a study was conducted on the content of fatty acids in VCO after being heated at temperatures of 150, 200, and 250°C for 60 minutes. Analysis of fatty acid content in control VCO(T0), VCO with heating temperatures of 150oC(T1), 200oC(T2), and 250oC(T3) was performed with GCMS QP-2010 Ultra.The results showed that there were differences in levels and types of fatty acids in VCO by treating T0, T1, T2, and T3. At these three temperatures still produce medium-chain saturated fatty acids and trans fatty acids are not produced, so that VCO can be utilized as cooking oil that has better stability and benefits for health.

Mitochondrial and peroxisomal fatty acid oxidation in elasmobranchs

1990 ◽  
Vol 258 (3) ◽  
pp. R756-R762 ◽  
Author(s):  
C. D. Moyes ◽  
L. T. Buck ◽  
P. W. Hochachka
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Salmo Gairdneri ◽  
Acid Oxidation ◽  
Beta Oxidation ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Palmitoyl Carnitine ◽  
Red Muscle ◽  
Chain Fatty Acids

In heart and red muscle of dogfish (Squalus acanthias), the maximal activities of the fatty acid catabolizing enzyme carnitine palmitoyltransferase (CPT) are less than 5% the rate in the same tissues of teleosts (carp, Cyprinus carpio; trout, Salmo gairdneri). CPT activities in these tissues of hagfish (Eptatretus stouti) are approximately 10% the rate in teleosts. However, the maximal activities of the beta-oxidation enzyme beta-hydroxyacyl-CoA dehydrogenase (HOAD) in dogfish red muscle and heart are similar to these tissues in the other species. This paradox prompted a more detailed study on the capacity of mitochondria from dogfish cardiac and red skeletal muscles to utilize fatty acids, possibly by a CPT-independent pathway. Free fatty acids were not oxidized by mitochondria from red muscle (hexanoate, octanoate, decanoate, and palmitate) or from heart (octanoate, palmitate). Neither hyposmotic incubation nor addition of 5 mM ATP could stimulate oxidation of octanoate or palmitate in either preparation, suggesting that these tissues have little capacity to oxidize fatty acids by a carnitine-independent pathway. Palmitoyl carnitine oxidation was detectable at very low rates in these mitochondria only with hyposmotic incubation. Octanoyl carnitine was oxidized at greater rates than palmitoyl carnitine, 10% the rate of pyruvate in both tissues, suggesting that medium-chain fatty acids could be physiologically relevant fuels in elasmobranchs if available to heart and red muscle. One potential source of medium-chain fatty acids is hepatic peroxisomal beta-oxidation, which occurs in dogfish liver at maximal activities similar to carp and trout liver. However, based on relative rates of oxidation, it is likely that dogfish heart and red muscle metabolism are fueled primarily by carbohydrate and ketone bodies.

scholarly journals Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10556
Author(s):  
Khaled I. Alatibi ◽  
Stefan Tholen ◽  
Zeinab Wehbe ◽  
Judith Hagenbuchner ◽  
Daniela Karall ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Oxidation Disorders ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Long Chain

Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor. However, mc-FAs induced a remodeling of complex lipids. Especially C7 appeared to act protectively by restoring sphingolipid biosynthesis flux and improving the observed dysregulation of protein homeostasis in LCHADD under control conditions.

Lipid metabolism in Achlya: studies of lipid turnover during development

1976 ◽  
Vol 22 (12) ◽  
pp. 1710-1715 ◽  
Author(s):  
Simon W. T. Law ◽  
David N. Burton
Keyword(s):  
Fatty Acids ◽  
Life Cycle ◽  
Fatty Acid ◽  
Total Lipid ◽  
Fatty Acid Synthetase ◽  
Principal Component ◽  
Dry Weight ◽  
Acid Oxidation ◽  
Synthetase Activity ◽  
Lipid Turnover

