scholarly journals Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats

2020 ◽  
Vol 318 (2) ◽  
pp. E216-E223 ◽  
Author(s):  
Robert W. McGarrah ◽  
Guo-Fang Zhang ◽  
Bridgette A. Christopher ◽  
Yann Deleye ◽  
Jacquelyn M. Walejko ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Transporter ◽  
Heart Tissue ◽  
Chow Diet ◽  
Restricted Diet ◽  
Hexokinase Ii ◽  
Acetyl Coa ◽  
Heart Metabolism ◽  
Branched Chain ◽  
The Impact

Elevations in circulating levels of branched-chain amino acids (BCAAs) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAAs in rodent models of obesity lowers circulating BCAA levels and improves whole-animal and skeletal-muscle insulin sensitivity and lipid homeostasis, but the impact of BCAA supply on heart metabolism has not been studied. Here, we report that feeding a BCAA-restricted chow diet to Zucker fatty rats (ZFRs) causes a shift in cardiac fuel metabolism that favors fatty acid relative to glucose catabolism. This is illustrated by an increase in labeling of acetyl-CoA from [1-13C]palmitate and a decrease in labeling of acetyl-CoA and malonyl-CoA from [U-13C]glucose, accompanied by a decrease in cardiac hexokinase II and glucose transporter 4 protein levels. Metabolomic profiling of heart tissue supports these findings by demonstrating an increase in levels of a host of fatty-acid-derived metabolites in hearts from ZFRs and Zucker lean rats (ZLRs) fed the BCAA-restricted diet. In addition, the twofold increase in cardiac triglyceride stores in ZFRs compared with ZLRs fed on chow diet is eliminated in ZFRs fed on the BCAA-restricted diet. Finally, the enzymatic activity of branched-chain ketoacid dehydrogenase (BCKDH) is not influenced by BCAA restriction, and levels of BCAA in the heart instead reflect their levels in circulation. In summary, reducing BCAA supply in obesity improves cardiac metabolic health by a mechanism independent of alterations in BCKDH activity.

scholarly journals Branched-chain fatty acid composition of human milk and the impact of maternal diet: the Global Exploration of Human Milk (GEHM) Study

2016 ◽  
Vol 105 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Kelly A Dingess ◽  
Christina J Valentine ◽  
Nicholas J Ollberding ◽  
Barbara S Davidson ◽  
Jessica G Woo ◽  
...  
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Human Milk ◽  
Acid Composition ◽  
Maternal Diet ◽  
Chain Fatty Acid ◽  
Branched Chain ◽  
The Impact

Abstract 102: Time-of-intake Regulates Glucocorticoid Pharmacology Of Cardiac Bioenergetics

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mattia Quattrocelli ◽  
Michelle Wintzinger ◽  
Karen Miz
Keyword(s):  
Ex Vivo ◽  
Gene Knockout ◽  
Heart Tissue ◽  
Functional Coupling ◽  
Specific Gene ◽  
Heart Metabolism ◽  
Respiratory Capacity ◽  
Circadian Time ◽  
The Impact ◽  
Mitochondrial Respiratory

Glucocorticoid steroids are circadian regulators of energy balance. However, the specific direct effects of glucocorticoids on heart metabolism remain unresolved. Moreover, the impact of circadian time-of-intake on glucocorticoid pharmacology is still unknown. Here, we investigated whether circadian time of exposure gates the effects of synthetic glucocorticoids on heart bioenergetics. We compared the effects of diurnal versus nocturnal glucocorticoids in heart tissue and mitochondria from wildtype mice, controlling the subjective circadian time of drug injection. To avoid interferences from other tissues, we developed an ex vivo system to interrogate the mitochondrial respiratory capacity rate (state III/state IV) in isolated hearts. We found that diurnal but not nocturnal pulse of the glucocorticoid prednisone increased the mitochondrial respiratory capacity rate in heart. This correlated with circadian-restricted effects on mitochondrial abundance. This was remarkable as it contrasts the circadian fluctuations of endogenous glucocorticoids. Using transgenic mice with inducible cardiac-specific gene knockout, we found that the bioenergetic effects of diurnal-restricted prednisone were dependent on the glucocorticoid receptor and its co-factor Kruppel-like factor 15. Considering the bioenergetic decline that hallmarks the aging heart, we asked whether these circadian-gated effects were applicable to aged mice. We therefore treated 24 months-old mice for 12 weeks with a diurnal-restricted regimen of prednisone. Compared to vehicle, diurnal prednisone increased mitochondrial respiration along with NAD + and ATP content in aged hearts. Moreover, lipidomic profiling of myocardial tissue showed that the vast majority of lipids were downregulated after treatment, including triacylglycerols, suggesting a functional coupling between lipid utilization and mitochondrial oxidation in treated hearts. We also found that diurnal-restricted prednisone rescued bioenergetics and improved function in diabetic hearts from db/db mice. In summary, our data indicate that glucocorticoids regulate cardiac bioenergetics according to circadian-time of intake, supporting a role for chrono-pharmacology in aged and diabetic hearts.

