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Article ; Online: Type 2 diabetes and succinate: unmasking an age-old molecule.

Fernández-Veledo, Sonia / Marsal-Beltran, Anna / Vendrell, Joan

2024 Volume 67, Issue 3, Page(s) 430–442

Abstract: Beyond their conventional roles in intracellular energy production, some traditional metabolites also function as extracellular messengers that activate cell-surface G-protein-coupled receptors (GPCRs) akin to hormones and neurotransmitters. These ... ...

Abstract	Beyond their conventional roles in intracellular energy production, some traditional metabolites also function as extracellular messengers that activate cell-surface G-protein-coupled receptors (GPCRs) akin to hormones and neurotransmitters. These signalling metabolites, often derived from nutrients, the gut microbiota or the host's intermediary metabolism, are now acknowledged as key regulators of various metabolic and immune responses. This review delves into the multi-dimensional aspects of succinate, a dual metabolite with roots in both the mitochondria and microbiome. It also connects the dots between succinate's role in the Krebs cycle, mitochondrial respiration, and its double-edge function as a signalling transmitter within and outside the cell. We aim to provide an overview of the role of the succinate-succinate receptor 1 (SUCNR1) axis in diabetes, discussing the potential use of succinate as a biomarker and the novel prospect of targeting SUCNR1 to manage complications associated with diabetes. We further propose strategies to manipulate the succinate-SUCNR1 axis for better diabetes management; this includes pharmacological modulation of SUCNR1 and innovative approaches to manage succinate concentrations, such as succinate administration and indirect strategies, like microbiota modulation. The dual nature of succinate, both in terms of origins and roles, offers a rich landscape for understanding the intricate connections within metabolic diseases, like diabetes, and indicates promising pathways for developing new therapeutic strategies.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2 ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Succinates/metabolism
Chemical Substances	Receptors, G-Protein-Coupled ; Succinates
Language	English
Publishing date	2024-01-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-023-06063-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 279: Show issues

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Article ; Online: Rethinking succinate: an unexpected hormone-like metabolite in energy homeostasis.

Fernández-Veledo, Sonia / Ceperuelo-Mallafré, Victòria / Vendrell, Joan

Trends in endocrinology and metabolism: TEM

2021 Volume 32, Issue 9, Page(s) 680–692

Abstract: There has been an explosion of interest in the signaling capacity of energy metabolites. A prime example is the Krebs cycle substrate succinate, an archetypal respiratory substrate with functions beyond energy production as an intracellular and ... ...

Abstract	There has been an explosion of interest in the signaling capacity of energy metabolites. A prime example is the Krebs cycle substrate succinate, an archetypal respiratory substrate with functions beyond energy production as an intracellular and extracellular signaling molecule. Long associated with inflammation, emerging evidence supports a key role for succinate in metabolic processes relating to energy management. As the natural ligand for SUCNR1, a G protein-coupled receptor, succinate is akin to hormones and likely functions as a reporter of metabolism and stress. In this review, we reconcile new and old observations to outline a regulatory role for succinate in metabolic homeostasis. We highlight the importance of the succinate-SUCNR1 axis in metabolic diseases as an integrator of macrophage immune response, and we discuss new metabolic functions recently ascribed to succinate in specific tissues. Because circulating succinate has emerged as a promising biomarker in chronic metabolic diseases, a better understanding of the physiopathological role of the succinate-SUCNR1 axis in metabolism might open new avenues for clinical use in patients with obesity or diabetes.
MeSH term(s)	Animals ; Energy Metabolism ; Homeostasis ; Humans ; Receptors, G-Protein-Coupled ; Succinic Acid
Chemical Substances	Receptors, G-Protein-Coupled ; Succinic Acid (AB6MNQ6J6L)
Language	English
Publishing date	2021-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2021.06.003
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Zs.A 2999: Show issues

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Article ; Online: Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Fernández-Veledo, Sonia / Vendrell, Joan

Reviews in endocrine & metabolic disorders

2019 Volume 20, Issue 4, Page(s) 439–447

Abstract: There is now a wealth of evidence showing that communication between microbiota and the host is critical to sustain the vital functions of the healthy host, and disruptions of this homeostatic coexistence are known to be associated with a range of ... ...

