scholarly journals Serum Branch Chain Amino Acids (BCAAs) Are Elevated Due to Decreased Catabolism in Patients With Ketosis-Prone Diabetes at the Time of Presentation With DKA

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A430-A430
Author(s):  
Jean Wei Hsu ◽  
Paras Bharatesh Mehta ◽  
Nupur Kikani ◽  
Kelly Keene ◽  
Ruchi Gaba ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Energy Production ◽  
Cell Function ◽  
Acetyl Coa ◽  
Emergency Center ◽  
Catabolic Enzymes ◽  
Keto Acids ◽  
Branch Chain Amino ◽  
Time Of Presentation ◽  
And Control

Abstract Patients with “A-β+” Ketosis-Prone Diabetes (KPD) develop diabetic ketoacidosis (DKA) despite lacking islet autoantibodies and a phenotype of T1D, have good beta cell function and can come off insulin therapy 4–8 weeks after the DKA episode. When near-normoglycemic and stable on metformin, they have accelerated BCAA catabolism which promotes ketogenesis (Patel SG et al, Diabetes 2013). Here we measured BCAAs, their metabolites and acylcarnitine esters (C5,C3) in blood samples obtained from adults with DKA (N=74) compared to those with non-ketotic hyperglycemic crisis (N=21) at the time of acute presentation to the emergency center, and to healthy controls (N=17). Of the DKA patients, 53 were classified as likely A-β+ KPD based on absence of GAD65Ab and C-peptide levels or clinical features, and the 21 patients with non-ketotic hyperglycemia were classified as T2D. Serum concentrations of leucine, isoleucine and valine and their respective branch chain keto acids (BCKA) were higher (p<0.05) in KPD patients compared to T2D and control. The ratio of each BCKA to its precursor BCAA was calculated as an index of its rate of transamination. Serum KIC/Leu, KMV/Ile and KIV/Val were significantly lower (p<0.05) in KPD compared to T2D. The ratio of each acylcarnitine to its precursor BCKA was calculated as an index of its rate of entry and metabolism within mitochondria. Serum C5/KIC, C5/KMV and C5/KIC+KMV were lower (p<0.05) in KPD patients compared to T2D patients. Serum C3/KIV, C3/KMV and C3/KIV+KMV were significantly lower (p<0.05) in KPD patients compared to controls. Since KIC can be converted to acetoacetate and then reduced to β-hydroxybutyrate (BHOB), and KIC and KMV can be metabolized to acetyl CoA, the ratios of KIC+KMV/C2 and KIC/BHOB were calculated as indicators of their relative conversion to acetyl CoA and acetoacetate respectively. KIC+KMV/C2 was significantly lower (p<0.001) in KPD than T2D and control and KIC/BOHB was lower (p<0.001) in KPD than T2D. Acetyl carnitine was markedly elevated in the KPD group, indicating accelerated production of acetyl CoA from free fatty acids. During acute DKA, KPD patients have higher serum BCAAs because their catabolism is decreased, due to slower rate of transamination in the cytosol by BCAA transaminase 1 (BCAT1) and slower rate of entry into mitochondria and metabolism to acetyl CoA and acetoacetate by BCAT2, BCKA dehydrogenase and other catabolic enzymes. This is diametrically opposite to their profile in the stable, near-normoglycemic state, when BCAA catabolism is accelerated. We propose that during acute DKA, accelerated flux of fatty acids to acetyl CoA diminishes carnitine and NAD+ availability for mitochondrial transport and metabolism of BCAA catabolites in KPD patients, whereas in the near-normoglycemic state they have heightened dependence on BCAA catabolism for energy production through acetyl CoA and ketogenesis.

scholarly journals Short Chain Fatty Acids Outpace Ketone Oxidation in the Failing Heart

Circulation ◽  
2021 ◽  
Author(s):  
Andrew N. Carley ◽  
Santosh K. Maurya ◽  
Matthew Fasano ◽  
Yang Wang ◽  
Craig H. Selzman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Carbon Source ◽  
Energy Production ◽  
Tricarboxylic Acid Cycle ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Sham Operation ◽  
Acetyl Coa ◽  
Failing Heart ◽  
Chain Fatty Acids

