Branched‐chain amino acids and type 2 diabetes: a bidirectional Mendelian randomization analysis DOI Open Access
Jonathan D. Mosley, Mingjian Shi,

David Agamasu

et al.

Obesity, Journal Year: 2024, Volume and Issue: 32(2), P. 423 - 435

Published: Jan. 25, 2024

Abstract Objective Genetic studies have suggested that the branched‐chain amino acids (BCAAs) valine, leucine, and isoleucine a causal association with type 2 diabetes (T2D). However, inferences are based on limited number of genetic loci associated BCAAs. Methods Instrumental variables (IVs) for each BCAA were constructed validated using large well‐powered data sets their T2D was tested two‐sample inverse‐variance weighted Mendelian randomization approach. Sensitivity analyses performed to ensure accuracy findings. A reverse assessed instrumental T2D. Results Estimated effect sizes between IVs T2D, excluding outliers, as follows: valine (β = 0.14 change in log‐odds per SD 95% CI: −0.06 0.33, p 0.17), leucine 0.15, −0.02 0.32, 0.09), 0.13, −0.08 0.34, 0.24). In contrast, positively BCAA, i.e., 0.08 levels 0.05 0.10, 1.8 × 10 −9 ), 0.06, 0.04 0.09, 4.5 −8 0.08, 2.8 ). Conclusions These suggest BCAAs not mediators risk but biomarkers diabetes.

Language: Английский

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders DOI Creative Commons
Chuang Du, Wenjie Liu, Jing Yang

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: July 18, 2022

Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential in human physiology. Decades studies have revealed their roles protein synthesis, regulating neurotransmitter the mechanistic target rapamycin (mTOR). BCAAs found to be related many metabolic disorders, such as insulin resistance, obesity, heart failure. Also, diseases alteration BCAA catabolism enzyme branched-chain α-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, autism with epilepsy, so on. In this review, corresponding therapies discussed after introduction detection methods BCKDK. interaction between microbiota is highlighted.

Language: Английский

Citations

43
The role of mitochondria in myocardial damage caused by energy metabolism disorders: From mechanisms to therapeutics DOI
Aolin Li, Lu Lian,

Xin-nong Chen

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 236 - 251

Published: Aug. 9, 2023

Language: Английский

Citations

35
PPM1K-regulated impaired catabolism of branched-chain amino acids orchestrates polycystic ovary syndrome DOI Creative Commons
Liangshan Mu,

Zhenhong Ye,

Junhao Hu

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 89, P. 104492 - 104492

Published: March 1, 2023

Language: Английский

Citations

28
Branched-chain amino acid catabolism in muscle affects systemic BCAA levels but not insulin resistance DOI

Megan C. Blair,

Michael D. Neinast, Cholsoon Jang

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(4), P. 589 - 606

Published: April 26, 2023

Language: Английский

Citations

26
The central role of the gut microbiota in the pathophysiology and management of type 2 diabetes DOI

Daniel P Baars,

Marcos F. Fondevila, Abraham S. Meijnikman

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(8), P. 1280 - 1300

Published: Aug. 1, 2024

Language: Английский

Citations

15
Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health DOI Creative Commons
Simon Lecoutre, Salwan Maqdasy, David Rizo‐Roca

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: July 15, 2024

Glutamine and glutamate are interconverted by several enzymes alterations in this metabolic cycle linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized decreased plasma white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes perturbed fat cell glutaminase glutamine synthase messenger RNA protein abundance, which together promote glutaminolysis. In human adipocytes, reductions activity aerobic glycolysis mitochondrial oxidative capacity via increases hypoxia-inducible factor 1α lactate levels p38 mitogen-activated kinase signalling. Systemic inhibition male female mice, or genetically adipocytes of triggers the activation thermogenic gene programs inguinal adipocytes. Consequently, knockout mice display higher energy expenditure improved glucose tolerance compared control littermates, even under high-fat diet conditions. Altogether, our findings highlight adipocyte turnover as an important determinant health.

Language: Английский

Citations

10
Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease DOI Open Access
Sumit Kumar Anand, Theresea-Anne Governale, Xiangyu Zhang

et al.

