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Article ; Online: Isotopomer analyses with the tricarboxylic acid cycle intermediates and exchanging metabolites from the rat kidney.

Jin, Eunsook S / Wen, Xiaodong / Malloy, Craig R

2023 Volume 36, Issue 10, Page(s) e4994

Abstract: Renal metabolism is essential for kidney functions and energy homeostasis in the body. The TCA cycle is the hub of metabolism, but the metabolic activities of the cycle in the kidney have rarely been investigated. This study is to assess metabolic ... ...

Abstract	Renal metabolism is essential for kidney functions and energy homeostasis in the body. The TCA cycle is the hub of metabolism, but the metabolic activities of the cycle in the kidney have rarely been investigated. This study is to assess metabolic processes at the level of the TCA cycle in the kidney based on isotopomer distributions in multiple metabolites. Isolated rat kidneys were perfused with media containing common substrates including lactate and alanine for an hour. One group of kidneys received [U-
MeSH term(s)	Rats ; Animals ; Citric Acid Cycle ; Malates/metabolism ; Pyruvate Carboxylase/metabolism ; Aspartic Acid/metabolism ; Glucose/metabolism ; Glutamic Acid/metabolism ; Pyruvic Acid/metabolism ; Lactic Acid ; Succinates ; Alanine/metabolism ; Carbon Isotopes/metabolism
Chemical Substances	malic acid (817L1N4CKP) ; Malates ; Pyruvate Carboxylase (EC 6.4.1.1) ; Aspartic Acid (30KYC7MIAI) ; Glucose (IY9XDZ35W2) ; Glutamic Acid (3KX376GY7L) ; Pyruvic Acid (8558G7RUTR) ; Lactic Acid (33X04XA5AT) ; Succinates ; Alanine (OF5P57N2ZX) ; Carbon Isotopes
Language	English
Publishing date	2023-07-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4994
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Zs.A 2869: Show issues

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Article ; Online: The presence of 3-hydroxypropionate and 1,3-propanediol suggests an alternative path for conversion of glycerol to Acetyl-CoA.

Jin, Eunsook S / Lee, Min H / Malloy, Craig R

Metabolism open

2021 Volume 9, Page(s) 100086

Abstract: Background: In our recent study using [U-: Methods: Fasted hamsters received acetaminophen (400 mg/kg; n = 16) or saline (n = 10) intraperitoneally. After waiting 2 h, all the animals received [U-: Results: 1,3PDO and 3HP derived from [U-: ... ...

Abstract	Background: In our recent study using [U- Methods: Fasted hamsters received acetaminophen (400 mg/kg; n = 16) or saline (n = 10) intraperitoneally. After waiting 2 h, all the animals received [U- Results: 1,3PDO and 3HP derived from [U- Conclusion: Detection of 1,3PDO and 3HP in the hamster liver was associated with unorthodox metabolism of glycerol characterized by conversion of 3HP to acetyl-CoA followed by ketogenesis and oxidative metabolism through the TCA cycle. Additional mechanistic studies are needed to determine the causes of unusual glycerol metabolism in a subset of these hamsters.
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article
ISSN	2589-9368
ISSN (online)	2589-9368
DOI	10.1016/j.metop.2021.100086
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Article ; Online: 13

Jin, Eunsook S / Lee, Min H / Malloy, Craig R

NMR in biomedicine

2021 Volume 34, Issue 7, Page(s) e4533

Abstract: After administration ... ...

Abstract	After administration of
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Carbon-13 Magnetic Resonance Spectroscopy ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Lactic Acid/metabolism ; Male ; Metabolome ; Myocardium/metabolism ; Pentose Phosphate Pathway ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid/metabolism ; Rats
Chemical Substances	Glutamine (0RH81L854J) ; Lactic Acid (33X04XA5AT) ; Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2021-04-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4533
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Article ; Online: Recent progress in analysis of intermediary metabolism by ex vivo

Malloy, Craig R / Sherry, A Dean / Alger, Jeffry R / Jin, Eunsook S

NMR in biomedicine

2022 Volume 36, Issue 4, Page(s) e4817

Abstract: Advanced imaging technologies, large-scale metabolomics, and the measurement of gene transcripts or enzyme expression all enable investigations of intermediary metabolism in human patients. Complementary information about fluxes in individual metabolic ... ...

