Effects of D-beta-hydroxybutyrate and long- and medium-chain triglycerides on leucine metabolism in humans

1992 ◽  
Vol 262 (3) ◽  
pp. E268-E274 ◽  
Author(s):  
B. Beaufrere ◽  
D. Chassard ◽  
C. Broussolle ◽  
J. P. Riou ◽  
M. Beylot

Ketone bodies and/or fatty acids might play a protein-sparing role during prolonged fasting or parenteral nutrition. To assess this problem, we studied whole body leucine metabolism, using L-[1-13C]leucine in normal postabsorptive volunteers who received either long-chain triglycerides (LCT, 0.15 g.kg-1.h-1, 6 subjects), a 50-50 mixture of medium-chain triglycerides (MCT) and LCT (0.15 g.kg-1.h-1, 6 subjects), D-beta-hydroxybutyrate (540 mumol.kg-1.h-1, 6 subjects), or saline (4 subjects). Leucine concentration decreased only with MCT-LCT. Leucine flux decreased by 10-20% from basal in all groups. Leucine oxidation, which was corrected for the contribution to 13CO2 of the 13C natural abundance of the infused substrates, decreased during LCT infusion (0.31 +/- 0.02 to 0.24 +/- 0.01 mumol.kg-1.min-1, P less than 0.01), but was unaffected by MCT-LCT (despite plasma free fatty acid levels similar to those obtained with LCT), D-beta-hydroxybutyrate, or saline infusion. Therefore, 1) the effect of fatty acids on amino acid oxidation is not mediated by ketone bodies, 2) it depends on the fatty acid chain length, 3) long-chain fatty acids but not medium-chain fatty acids could play a protein-sparing role during parenteral nutrition.

Author(s):  
Jansen Silalahi

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.  


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  

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.


1991 ◽  
Vol 10 (3) ◽  
pp. 325-340 ◽  
Author(s):  
D. R. Webb ◽  
R. A. Sanders

Caprenin (CAP) is a triglyceride that primarily contains caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids. This study was undertaken to determine whether or not CAP is qualitatively digested, absorbed, and rearranged like other dietary fats and oils that contain these medium-chain and very long-chain fatty acids. In vitro results showed that neat CAP, coconut oil (CO) and peanut oil (PO) were hydrolyzed by porcine pancreatic lipase. All of the neat triglycerides also were digested in vivo by both male and female rats. This was shown by the recovery of significantly more extractable lymphatic fat than with fat-free control animals and by the recovery of orally administered triglyceride-derived fatty acids in lymph triglycerides. However, substantially more PO (74%) and CO (51%) were recovered in lymph relative to CAP (10%). These quantitative differences are consistent with the fatty acid composition of each triglyceride and primary routes of fatty acid uptake. The 24-h lymphatic recovery of CAP-derived C8:0, C10:0, and C22:0 averaged 3.9%, 17.8%, and 11.2%, respectively, for male and female rats. The C8:0 and C10:0 results approximated those obtained with CO (2.0% and 16.3%, respectively). In contrast, the 24-h absorbability of C22:0 in CAP was significantly less than that seen in PO (55.4%). Finally, there was no evidence of significant rearrangement of the positions of fatty acids on glycerol during digestion and absorption. Those fatty acids recovered in lymphatic fat tended to occupy the same glyceride positions that they did in the neat administered oils. However, the lymph fats recovered from all animals dosed with fat emulsions were enriched with endogenous lymph fatty acids. It is concluded that CAP is qualitatively digested, absorbed, and processed like any dietary fat or oil that contains medium-chain and very long-chain fatty acids.


PEDIATRICS ◽  
1989 ◽  
Vol 83 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Margit Hamosh ◽  
Joel Bitman ◽  
Teresa H. Liao ◽  
N. R. Mehta ◽  
R. J. Buczek ◽  
...  

The extent of gastric lipolysis, fat absorption, and infant weight gain was studied in 12 preterm infants (gestational age 28.75 ± 0.50 weeks, postnatal age 6.08 ± 0.81 weeks) fed medium-chain triglyceride or long-chain triglyceride formula for 1 week in a crossover design. The former formula contained 42% of 8:0 and 10:0 and 19% of 12:0, 14:0, and 16:0; the latter formula contained only 7% of 8:0 and 10:0 and 46% of 12:0, 14:0, and 16:0. Gastric aspirates were obtained on the second and third day of formula feeding for quantitation of lipase activity and of the extent of gastric lipolysis. Fat balance studies were conducted during the last three days of each feeding regimen. The study showed that (1) there was marked hydrolysis of formula fat in the stomach during feeding of either medium-chain triglyceride formula or long-chain triglyceride formula (20% and 16%, respectively); (2) lipase activity in the gastric aspirates was less during feeding of medium-chain triglyceride formula than before the meal, which suggested stimulation of lipase secretion by long-chain fatty acid released from long-chain triglyceride formula fat or more rapid binding of lipase to ingested lipid in the medium-chain triglyceride formula; (3) fatty acid distribution in glycerides and free fatty acids showed preferential release of medium-chain (8:0, 10:0) and long-chain unsaturated (18:1, 18:2) fatty acids in the stomach. The low content of 8:0 and 10:0 in gastric triglyceride and free fatty acids suggested that medium-chain fatty acids were absorbed directly in the stomach. (4) fat balance studies showed almost identical absorption rates (84.6% ± 3.1% and 82.8% ± 4.0%) and weight gain (23.0 ± 1.5 g/d and 20.8 ± 1.8 g/d) during feeding of either medium-chain triglyceride or long-chain triglyceride formula. In this study, in which each infant was fed either formula alternately, it was shown that although the extent of fat digestion varied among infants, medium-chain and long-chain triglyceride were absorbed to the same extent by most infants.


