scholarly journals Intrinsic Mitochondrial Nutrient Utilization May Underlie the Association of Metabolite Levels with BMIz and Insulin Resistance (FS03-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jennifer LaBarre ◽  
Karen Peterson ◽  
Wei Hao ◽  
Maureen Kachman ◽  
Lu Tang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Positive Association ◽  
Nutrient Utilization ◽  
Macronutrient Intake ◽  
C Peptide ◽  
Medium Chain ◽  
The Relationship

Abstract Objectives To identify metabolites associated with BMIz and insulin resistance (IR) among 108 girls and 98 boys aged 8–14 years. We sought evidence of whether altered mitochondrial nutrient utilization, as indicated by mitochondrial-derived metabolites, mediates the relationship between diet, IR and obesity. Methods Anthropometry, fasting untargeted-liquid chromatography/mass spectrometry-derived metabolites and C-Peptide, and semi-quantitative food frequency questionnaires were collected from adolescents in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort. Sex-stratified generalized linear models were used to identify metabolites that are marginally associated BMIz and HOMA C-peptide (HOMA-CP), accounting for puberty, age and muscle and fat area (FDR < 0.1). Assessed the relationship between energy-adjusted macronutrient intake with HOMA-CP and BMIz. Structural equation models coupled with hierarchical clustering identified clusters of metabolites that may mediate the relationship between macronutrient intake with BMIz and HOMA-CP. Results Stratification by sex demonstrated sex-specific associations with BMIz. Most notable were girl's positive association with diacylglycerols and boy's positive association with branched chain and aromatic amino acids, independent of HOMA-CP. Intermediates in fatty acid metabolism, including medium chain acylcarnitines (acylCN), were inversely associated with HOMA-CP. No direct relationship was observed between macronutrient intake with BMIz and IR. Using mediation analyses, fat intake is positively associated with BMIz and HOMA-CP through increases in levels of dicarboxylic fatty acids (DiC-FA), products of omega-oxidation. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of medium chain acylCN, products of β-oxidation. Conclusions Insulin resistance in children appears to be associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extra-mitochondrial fatty acid metabolism (DiC-FA), while higher carbohydrate intake appears to lead to accumulation of intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake. Funding Sources This work was supported by the NIEHS, EPA and NIDDK.

scholarly journals Mitochondrial Nutrient Utilization Underlying the Association Between Metabolites and Insulin Resistance in Adolescents

2020 ◽  
Vol 105 (7) ◽  
pp. 2442-2455 ◽  
Author(s):  
Jennifer L LaBarre ◽  
Karen E Peterson ◽  
Maureen T Kachman ◽  
Wei Perng ◽  
Lu Tang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Dietary Intake ◽  
Path Analysis ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Health ◽  
Macronutrient Intake ◽  
C Peptide ◽  
The Relationship

Abstract Context A person’s intrinsic metabolism, reflected in the metabolome, may describe the relationship between nutrient intake and metabolic health. Objectives Untargeted metabolomics was used to identify metabolites associated with metabolic health. Path analysis classified how habitual dietary intake influences body mass index z-score (BMIz) and insulin resistance (IR) through changes in the metabolome. Design Data on anthropometry, fasting metabolites, C-peptide, and dietary intake were collected from 108 girls and 98 boys aged 8 to 14 years. Sex-stratified linear regression identified metabolites associated with BMIz and homeostatic model assessment of IR using C-peptide (HOMA-CP), accounting for puberty, age, and muscle and fat area. Path analysis identified clusters of metabolites that underlie the relationship between energy-adjusted macronutrient intake with BMIz and HOMA-CP. Results Metabolites associated with BMIz include positive associations with diglycerides among girls and positive associations with branched chain and aromatic amino acids in boys. Intermediates in fatty acid metabolism, including medium-chain acylcarnitines (AC), were inversely associated with HOMA-CP. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of AC, products of β-oxidation. Approaching significance, fat intake is positively associated with HOMA-CP through increases in levels of dicarboxylic fatty acids, products of omega-oxidation. Conclusions This cross-sectional analysis suggests that IR in children is associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extramitochondrial fatty acid metabolism, while higher carbohydrate intake appears to lead to decreases in intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.

scholarly journals Engineering the Monomer Composition of Polyhydroxyalkanoates Synthesized in Saccharomyces cerevisiae

2006 ◽  
Vol 72 (1) ◽  
pp. 536-543 ◽  
Author(s):  
Bo Zhang ◽  
Ross Carlson ◽  
Friedrich Srienc
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acid ◽  
Chain Length ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Pha Synthase ◽  
Fatty Acid Degradation ◽  
Medium Chain ◽  
Acid Degradation ◽  
Wide Range