Abstract	Advanced imaging technologies, large-scale metabolomics, and the measurement of gene transcripts or enzyme expression all enable investigations of intermediary metabolism in human patients. Complementary information about fluxes in individual metabolic pathways may be obtained by ex vivo
MeSH term(s)	Humans ; Carbon Isotopes/chemistry ; Magnetic Resonance Spectroscopy/methods ; Magnetic Resonance Imaging ; Metabolomics/methods ; Metabolic Networks and Pathways
Chemical Substances	Carbon Isotopes
Language	English
Publishing date	2022-09-25
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4817
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Article ; Online: Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver.

Jin, Eunsook S / Lee, Min H / Malloy, Craig R

Physiological reports

2020 Volume 8, Issue 16, Page(s) e14554

Abstract: The liver regenerates NADPH via multiple pathways to maintain redox balance and reductive biosynthesis. The pentose phosphate pathway (PPP) contributes to hepatic lipogenesis by supplying NADPH, and it is thought to play a major role in response to ... ...

Abstract	The liver regenerates NADPH via multiple pathways to maintain redox balance and reductive biosynthesis. The pentose phosphate pathway (PPP) contributes to hepatic lipogenesis by supplying NADPH, and it is thought to play a major role in response to oxidative stress. This study determined the significance of the PPP and related NADPH-regenerating enzymes in the liver under oxidative stress. Fasted hamsters received acetaminophen (400 mg/kg) to deplete glutathione in the liver and [U-
MeSH term(s)	Animals ; Cricetinae ; Glutathione/metabolism ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/metabolism ; Liver/metabolism ; Male ; Mesocricetus ; Mitochondria, Liver/metabolism ; Pentose Phosphate Pathway
Chemical Substances	Isocitrate Dehydrogenase (EC 1.1.1.41) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2020-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.14554
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Article ; Online: Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity.

Fordham, Talyia M / Morelli, Nazeen S / Garcia-Reyes, Yesenia / Ware, Meredith A / Rahat, Haseeb / Sundararajan, Divya / Fuller, Kelly N Z / Severn, Cameron / Pyle, Laura / Malloy, Craig R / Jin, Eunsook S / Parks, Elizabeth J / Wolfe, Robert R / Cree, Melanie G

Obesity (Silver Spring, Md.)

2024 Volume 32, Issue 4, Page(s) 678–690

Abstract: Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study' ...

Abstract	Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS. Methods: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 ± 6.5 kg/m Results: Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (-0.8% absolute, -7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (-8%, p = 0.004). Plasma TG (-9%, p = 0.015) and VLDL-TG (-21%, p = 0.031) were reduced as well. VLDL-TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046). Conclusions: Similar to studies in older adults, short-term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.
MeSH term(s)	Adolescent ; Female ; Humans ; Fatty Liver ; Hyperandrogenism/complications ; Insulin ; Insulin Resistance ; Lipoproteins, VLDL ; Obesity/complications ; Polycystic Ovary Syndrome/drug therapy ; Polycystic Ovary Syndrome/complications
Chemical Substances	Insulin ; Lipoproteins, VLDL
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23988
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Zs.A 4061: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

Jin, Eunsook S / Malloy, Craig R / Sharma, Gaurav / Finn, Erin / Fuller, Kelly N Z / Reyes, Yesenia Garcia / Lovell, Mark A / Derderian, Sarkis C / Schoen, Jonathan A / Inge, Thomas H / Cree, Melanie G

Redox biology

2023 Volume 63, Page(s) 102749

Abstract: Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components ... ...

Abstract	Background: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. Methods: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U- Results: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m Conclusions: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.
MeSH term(s)	Humans ; Liver/metabolism ; Glutathione/metabolism ; Glycerol/metabolism ; Male ; Female ; Adolescent ; Young Adult ; Magnetic Resonance Spectroscopy
Chemical Substances	Glutathione (GAN16C9B8O) ; Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2023-05-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2023.102749
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Article ; Online: Fatty liver disrupts glycerol metabolism in gluconeogenic and lipogenic pathways in humans.

Jin, Eunsook S / Browning, Jeffrey D / Murphy, Rebecca E / Malloy, Craig R

Journal of lipid research

2018 Volume 59, Issue 9, Page(s) 1685–1694

Abstract: It is a challenge to assess metabolic dysregulation in fatty liver of human patients prior to clinical manifestations. Here, we recruited obese, but otherwise healthy, subjects to examine biochemical processes in the liver with simple triglyceride ... ...