Background: The failing heart is energy-starved with impaired oxidation of long chain fatty acids (LCFA) at the level of reduced carnitine palmitoyltransferase 1 (CPT1) activity at the outer mitochondrial membrane. Recent work shows elevated ketone oxidation in failing hearts as an alternate carbon source for oxidative ATP generation. We hypothesized that another short chain carbon source, short chain fatty acids (SCFA) that bypass CPT1, could similarly support energy production in failing hearts. Methods: Cardiac hypertrophy and dysfunction was induced in rats by transverse-aortic constriction (TAC). 14 weeks after TAC or sham-operation, isolated hearts were perfused with either the four carbon, 13 C-labeled ketone (D3-hydroxybutyrate) or the four carbon, 13 C -labeled SCFA, butyrate in the presence of glucose and the LCFA, palmitate. Oxidation of ketone and SCFA was compared by in vitro 13 C NMR spectroscopy, as was the capacity for short chain carbon sources to compensate for impaired LCFA oxidation in the hypertrophic heart. Adaptive changes in enzyme expression and content for the distinct pathways of ketone and SCFA oxidation were examined in both failing rat and human hearts. Results: TAC produced pathological hypertrophy and increased the fractional contributions of ketone to acetyl CoA production in the tricarboxylic acid cycle (0.60±0.02 sham ketone vs 0.70±0.02 TAC ketone, p<0.05). However, butyrate oxidation in failing hearts was 15% greater (0.803±0.02 TAC SCFA) than ketone oxidation. SCFA was also more readily oxidized than ketone in sham hearts by 15% (0.693±0.02 sham SCFA). Despite greater SFCA oxidation, TAC did not change short chain acyl CoA dehydrogenase content. However, failing hearts of humans and the rat model both contain significant increases in acyl CoA synthetase medium chain 3 enzyme gene expression and protein content. The increased oxidation of SCFA and ketones occurred at the expense of LCFA oxidation, with LCFA contributing less to acetyl CoA production in failing hearts perfused with SCFA (0.19±0.012 TAC SCFA vs. 0.3163±0.036 TAC ketone). Conclusions: SCFA are more readily oxidized than ketones in failing hearts, despite both bypassing reduced CPT1 activity, and represents an unexplored carbon source for energy production in failing hearts.

The Relationship of Fasting Free Fatty Acids, Adipose Tissue, Insulin Resistance, and Fasting Glucose Concentrations with Subsequent ß-Cell Function in Nondiabetic Subjects

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1812-P
Author(s):  
MARIA D. HURTADO ◽  
J.D. ADAMS ◽  
MARCELLO C. LAURENTI ◽  
CHIARA DALLA MAN ◽  
CLAUDIO COBELLI ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Fasting Glucose ◽  
Relationship Of ◽  
The Relationship

N-3 Polyunsaturated Fatty Acids Modulate In-Vitro T Cell Function in Type I Diabetic Patients

Lipids ◽  
2008 ◽  
Vol 43 (6) ◽  
pp. 485-497 ◽  
Author(s):  
Sid Ahmed Merzouk ◽  
Meriem Saker ◽  
Karima Briksi Reguig ◽  
Nassima Soulimane ◽  
Hafida Merzouk ◽  
...  
Keyword(s):  
Fatty Acids ◽  
T Cell ◽  
Polyunsaturated Fatty Acids ◽  
Cell Function ◽  
Diabetic Patients ◽  
Type I ◽  
T Cell Function

scholarly journals Optimization of Low Head Axial-Flow Turbines for an Overtopping BReakwater for Energy Conversion: A Case Study

Energies ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4618
Author(s):  
Antonio Mariani ◽  
Gaetano Crispino ◽  
Pasquale Contestabile ◽  
Furio Cascetta ◽  
Corrado Gisonni ◽  
...  
Keyword(s):  
Energy Conversion ◽  
Control Strategy ◽  
Energy Production ◽  
San Antonio ◽  
Axial Flow ◽  
Complex Process ◽  
Low Head ◽  
Wave Power Conversion ◽  
And Control

Overtopping-type wave power conversion devices represent one of the most promising technology to combine reliability and competitively priced electricity supplies from waves. While satisfactory hydraulic and structural performance have been achieved, the selection of the hydraulic turbines and their regulation is a complex process due to the very low head and a variable flow rate in the overtopping breakwater set-ups. Based on the experience acquired on the first Overtopping BReakwater for Energy Conversion (OBREC) prototype, operating since 2016, an activity has been carried out to select the most appropriate turbine dimension and control strategy for such applications. An example of this multivariable approach is provided and illustrated through a case study in the San Antonio Port, along the central coast of Chile. In this site the deployment of a breakwater equipped with OBREC modules is specifically investigated. Axial-flow turbines of different runner diameter are compared, proposing the optimal ramp height and turbine control strategy for maximizing system energy production. The energy production ranges from 20.5 MWh/y for the smallest runner diameter to a maximum of 34.8 MWh/y for the largest runner diameter.