scholarly journals The Protective Role of Sestrin2 in High Fat Diet-Induced Nephropathy

2020 ◽  
Author(s):  
Abdelali Agouni ◽  
Duck Y Lee ◽  
Assaad A Eid ◽  
Yves Gorin ◽  
Kumar Sharma
Keyword(s):  
Fatty Acid ◽  
Mouse Model ◽  
High Fat Diet ◽  
Chow Diet ◽  
Pathological Feature ◽  
Lipid Uptake ◽  
Wild Type ◽  
High Fat ◽  
Obesity And Diabetes ◽  
The Impact

Introduction: Obesity is a major risk factor for type-2 diabetes predisposing patients to diabetic nephropathy (DN), the leading cause of end-stage renal failure. Glomerular injury is a prominent pathological feature of DN. Sestrin2 (Sesn2) is a stress-induced protein, but its role in DN has not been investigated. Therefore, we have determined the impact of Sesn2 deletion in a mouse model of obesityinduced nephropathy. Materials and methods: We examined the effects of Sesn2-deficiency in a longterm (22 weeks) mouse model of high fat diet (HFD)-induced obesity on glomerular structure. The severity of renal injury and fibrosis in wild type (Sesn2+/+) mice (fed HFD or chow diets) was compared to that in Sesn2-deficient mice (Sesn2-/- ) fed HFD or chow diets. Animal work was carried out under an IACUC-approved protocol. Results: Data showed that Sesn2 ablation exacerbated HFD-induced glomerular fibrotic injury as evidenced by mesangial matrix hypertrophy and accumulation of both fibronectin and collagen IV. Western blot analysis revealed that HFD- or chow-fed Sesn2-/- mice exhibited higher protein expression of key lipogenic enzymes, fatty acid translocase CD36 (an indicator of lipid uptake), fatty acid synthase and ATP citrate lyase. Sesn2-deficiency in obese mice resulted in podocyte loss as indicated by reduced expression of synaptopodin. Glomerular lesions like those observed in HFD-fed wild-type mice were detected in Sesn2-/-mice fed a chow diet, indicating that the basal deletion of Sesn2 is deleterious by itself. Conclusions: We provide the first evidence that Sesn2 is renoprotective in obesity-induced nephropathy by diminishing lipid accumulation and blocking excessive lipid uptake and de novo lipid synthesis. Understanding the protective of Sesn2 should yield novel therapeutic interventions to effectively preserve glomerular function in obesity and diabetes.

scholarly journals Monomethyl branched-chain fatty acid mediates amino acid sensing by mTORC1

2020 ◽  
Author(s):  
Mengnan Zhu ◽  
Fukang Teng ◽  
Na Li ◽  
Li Zhang ◽  
Jing Shao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Protein Translation ◽  
Postembryonic Development ◽  
Chain Fatty Acid ◽  
Nutrient Sensing ◽  
Acid Deficiency ◽  
Branched Chain ◽  
Amino Acid Sensing ◽  
The Impact

AbstractAnimals have developed various nutrient-sensing mechanisms for survival under fluctuating environments. Although extensive cultured cell-based analyses have discovered diverse mediators of amino acid sensing by mTOR, studies using animal models to illustrate intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid, and downstream glycosphingolipid, that critically mediate overall amino acid sensing by intestinal and neuronal mTORC1 that, in turn, regulates postembryonic development partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may be conserved in mammals. This study uncovers an unexpected amino acid sensing mechanism mediated by a lipid biosynthesis pathway.

Abstract 107: Acetyl-coa Carboxylase 2 Prevents Cardiomyocyte Hypertrophy by Reducing Glucose Reliance

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Julia Ritterhoff ◽  
Dan Shao ◽  
Rong Tian
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cardiac Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
The Impact