Abstract	It is a challenge to assess metabolic dysregulation in fatty liver of human patients prior to clinical manifestations. Here, we recruited obese, but otherwise healthy, subjects to examine biochemical processes in the liver with simple triglyceride accumulation using stable isotopes and NMR analysis of metabolic products in blood. Intrahepatic triglycerides were measured using
MeSH term(s)	Adult ; Fatty Liver/metabolism ; Female ; Gluconeogenesis ; Glycerol/metabolism ; Humans ; Lipogenesis ; Male ; Middle Aged ; Young Adult
Chemical Substances	Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2018-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1194/jlr.M086405
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Article ; Online: Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver.

Jin, Eunsook S / Lee, Min Hee / Murphy, Rebecca E / Malloy, Craig R

American journal of physiology. Endocrinology and metabolism

2018 Volume 314, Issue 6, Page(s) E543–E551

Abstract: The pentose phosphate pathway (PPP) is widely assumed to play a key role in both reductive biosynthesis and protection from oxidative stress because it is the major source of NADPH. However, little is known about the activity of the PPP in fatty liver, ... ...

Abstract	The pentose phosphate pathway (PPP) is widely assumed to play a key role in both reductive biosynthesis and protection from oxidative stress because it is the major source of NADPH. However, little is known about the activity of the PPP in fatty liver, which is characterized by both oxidative stress and lipogenesis. This study was designed to test whether the PPP is active in parallel with lipogenesis and antioxidant processes in the fatty liver of whole animals. Eight- and 16-wk-old obese Zucker diabetic fatty rats and their lean littermates received [U-
MeSH term(s)	Animals ; Antioxidants/metabolism ; Catalase/metabolism ; Fatty Liver/complications ; Fatty Liver/metabolism ; Fatty Liver/pathology ; Glutathione/metabolism ; Lipogenesis/physiology ; Liver/metabolism ; Male ; Malondialdehyde/metabolism ; Obesity/complications ; Obesity/metabolism ; Obesity/pathology ; Oxidative Stress/physiology ; Pentose Phosphate Pathway/physiology ; Rats ; Rats, Zucker ; Triglycerides/metabolism
Chemical Substances	Antioxidants ; Triglycerides ; Malondialdehyde (4Y8F71G49Q) ; Catalase (EC 1.11.1.6) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2018-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00342.2017
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Article ; Online: A randomized clinical trial evaluating the effect of empagliflozin on triglycerides in obese adults: Role of visceral fat.

Lee, Min Hee / Neeland, Ian J / de Albuquerque Rocha, Natalia / Hughes, Connor / Malloy, Craig R / Jin, Eunsook S

Metabolism open

2021 Volume 13, Page(s) 100161

Abstract: Background: Empagliflozin, a sodium glucose cotransporter 2 inhibitor, is a medication to treat type 2 diabetes. The effect of empagliflozin in persons without diabetes has received less attention. Here we conducted a randomized, double-blind placebo- ... ...

Abstract	Background: Empagliflozin, a sodium glucose cotransporter 2 inhibitor, is a medication to treat type 2 diabetes. The effect of empagliflozin in persons without diabetes has received less attention. Here we conducted a randomized, double-blind placebo-controlled clinical trial to examine the effect of empagliflozin on plasma triglycerides in obese non-diabetic adults. Methods: Participants (n = 35; BMI ≥ 30 kg/m Results: The changes in blood triglyceride concentration with empagliflozin therapy related to the mass of baseline visceral adipose tissue (VAT; r = 0.53, p = 0.04). Empagliflozin slightly lowered triglycerides in obese subjects with low VAT, but increased triglycerides in the subjects with high VAT. Consistently, empagliflozin effectively suppressed triglyceride synthesis following [U- Conclusions: The effect of empagliflozin on triglycerides in obese adults differed depending on VAT. Empagliflozin suppressed triglyceride synthesis in the subjects with low VAT, but tended to increase triglycerides in those with high VAT.
Language	English
Publishing date	2021-12-25
Publishing country	England
Document type	Journal Article
ISSN	2589-9368
ISSN (online)	2589-9368
DOI	10.1016/j.metop.2021.100161
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