2020 ◽  
Vol 11 ◽  
Author(s):  
Alexandre Umpierrez Amaral ◽  
Moacir Wajner

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.


1999 ◽  
Vol 69 (3) ◽  
pp. 539-543 ◽  
Author(s):  
Jean-Michel Liet ◽  
Hugues Piloquet ◽  
Julio S Marchini ◽  
Pascale Maugère ◽  
Christine Bobin ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Angela Poff ◽  
Andrew Koutnik ◽  
Sara Moss ◽  
Sahith Mandala ◽  
Dominic D'Agostino

Abstract Objectives 70.7% of Americans over 20 years of age are overweight or obese. Currently, the main strategy for weight loss is caloric restriction. Ketone bodies have been shown to facilitate voluntary caloric restriction through altering the appetite stimulating hormone ghrelin. However, these non-toxic ketone bodies have not been evaluated as weight loss supplements. C57BL6J mice were used to determine the weight loss efficacy of exogenous ketones by adding synthetic (R/S 1,3-Butanediol Acetoacetate Diester and 1,3-Butanediol) and natural (Beta-hydroxybutyrate and Beta-hydroxybutyrate + Medium Chain Triglycerides) ketogenic agents to standard rodent chow ab-libitum. Methods Six groups (R/S 1,3-butanediol acetoacetate diester, 1,3-butanediol, beta-hydroxybutyrate, beta-hydroxybutyrate + medium chain triglycerides, caloric restriction, standard diet ad-libitum) were housed 2–5 animals per cage and monitored to ensure appropriate acclimation prior to intervention. Mice were treated for two weeks with ketogenic agents, adjusting % of agent daily to ensure 20% weight loss was achieved. Results All ketogenic agents induced weight loss and voluntary caloric restriction. Weight loss for beta-hydroxybutyrate and beta-hydroxybutyrate + medium chain triglycerides was explained by caloric restriction alone. However, R/S 1,3-butanediol acetoacetate diester induced weight loss at lower dosages which could not be explained by caloric restriction alone. Conclusions Taken together, all ketogenic agents may assist in weight loss. However, R/S 1,3-butanediol acetoacetate diester appears to be a more potent non-toxic ketogenic supplement that facilitates weight loss via both voluntary caloric restriction and caloric restriction-independent mechanisms. Future studies should explore caloric-restriction independent weight loss mechanisms of R/S 1,3-butanediol acetoacetate diester. Funding Sources Disruptive Nutrition.


Metabolism ◽  
1994 ◽  
Vol 43 (10) ◽  
pp. 1287-1292 ◽  
Author(s):  
V.P. Carnielli ◽  
E.J. Sulkers ◽  
C. Moretti ◽  
J.L.D. Wattimena ◽  
J.B. van Goudoever ◽  
...  

1985 ◽  
Vol 249 (2) ◽  
pp. E175-E182
Author(s):  
B. Beaufrere ◽  
P. Tessari ◽  
M. Cattalini ◽  
J. Miles ◽  
M. W. Haymond

A potential effector of the protein-sparing adaptation to fasting could be the increased availability of endogenous long-chain fatty acids. Were this hypothesis correct, infusion of medium-chain triglycerides to increase the plasma concentration of medium-chain fatty acids might also result in protein sparing. However, in most in vitro studies in rat muscle, octanoate increases the oxidation of the essential amino acid leucine. Therefore leucine metabolism was assessed with infusions of [3H]leucine and a-[14C]ketoisocaproate ([14C]KIC) before and during an infusion of trioctanoin in conscious dogs. Plasma octanoate increased from less than 30 to 528 microM over the 3 h of infusion. Plasma leucine and KIC concentrations decreased by 65-70% (P less than 0.01) over the first 2 h of infusion. Leucine oxidation, estimated from the expired 14CO2 and the plasma [14C]KIC specific activity, as well as from an open two-pool model, decreased. By use of these isotope models, the rates of leucine coming from and going to protein decreased (P less than 0.05 to P less than 0.01). Interconversion of leucine and KIC estimated from the open two-pool model decreased by 80% (P less than 0.01). These changes were accompanied by a 36% decrease in the plasma concentration of total plasma amino acids. Within the confines of the isotope models employed, these data are consistent with the hypothesis that increased fatty acid oxidation decreases protein turnover and may spare essential amino acids.


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