In cardiac hypertrophy, the adult heart switches from mainly using fatty acids to increased reliance on glucose to maintain its energetic demands. Reducing fatty acid overload and further increasing glucose reliance has been suggested to be beneficial in the diseased state. Recently, however, it has been shown that increasing fatty acid oxidation (FAO) by cardiac-specific deletion of Acetyl-CoA Carboxylase 2 (ACC2) maintains cardiac energetics and prevents cardiac dysfunction as well as cardiomyocyte hypertrophy during chronic pressure overload. However, it remained unclear, how increased FAO specifically prevented cardiomyocyte hypertrophy. Thus, the goal of this study was to determine the impact of ACC2 deletion on cardiomyocyte hypertrophy in vitro . Adenoviral-mediated knock-down (KD) of ACC2 in adult rat ventricular cardiomyocytes (CMs) resulted in a 70% downregulation of ACC2 mRNA. In standard CM medium (medium M199, 5.5mM glucose) ACC2 KD resulted in a similar increase in CM growth after phenylephrine (PE) treatment as control CMs (+39±10% in control vs. 41±16% in ACC2 KD CMs). Supplementation of 0.4 mM mixed long-chain fatty acids (FA) and 0.1 mU/ml insulin had no effect on cardiomyocyte morphology or hypertrophic response after PE treatment (+42±6%). However, ACC2 KD effectively prevented CM hypertrophy after PE stimulation in the presence of FA/insulin (+9±6%). Whereas PE stimulation in control CMs increased glucose uptake (+28±8%) and reduced fatty acid uptake (-25±6%), both were normalized after ACC2 KD. Inhibiting FAO by etomoxir or increasing glucose utilization by dichloroacetate abolished the beneficial effects of ACC2 KD after PE stimulation. When cultured in glucose-free medium supplemented with FA, ACC2 KD was incapable of preventing cardiomyocyte hypertrophy. Together, these data indicate that increased FAO after ACC2 deletion prevents cardiomyocyte hypertrophy by reducing glucose reliance, suggesting that rather increasing than reducing FAO is beneficial in cardiac hypertrophy.

Relationship of primer specificity of fatty acid de novo synthetase to fatty acid composition in 10 species of bacteria and yeasts

1980 ◽  
Vol 26 (8) ◽  
pp. 893-898 ◽  
Author(s):  
Toshi Kaneda ◽  
E. J. Smith
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Chain Length ◽  
De Novo ◽  
Micrococcus Luteus ◽  
Straight Chain ◽  
Acetyl Coa ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

Fatty acid compositions of lipids from six bacteria and four yeasts were determined. Fatty acid de novo synthetases were investigated with respect to chain length specificity towards acyl-CoA primers of various chain lengths.Four species of bacteria (Bacillus subtilis, Corynebacterium cyclohexanicum, Micrococcus luteus, and Pseudomonas maltophilia) possess branched-chain fatty acids of the iso and anteiso series as the major acids. De novo synthetases from these organisms exhibited specificity towards the chain length of the primer in the order butyrl-CoA > propionyl-CoA [Formula: see text] acetyl-CoA. The remainder, two bacteria and all four yeasts, have the straight-chain type of fatty acids only and fall into two groups: (1) Eschericia coli B, Pseudomonas fluorescens, and Saccharomyces cerevisiae, which utilize the primers in the order acetyl-CoA > propionyl-CoA [Formula: see text] butyryl-CoA; and (2) Candida sake, Candida tropicalis, and Rhodolorula glutinis, which show the order propionyl-CoA > acetyl-CoA [Formula: see text] butyryl-CoA.L-α-Keto-β-methylvalerate, a precursor of the branched-chain primers, can be used as a source of primer for fatty acid synthesis by the organisms with branched-chain acids but not by those with the straight-chain type.The results indicate that organisms having straight-chain fatty acids lack the branched-chain equivalents for two reasons: first, their enzymes are not active toward primers with more than three carbons, and second, they lack a system of supplying suitable branched-chain primers.It appears that activities of de novo synthetases from the organisms having straight-chain fatty acids generally have much higher activities than those from the organisms possessing branched-chain fatty acids.

Evaluation of the Impact of Fatty Acid Methyl Ester (FAME) Contamination on the Thermal Stability of Jet A

2013 ◽  
Author(s):  
Jr Morris ◽  
Shardo Robert W. ◽  
Higgins James ◽  
Cook Kim ◽  
Tanner Rhonda ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Fatty Acid ◽  
Methyl Ester ◽  
Fatty Acid Methyl Ester ◽  
Acid Methyl Ester ◽  
Acid Methyl ◽  
The Impact ◽  
Thermal Stability Of

scholarly journals Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 840
Author(s):  
Jana Ruiz Herrero ◽  
Elvira Cañedo Villarroya ◽  
Luis González Gutiérrez-Solana ◽  
Beatriz García Alcolea ◽  
Begoña Gómez Fernández ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Glucose Transporter ◽  
Deficiency Syndrome ◽  
Laboratory Assessment ◽  
Modified Atkins Diet ◽  
Atkins Diet ◽  
Glut1 Deficiency ◽  
Glut1 Deficiency Syndrome ◽  
The Impact

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. Methods: An observational descriptive study was conducted to describe 18 children (January 2009–August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. Results: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. Conclusions: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

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