Evaluation of weed control in acetyl coA carboxylase-resistant rice with mixtures of quizalofop and auxinic herbicides

2019 ◽  
Vol 34 (4) ◽  
pp. 498-505
Author(s):  
Tameka L. Sanders ◽  
Jason A. Bond ◽  
Benjamin H. Lawrence ◽  
Bobby R. Golden ◽  
Thomas W. Allen ◽  
...  
Keyword(s):  
Weed Control ◽  
Rice Yield ◽  
Field Studies ◽  
Growth Stages ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Herbicide Treatments ◽  
Herbicide Mixture ◽  
Sequential Treatments ◽  
And Control

AbstractRice with enhanced tolerance to herbicides that inhibit acetyl coA carboxylase (ACCase) allows POST application of quizalofop, an ACCase-inhibiting herbicide. Two concurrent field studies were conducted in 2017 and 2018 near Stoneville, MS, to evaluate control of grass (Grass Study) and broadleaf (Broadleaf Study) weeds with sequential applications of quizalofop alone and in mixtures with auxinic herbicides applied in the first or second application. Sequential treatments of quizalofop were applied at 119 g ai ha−1 alone and in mixtures with labeled rates of auxinic herbicides to rice at the two- to three-leaf (EPOST) or four-leaf to one-tiller (LPOST) growth stages. In the Grass Study, no differences in rice injury or control of volunteer rice (‘CL151’ and ‘Rex’) were detected 14 and 28 d after last application (DA-LPOST). Barnyardgrass control at 14 and 28 DA-LPOST with quizalofop applied alone or with auxinic herbicides EPOST was ≥93% for all auxinic herbicide treatments except penoxsulam plus triclopyr. Barnyardgrass control was ≥96% with quizalofop applied alone and with auxinic herbicides LPOST. In the Broadleaf Study, quizalofop plus florpyrauxifen-benzyl controlled more Palmer amaranth 14 DA-LPOST than other mixtures with auxinic herbicides, and control with this treatment was greater EPOST compared with LPOST. Hemp sesbania control 14 DA-LPOST was ≤90% with quizalofop plus quinclorac LPOST, orthosulfamuron plus quinclorac LPOST, and triclopyr EPOST or LPOST. All mixtures except quinclorac and orthosulfamuron plus quinclorac LPOST controlled ivyleaf morningglory ≥91% 14 DA-LPOST. Florpyrauxifen-benzyl or triclopyr were required for volunteer soybean control >63% 14 DA-LPOST. To optimize barnyardgrass control and rice yield, penoxsulam plus triclopyr and orthosulfamuron plus quinclorac should not be mixed with quizalofop. Quizalofop mixtures with auxinic herbicides are safe and effective for controlling barnyardgrass, volunteer rice, and broadleaf weeds in ACCase-resistant rice, and the choice of herbicide mixture could be adjusted based on weed spectrum in the treated field.

Quantitative Changes of the Lipid and Fatty Acid Composition of Leaves of Aleurites montana as a Consequence of Growth under 700 ppm CO2 in the Atmosphere

1996 ◽  
Vol 51 (11-12) ◽  
pp. 833-840 ◽  
Author(s):  
P He ◽  
A Radunz ◽  
K. P Bader ◽  
G. H Schmid
Keyword(s):  
Fatty Acids ◽  
Thylakoid Membrane ◽  
Saturated Fatty Acids ◽  
Phospholipid Fraction ◽  
Phospholipid Content ◽  
The Core ◽  
Glycolipid Fraction ◽  
Carbonic Acids ◽  
And Control ◽  
Β Carotene