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: 194(4), P. 510 - 524

Published: Jan. 1, 2024

Language: Английский

Citations

9
A pilot study on screening for aminoacidurias using paper chromatography in subjects with type 2 diabetes and healthy subjects: Cross-sectional study DOI

Sushma BJ,

Vaibhav Gupta

International Journal of Clinical Biochemistry and Research, Journal Year: 2025, Volume and Issue: 11(4), P. 260 - 268

Published: Jan. 11, 2025

Diabetes is a heterogeneous chronic dysglycemic and dyslipidemic metabolic disorder principally characterized by persistent hyperglycemia resulting from defects in insulin action and/or secretion. This pilot study indented detect type of Aminoacidurias number amino acids detected the urine correlate with glycemic control marker glycated hemoglobin (HbA1c) 2 diabetic subjects healthy controls. present included 40 diabetes age gender matched controls group 25-60 years. Early morning first voided mid-stream sample 5 mL was collected into container subjected to centrifugation remove cell debris clear supernatant used for preforming paper chromatography detecting aminoacidurias. In two or more than up seven are comparison The most commonly were valine (60%), glycine (45%), leucine (32.5%), alanine (22.5%) histidine (25%). There statistically significant strong correlation existed between HbA1c levels (r=0.901). We found significantly elevated fasting plasma glucose compared excreted It observed that those patients inadequate had evidenced strongly values. Detection can be as non-invasive tool predict patients. addition this, we get an information about deficient increased which open gateway therapeutic modalities using acids.

Language: Английский

Citations

1
Dogs fed a high protein, low carbohydrate diet have elevated postprandial plasma glucagon and amino acid concentrations and tend to have lower glucose concentrations compared to two different moderate protein, moderate carbohydrate diets DOI Creative Commons
Sydney Banton,

Shari Raheb,

Pawanpreet Singh

et al.

Translational Animal Science, Journal Year: 2025, Volume and Issue: 9

Published: Jan. 1, 2025

As dog owners continue to seek feed their dogs similarly themselves, there is demand for high protein, low carbohydrate (HPLC) diets. The consumption of HPLC diets can improve glycemic control, fiber However, the effects and on cardiac function have yet be evaluated in healthy dogs. objective present study was investigate glucose, insulin, glucagon amino acid (AA) postprandial response echocardiographic measurements laboratory-housed, adult large breed fed a commercially available HPLC, moderate (MPMC), or MPMC, fiber, "metabolic" diet 42 d. This conducted as 3 × Latin square where received: 1) commercial (48% metabolizable energy (ME) from 10% ME nitrogen-free extract; NFE), 2) MPMC (28% 39% NFE) formulated with same ingredients 3) (MET) (30% 37% control. An echocardiogram 12-h insulin 6-h AA meal were performed day feeding. Data analyzed using proc glimmix SAS (version 9.4). All parameters remained within reference range this size. Dogs had larger net area under curve (NetAUC) plasma (P < 0.001) compared MET, smaller NetAUC glucose: = 0.039) but MET similar both. Glucose tended different among treatments 0.057), greater netAUC than HPLC. concentrations Ile, Leu, Lys, Thr, Tyr Val over time Gln Met 0.05). may improved glucose uptake diet. research provides first insight into cardiometabolic health consuming three differing content.

Language: Английский

Citations

1
Amino Acid Homeostasis in Mammalian Cells with a Focus on Amino Acid Transport DOI Creative Commons
Stefan Bröer, Gregory Gauthier-Coles

Journal of Nutrition, Journal Year: 2021, Volume and Issue: 152(1), P. 16 - 28

Published: Sept. 18, 2021

Amino acid homeostasis is maintained by import, export, oxidation, and synthesis of nonessential amino acids, the breakdown protein. These processes work in conjunction with regulatory elements that sense acids or their metabolites. During after nutrient intake, dominated autoregulatory such as transport oxidation excess acids. deprivation triggers autophagy execution broader transcriptional programs to maintain plasma concentrations. plays a crucial role absorption intestine, distribution across cells organs, recycling kidney, protein breakdown.

Language: Английский

Citations

49