The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
William E Kraus - One of the best experts on this subject based on the ideXlab platform.
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validation of the association between a branched chain Amino Acid Metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization
Atherosclerosis, 2014Co-Authors: Sayanti Bhattacharya, Christopher B Granger, Damian M Craig, Carol Haynes, James R Bain, Robert Stevens, Elizabeth R Hauser, Christopher B Newgard, William E KrausAbstract:Objective To validate independent associations between branched-chain Amino Acids (BCAA) and other Metabolites with coronary artery disease (CAD).
Christopher B Granger - One of the best experts on this subject based on the ideXlab platform.
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validation of the association between a branched chain Amino Acid Metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization
Atherosclerosis, 2014Co-Authors: Sayanti Bhattacharya, Christopher B Granger, Damian M Craig, Carol Haynes, James R Bain, Robert Stevens, Elizabeth R Hauser, Christopher B Newgard, William E KrausAbstract:Objective To validate independent associations between branched-chain Amino Acids (BCAA) and other Metabolites with coronary artery disease (CAD).
Cholsoon Jang - One of the best experts on this subject based on the ideXlab platform.
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a branched chain Amino Acid Metabolite drives vascular fatty Acid transport and causes insulin resistance
Nature Medicine, 2016Co-Authors: Cholsoon Jang, Sungwhan F Oh, Shogo Wada, Glenn C Rowe, Mun Chun Chan, James Rhee, Atsushi HoshinoAbstract:Fatty Acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain Amino Acid Metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain Amino Acids and diabetes.
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A branched-chain Amino Acid Metabolite drives vascular fatty Acid transport and causes insulin resistance
Nature Medicine, 2016Co-Authors: Cholsoon Jang, Sungwhan F Oh, Shogo Wada, Glenn C Rowe, Mun Chun Chan, James Rhee, Atsushi Hoshino, Ayon Ibrahim, Luisa G Baca, Chandra C GhoshAbstract:Fatty Acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain Amino Acid Metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain Amino Acids and diabetes. Epidemiological and experimental data implicate branched-chain Amino Acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear^ 1 , 2 , 3 . Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species^ 4 , a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a ), a transcriptional coactivator that regulates broad programs of fatty Acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty Acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty Acid transport, stimulates muscle fatty Acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty Acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the Metabolite 3-HIB, by regulating the trans-endothelial flux of fatty Acids, links the regulation of fatty Acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
K K Mcfadden - One of the best experts on this subject based on the ideXlab platform.
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maternal restricted and over feeding during gestation result in distinct lipid and Amino Acid Metabolite profiles in the longissimus muscle of the offspring
Frontiers in Physiology, 2019Co-Authors: Dominique E Martin, A K Jones, Sambhu M Pillai, M L Hoffman, K K McfaddenAbstract:: Maternal over- and restricted-feeding during gestation have similar negative consequences for the offspring, including decreased muscularity, increased adiposity, and altered metabolism. Our objective was to determine the effects of poor maternal nutrition during gestation (over- and restricted-feeding) on the offspring muscle Metabolite profile. Pregnant ewes (n = 47) were fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at day 30.2 ± 0.2 of gestation. Offspring sample collection occurred at days 90 and 135 of gestation, and within 24 h of birth. C2C12 myoblasts were cultured in serum collected from offspring at birth (n = 18; 6 offspring per treatment) for analysis of oxidative and glycolytic capacity. Unbiased Metabolite analysis of longissimus muscle samples (n = 72; 8 fetuses per treatment per time point) was performed using mass spectrometry. Data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. Cells cultured in serum from RES offspring exhibited increased proton leak 49% (p = 0.01) compared with CON, but no other variables of mitochondrial respiration or glycolytic function were altered. Mass spectrometry identified 612 Metabolites. Principle component analysis identified day of gestation as the primary driver of metabolic change; however, maternal diet also altered the lipid and Amino Acid profiles in offspring. The abundance of 53 Amino Acid Metabolites and 89 lipid Metabolites was altered in RES compared with CON (p ≤ 0.05), including phospholipids, sphingolipids, and ceramides within the lipid metabolism pathway and Metabolites involved in glutamate, histidine, and glutathione metabolism. Similarly, abundance of 63 Amino Acid Metabolites and 70 lipid Metabolites was altered in OVER compared with CON (p ≤ 0.05). These include Metabolites involved in glutamate, histidine, lysine, and tryptophan metabolism and phosphatidylethanolamine, lysophospholipids, and fatty Acids involved in lipid metabolism. Further, the Amino Acid and lipid profiles diverged between RES and OVER, with 69 Amino Acid and 118 lipid Metabolites differing (p ≤ 0.05) between groups. Therefore, maternal diet affects Metabolite abundance in offspring longissimus muscle, specifically Metabolites involved in lipid and Amino metabolism. These changes may impact post-natal skeletal muscle metabolism, possibly altering energy efficiency and long-term health.
Atsushi Hoshino - One of the best experts on this subject based on the ideXlab platform.
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a branched chain Amino Acid Metabolite drives vascular fatty Acid transport and causes insulin resistance
Nature Medicine, 2016Co-Authors: Cholsoon Jang, Sungwhan F Oh, Shogo Wada, Glenn C Rowe, Mun Chun Chan, James Rhee, Atsushi HoshinoAbstract:Fatty Acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain Amino Acid Metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain Amino Acids and diabetes.
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A branched-chain Amino Acid Metabolite drives vascular fatty Acid transport and causes insulin resistance
Nature Medicine, 2016Co-Authors: Cholsoon Jang, Sungwhan F Oh, Shogo Wada, Glenn C Rowe, Mun Chun Chan, James Rhee, Atsushi Hoshino, Ayon Ibrahim, Luisa G Baca, Chandra C GhoshAbstract:Fatty Acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain Amino Acid Metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain Amino Acids and diabetes. Epidemiological and experimental data implicate branched-chain Amino Acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear^ 1 , 2 , 3 . Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species^ 4 , a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1α; encoded by Ppargc1a ), a transcriptional coactivator that regulates broad programs of fatty Acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty Acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty Acid transport, stimulates muscle fatty Acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1α to promote endothelial fatty Acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the Metabolite 3-HIB, by regulating the trans-endothelial flux of fatty Acids, links the regulation of fatty Acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