Abstract Leaf lipids of Aleurites plants that were cultivated for 5 months in air containing 700 ppm CO2, were compared to those of control plants cultivated at 350 ppm CO2. The content of ether soluble lipids referred to dry matter is the same in CO2-and control plants. The comparison of lipids analyzed as the pigments chlorophyll and carotenoids, phospholipids and glycolipids shows that the ratio of phospholipids and glycolipids is slightly shifted in favor of phospholipids in CO2-plants. Thus, within the group of phospholipids, phosphatidylglycerol and phosphatidylinositol occur in higher concentrations in CO2-plants. Although the differences in the lipid content appear moderate in CO2-and control plants, it is the saturation degree of fatty acids that differs substantially. The fatty acids of CO2-plants contain according to the higher phospholipid content approx. 5% more saturated fatty acids. Stearic acid is three-fold increased. Whereas in the phospholipid fraction saturated fatty acids comprise one half of all fatty acids, the unsaturated fatty acids make up for 80 to 90% in the glycolipid fraction. In CO2-plants not only in the phospholipid fraction but also in the glycolipid fraction saturated fatty acids occur in a higher portion. This means that not only in the cell membrane of CO2-plants but also in the thylakoid membrane the fluidity is decreased. Also in the wax-fraction long-chained carbonic acids with 20 -26 carbon atoms occur. As the portion of these carbonic acids is twice as high in CO2-plants, it is concluded that a stronger formation of the wax layers exists in CO2-plants. By means of Western blotting and by the use of lipid and carotenoid antisera the binding of lipids onto proteins of photosystem II and photosystem I was analyzed. It is seen that besides the major amount of lipids which build up the thylakoid membrane, some lipids are also bound to membrane peptides. Whereas monogalactolipid is bound to the LHCP-complex peptides, to the OEC1 -peptide and the 43 and 47 kDa chlorophyll binding peptides, the anionic lipids sulfoquinovosyldiglyceride and phosphatidylglycerol and digalactolipid are bound to the core peptides of PS II and PS I. β-carotene and the xanthophylls were found to be bound to the core peptides and β-carotene and violaxanthin were also bound to the light-harvesting pigment complex.

scholarly journals Cellular and metabolic mechanisms of nutrient actions in immune function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Vitamin D ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Structure ◽  
Nutritional Intervention ◽  
Immune Cell Function ◽  
And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

Effects of cold acclimation on lipid metabolism in adipose tissue

1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cold Acclimation ◽  
Long Chain Fatty Acids ◽  
Synthetic Capacity ◽  
And Control ◽  
Long Chain ◽  
Chain Fatty Acids

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.

scholarly journals Effects of propionate and carnitine on the hepatic oxidation of short- and medium-chain-length fatty acids

1988 ◽  
Vol 250 (3) ◽  
pp. 819-825 ◽  
Author(s):  
E P Brass ◽  
R A Beyerinck
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Organic Acid ◽  
Chain Length ◽  
Ketone Body ◽  
Acetyl Coa ◽  
Body Formation ◽  
Medium Chain ◽  
Medium Chain Length ◽  
Hepatic Oxidation

Accumulation of propionate, or its metabolic product propionyl-CoA, can disrupt normal cellular metabolism. The present study examined the effects of propionate, or propionyl-CoA generated during the oxidation of odd-chain-length fatty acids, on hepatic oxidation of short- and medium-chain-length fatty acids. In isolated hepatocytes, ketone-body formation from odd-chain-length fatty acids was slow as compared with even-chain-length fatty acid substrates, and increased as the carbon chain length was increased from five to seven to nine. In contrast, rates of ketogenesis from butyrate, hexonoate and octanoate were all approximately equal. Propionate (10 mM) inhibited ketogenesis from butyrate, hexanoate and octanoate by 81%, 53% and 18% respectively. Addition of carnitine had no effect on ketogenesis from the even-chain-length fatty acids, but increased the rate of ketone-body formation from pentanoate (by 53%), heptanoate (by 28%) and from butyrate or hexanoate in the presence of propionate. The inhibitory effect of propionate could not be explained by shunting acetyl-CoA into the tricarboxylic acid cycle, as CO2 formation from butyrate was also decreased by propionate. Examination of the hepatocyte CoA pool during oxidation of butyrate demonstrated that addition of propionate decreased acetyl-CoA and CoA as propionyl-CoA accumulated. Addition of carnitine decreased propionyl-CoA by 50% (associated with production of propionylcarnitine) and increased acetyl-CoA and CoA. Similar changes in the CoA pool were seen during the oxidation of pentanoate. These results demonstrate that accumulation of propionyl-CoA results in inhibition of short-chain fatty acid oxidation. Carnitine can partially reverse this inhibition. Changes in the hepatocyte CoA pool are consistent with carnitine acting by generating propionylcarnitine, thereby decreasing propionyl-CoA and increasing availability of free CoA. The data provide further evidence of the potential cellular toxicity from organic acid accretion, and supports the concept that carnitine's interaction with the cellular CoA pool can have a beneficial effect on cellular metabolism and function under conditions of unusual organic acid accumulation.

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