ABSTRACT Polyhydroxyalkanoates (PHAs) have received considerable interest as renewable-resource-based, biodegradable, and biocompatible plastics with a wide range of potential applications. We have engineered the synthesis of PHA polymers composed of monomers ranging from 4 to 14 carbon atoms in either the cytosol or the peroxisome of Saccharomyces cerevisiae by harnessing intermediates of fatty acid metabolism. Cytosolic PHA production was supported by establishing in the cytosol critical β-oxidation chemistries which are found natively in peroxisomes. This platform was utilized to supply medium-chain (C6 to C14) PHA precursors from both fatty acid degradation and synthesis to a cytosolically expressed medium-chain-length (mcl) polymerase from Pseudomonas oleovorans. Synthesis of short-chain-length PHAs (scl-PHAs) was established in the peroxisome of a wild-type yeast strain by targeting the Ralstonia eutropha scl polymerase to the peroxisome. This strain, harboring a peroxisomally targeted scl-PHA synthase, accumulated PHA up to approximately 7% of its cell dry weight. These results indicate (i) that S. cerevisiae expressing a cytosolic mcl-PHA polymerase or a peroxisomal scl-PHA synthase can use the 3-hydroxyacyl coenzyme A intermediates from fatty acid metabolism to synthesize PHAs and (ii) that fatty acid degradation is also possible in the cytosol as β-oxidation might not be confined only to the peroxisomes. Polymers of even-numbered, odd-numbered, or a combination of even- and odd-numbered monomers can be controlled by feeding the appropriate substrates. This ability should permit the rational design and synthesis of polymers with desired material properties.

scholarly journals Reply: “Letter to the Editor Re: Billeaud et al. Nutrients 2018, 10, 690”

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 406
Author(s):  
Claude Billeaud ◽  
Carole Boué-Vaysse ◽  
Leslie Couëdelo ◽  
Philippe Steenhout ◽  
Jonathan Jaeger ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Human Milk ◽  
Preterm Infants ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Medium Chain ◽  
Letter To The Editor ◽  
Human Milk Fortifier

We thank Bernard and colleagues for their careful reading and interest in our article Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants [...]

Intracellular Fatty Acid Metabolism in Skeletal Muscle and Insulin Resistance

2005 ◽  
Vol 1 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Eun Koh ◽  
Woo Lee ◽  
Min-Seon Kim ◽  
Joong-Yeol Park ◽  
In Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism

scholarly journals Aberrant fatty acid metabolism in skeletal muscle contributes to insulin resistance in zinc transporter 7 (znt7)-knockout mice

2018 ◽  
Vol 293 (20) ◽  
pp. 7549-7563 ◽  
Author(s):  
Liping Huang ◽  
Surapun Tepaamorndech ◽  
Catherine P. Kirschke ◽  
John W. Newman ◽  
William R. Keyes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Knockout Mice ◽  
Acid Metabolism ◽  
Zinc Transporter

Pcyt2 Deficiency Causes Age-Dependant Development of Non-Alcoholic Steatohepatitis and Insulin Resistance that Could be Attenuated with Phospho-Ethanolamine

2021 ◽  
Author(s):  
Sophie Grapentine ◽  
Rathnesh K. Singh ◽  
Poulami Basu ◽  
Sugashan Sivanesan ◽  
Gabriela Mattos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Therapeutic Potential ◽  
Glucose Production ◽  
Heterozygous Deletion ◽  
Metabolic Dysregulation ◽  
Age Dependent ◽  
Rate Limiting

Abstract The mechanisms of NASH development in the context of age and genetics are not fully elucidated. This study investigates the age-dependent liver defects during NASH development in mice with heterozygous deletion of Pcyt2 (ETKO), the rate limiting enzyme in phosphatidylethanolamine (PE) synthesis. Further, the therapeutic potential of Pcyt2 substrate, phosphoethanolamine (PEtn), is examined. ETKO were investigated at 2, 6 and 8 months of age and in addition, 6-mo old ETKO with developed NASH were supplemented with PEtn for 8 weeks and glucose and fatty acid metabolism, insulin signaling, and inflammation were examined. Heterozygous ablation of Pcyt2 causes specific transcriptional and signaling adaptations in lipid/fatty acids and energy metabolism regulators from young age, prior to the development of liver disease which does not occur until adulthood. Only older ETKO liver experiences perturbed protein, glucose, and fatty acid metabolism. Older ETKO liver develops NASH characterized by increased glucose production, accumulation of TAG and glycogen, and increased insulin resistance and inflammation. Supplementation with PEtn reverses ETKO steatosis, inflammation, and other aspects of NASH, showing that was directly caused by Pcyt2 deficiency. Pcyt2 deficiency is a novel mechanism of metabolic dysregulation due to reduced membrane ethanolamine phospholipid synthesis, and the metabolite PEtn offers therapeutic potential for NASH reversion.

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