The life cycle of Achlya involves germination of spores to form coenocytic somatic hyphae, followed by differentiation of hyphal tips into sporangia. From germination to release of new spores occupies 27–30 h. Total lipid made up 10% of dry weight in ungerminated spores. After germination, total lipid fell to 6% of dry weight in 15 h, then rose to7.7% at the time of sporangium formation. Half of the initial loss of lipid took place within 2 h of germination. The ability of Achlya to incorporate [1-14C]acetate into lipid was maximal at the time of sporangium formation, and glycerides were the principal component of total lipid to become 14C-labelled at all stages of the life cycle. Fatty acid synthetase activity measured in cell-free extracts was low in spores and in actively elongating mycelium, but increased during differentiation to a level 15-fold greater than that in spores. Fatty acid oxidation, as estimated by the release of 14CO2 from 1-14C-labelled fatty acids, was also maximal at the time of sporangium formation.

scholarly journals Influence of virgin coconut oil-enriched diet on the transcriptional regulation of fatty acid synthesis and oxidation in rats – a comparative study

2014 ◽  
Vol 111 (10) ◽  
pp. 1782-1790 ◽  
Author(s):  
Sakunthala Arunima ◽  
Thankappan Rajamohan
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Coconut Oil ◽  
Acid Oxidation ◽  
Virgin Coconut Oil

The present study was carried out to evaluate the effects of virgin coconut oil (VCO) compared with copra oil, olive oil and sunflower-seed oil on the synthesis and oxidation of fatty acids and the molecular regulation of fatty acid metabolism in normal rats. Male Sprague–Dawley rats were fed the test oils at 8 % for 45 d along with a synthetic diet. Dietary supplementation of VCO decreased tissue lipid levels and reduced the activity of the enzymes involved in lipogenesis, namely acyl CoA carboxylase and fatty acid synthase (FAS) (P< 0·05). Moreover, VCO significantly (P< 0·05) reduced thede novosynthesis of fatty acids by down-regulating the mRNA expression of FAS and its transcription factor, sterol regulatory element-binding protein-1c, compared with the other oils. VCO significantly (P< 0·05) increased the mitochondrial and peroxisomal β-oxidation of fatty acids, which was evident from the increased activities of carnitine palmitoyl transferase I, acyl CoA oxidase and the enzymes involved in mitochondrial β-oxidation; this was accomplished by up-regulating the mRNA expression of PPARα and its target genes involved in fatty acid oxidation. In conclusion, the present results confirmed that supplementation of VCO has beneficial effects on lipid parameters by reducing lipogenesis and enhancing the rate of fatty acid catabolism; this effect was mediated at least in part via PPARα-dependent pathways. Thus, dietary VCO reduces the risk for CHD by beneficially modulating the synthesis and degradation of fatty acids.

Nutritional Values and Health Protective Properties Of Coconut Oil

2020 ◽  
Vol 3 (2) ◽  
pp. 1-12
Author(s):  
Jansen Silalahi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Coconut Oil ◽  
Medium Chain Triglycerides ◽  
Nutritional Values ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Long Chain Triglycerides ◽  
Long Chain ◽  
Chain Fatty Acids

Chemically, fat or oil is a mixture of triacylglycerol molecules, in which glycerol esterified with three fatty acids. Fatty acid is a monocarboxilic acid containing even number of carbon atom started from 4 to 22. Based on the length of fatty acid in triacylglycerol, fats and oils can be classified into two groups; medium chain triglycerides and long chain triglycerides. Coconut oil belongs to medium chain triglycerides oil because it’s fatty acids consist mostly of medium chain fatty acids (C4:0 to C12:0) and dominated by lauric acid (C12:0), hence usually called as lauric oil. In the year of 1950s, coconut oil was claimed that saturated fats, including coconut oil, could increase blood total cholesterol and hence is atherogenic, while unsaturated fats decrease total cholesterol. However, in 1990s, coconut oil was found to be different from the other saturated oils. Coconut oil composed of medium chain fatty acids with high amount of lauric acid. Coconut oil is metabolized differently from long chain triglycerides saturated oil, and therefore coconut oil has numerous beneficial nutritional values and health promotion. Consumption of food rich in medium chain fatty acids reduces the level of body fat and the decrease the risk of heart disease, diabetes, increase mother’s milk quality and active as potential antibacterial agent.  

Sign in / Sign up

Export Citation Format

Share Document