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

Amino acid metabolism in health and disease DOI Creative Commons

Zhenan Ling,

Yifan Jiang,

Jun-Nan Ru

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 13, 2023

Abstract Amino acids are the building blocks of protein synthesis. They structural elements and energy sources cells necessary for normal cell growth, differentiation function. acid metabolism disorders have been linked with a number pathological conditions, including metabolic diseases, cardiovascular immune cancer. In case tumors, alterations in amino can be used not only as clinical indicators cancer progression but also therapeutic strategies. Since growth development tumors depend on intake foreign acids, more studies targeted tumor-related to selectively kill tumor cells. Furthermore, immune-related confirmed that regulates function effector T regulatory cells, affecting Therefore, studying associated disease identifying targets pathways may helpful treatment. This article mainly focuses research tumor-oriented reviews progress diseases related metabolism, order provide theoretical basis therapy metabolism.

Language: Английский

Citations

196
Branched-chain amino acids in cardiovascular disease DOI
Robert W. McGarrah, Phillip J. White

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(2), P. 77 - 89

Published: Sept. 5, 2022

Language: Английский

Citations

144
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus DOI Open Access
Georgia Xourafa,

Melis Korbmacher,

Michael Roden

et al.

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 27 - 49

Published: Oct. 16, 2023

Language: Английский

Citations

92
Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk DOI
Xiangyu Zhang, Divya Kapoor, Se‐Jin Jeong

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(2), P. 359 - 377

Published: Feb. 19, 2024

Language: Английский

Citations

23
SREBP-1c and lipogenesis in the liver: an update DOI
Pascal Ferré, Franck Phan, Fabienne Foufelle

et al.

Biochemical Journal, Journal Year: 2021, Volume and Issue: 478(20), P. 3723 - 3739

Published: Oct. 21, 2021

Sterol Regulatory Element Binding Protein-1c is a transcription factor that controls the synthesis of lipids from glucose in liver, process which utmost importance for storage energy. Discovered early nineties by B. Spiegelman and M. Brown J. Goldstein, it has generated more than 5000 studies order to elucidate its mechanism activation role physiology pathology. Synthetized as precursor found membranes endoplasmic reticulum, be exported Golgi cleaved called regulated intramembrane proteolysis. We reviewed 2002 main characteristics, regulation hepatic glycolytic lipogenic genes. particularly emphasized mediator insulin effects on these In present review, we would like update informations focus response another actor activation, reticulum stress.

Language: Английский

Citations

92
Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation DOI Creative Commons
Sophie Trefely, Katharina Huber, Joyce Liu

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 82(2), P. 447 - 462.e6

Published: Dec. 1, 2021

Language: Английский

Citations

73
Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis DOI Creative Commons
Federica Barutta, Stefania Bellini, Marilena Durazzo

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(1), P. 178 - 178

Published: Jan. 16, 2022

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported underestimated. Both epidemiological intervention studies show a bidirectional relationship between periodontitis diabetes. The hypothesis of potential causal link the diseases is corroborated by recent in experimental animals that identified mechanisms whereby can adversely affect each other. Herein, we will review clinical data on existence two-way discuss possible mechanistic interactions both directions, focusing particular new highlighting importance host response. Moreover, address trained immunity may represent unifying mechanism explaining intertwined association periodontitis. Achieving better insight clustering infectious, inflammatory, metabolic provide therapeutic options to reduce risk diabetes-associated comorbidities.

Language: Английский

Citations

59
Role of Branched-Chain Amino Acid Metabolism in Type 2 Diabetes, Obesity, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease DOI Open Access
Paola Cuomo,

Rosanna Capparelli,

Antonio Iannelli

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4325 - 4325

Published: April 13, 2022

Branched-chain amino acids (BCAAs) include leucine, isoleucine, and valine. Mammalians cannot synthesize these de novo must acquire them through their diet. High levels of BCAAs are associated with insulin resistance; type 2 diabetes; obesity; non-metabolic diseases, including several forms cancer. BCAAs—in particular leucine—activate the rapamycin complex1 mTORC1, which regulates cell growth metabolism, glucose metabolism more essential physiological processes. Diets rich in metabolic diseases (listed above), while diets low generally reported to promote health. As for dysregulation caused by high BCAAs, recent studies propose that accumulation acyl-carnitine diacyl-CoA muscles alters lipid metabolism. However, this suggestion is not broadly accepted. On clinical grounds, pre- post-operative profiles candidate patients bariatric surgery being used select optimal procedure each individual patient.

Language: Английский

Citations

56
Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue DOI Creative Commons
Ricardo J. Samms, Guo‐Fang Zhang, Wentao He

et al.

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 64, P. 101550 - 101550

Published: July 31, 2022

Tirzepatide, a dual GIP and GLP-1 receptor agonist, delivered superior glycemic control weight loss compared to selective (GLP-1R) agonism in patients with type 2 diabetes (T2D). These results have fueled mechanistic studies focused on understanding how tirzepatide achieves its therapeutic efficacy. Recently, we found that treatment improves insulin sensitivity humans T2D obese mice concert reduction circulating levels of branched-chain amino (BCAAs) keto (BCKAs) acids, metabolites associated development systemic resistance (IR) T2D. Importantly, these effects were be coupled increased expression BCAA catabolic genes thermogenic brown adipose tissue (BAT) mice. findings led us hypothesize may lower BCAAs/BCKAs by promoting their catabolism BAT. To address this question, utilized murine model diet-induced obesity employed stable-isotope tracer combination metabolomic analyses BAT other tissues. Treatment stimulated BAT, as demonstrated labeling BCKA-derived metabolites, increases byproducts breakdown, including glutamate, alanine, 3-hydroxyisobutyric acid (3-HIB). Further, chronic administration multiple acids previously been shown elevated response cold exposure. Finally, substantial increase several TCA cycle intermediates (α-ketoglutarate, fumarate, malate) suggest induces thermogenic-like profile an effect account for reduced BCAAs IR

Language: Английский

Citations

48
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