Abstract	There is now a wealth of evidence showing that communication between microbiota and the host is critical to sustain the vital functions of the healthy host, and disruptions of this homeostatic coexistence are known to be associated with a range of diseases including obesity and type 2 diabetes. Microbiota-derived metabolites act both as nutrients and as messenger molecules and can signal to distant organs in the body to shape host pathophysiology. In this review, we provide a new perspective on succinate as a gut microbiota-derived metabolite with a key role governing intestinal homeostasis and energy metabolism. Thus, succinate is not merely a major intermediary of the TCA traditionally considered as an extracellular danger signal in the host, but also a by-product of some bacteria and a primary cross-feeding metabolite between gut resident microbes. In addition to maintain a healthy microbiome, specific functions of microbiota-derived succinate in peripheral tissues regulating host nutrient metabolism should not be rule out. Indeed, recent research point to some probiotic interventions directed to modulate succinate levels in the intestinal lumen, as a new microbiota-based therapies to treat obesity and related co-morbidities. While further research is essential, a large body of evidence point to succinate as a new strategic mediator in the microbiota-host cross-talk, which might provide the basis for new therapeutically approaches in a near future.
MeSH term(s)	Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Metabolic Diseases/microbiology ; Succinic Acid/metabolism
Chemical Substances	Succinic Acid (AB6MNQ6J6L)
Language	English
Publishing date	2019-10-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2185718-0
ISSN	1573-2606 ; 1389-9155
ISSN (online)	1573-2606
ISSN	1389-9155
DOI	10.1007/s11154-019-09513-z
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Zs.A 6069: Show issues

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Article: Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles.

Insenser, María / Vilarrasa, Nuria / Vendrell, Joan / Escobar-Morreale, Héctor F

Journal of clinical medicine

2021 Volume 10, Issue 17

Abstract: Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women ... ...

Abstract	Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D. After surgery, diabetes remitted in 7 of the 11 patients with T2D. Plasma protein profiles at baseline and 6 months after bariatric surgery were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight coupled to mass spectrometry (MALDI-TOF/TOF MS). Remission of T2D following bariatric procedures was associated with changes in alpha-1-antichymotrypsin (SERPINA 3,
Language	English
Publishing date	2021-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10173879
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Article: New Insights in Cytokines in Childhood Obesity: Changes in TWEAK and CD163 After a 2-Year Intervention Program in Prepubertal Children With Obesity.

Escartín, Rocío / Font, Maria / González-Clemente, José Miguel / Vendrell, Joan / Caixàs, Assumpta / Corripio, Raquel

Frontiers in endocrinology

2022 Volume 13, Page(s) 909201

Abstract: Objective: Obesity is characterized by a low-grade inflammatory state in adipose tissue. Tumor Necrosis Factor Weak Inducer of Apoptosis (TWEAK) and Cluster of Differentiation 163 (CD163) are cytokines potentially involved in the pathogenesis of obesity. ...

Abstract	Objective: Obesity is characterized by a low-grade inflammatory state in adipose tissue. Tumor Necrosis Factor Weak Inducer of Apoptosis (TWEAK) and Cluster of Differentiation 163 (CD163) are cytokines potentially involved in the pathogenesis of obesity. Little is known about them in children. The aim of this study was to observe serum levels of TWEAK and CD163 in prepubertal children with obesity compared to lean, and to evaluate its changes after a 2-year intervention program in children with obesity. Methods: Case-control study with a prospective follow-up of cases for 2 years in a referral pediatric endocrine outpatient centre. Seventy-three prepubertal children with obesity, and forty-seven age- and gender-matched lean controls were studied. Sixty-two cases finished the program. Anthropometric parameters, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipid profile, and concentrations of TWEAK and CD163 were determined. Children with obesity were re-evaluated after a 2-year intervention program consisting of diet and exercise. Weight loss was considered if z-score Body Mass Index (BMI) decreased at least 0.5 Standard Deviations (SD). Results: We observed higher CD163 levels in children with obesity compared to controls. No significant differences were observed in TWEAK and CD163/TWEAK ratio at baseline. After the 2-year intervention program, TWEAK levels were higher and CD163/TWEAK ratio was lower in children with weight loss than those without weight loss. CD163 decreased in both groups. Conclusion: TWEAK and CD163 seem to have a role in the pathogenesis of obesity in prepubertal children.
MeSH term(s)	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Case-Control Studies ; Child ; Cytokine TWEAK/metabolism ; Cytokines ; Humans ; Pediatric Obesity/therapy ; Prospective Studies ; Receptors, Cell Surface ; Weight Loss
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD163 antigen ; Cytokine TWEAK ; Cytokines ; Receptors, Cell Surface ; TNFSF12 protein, human
Language	English
Publishing date	2022-07-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.909201
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Protocol for the in vitro isolation and culture of mature adipocytes and white adipose tissue explants from humans and mice.

Villanueva-Carmona, Teresa / Cedó, Lídia / Núñez-Roa, Catalina / Maymó-Masip, Elsa / Vendrell, Joan / Fernández-Veledo, Sonia

STAR protocols

2023 Volume 4, Issue 4, Page(s) 102693

Abstract: White adipose tissue (WAT) explants culture allows the study of this tissue ex vivo, maintaining its structure and properties. Concurrently, isolating mature adipocytes facilitates research into fat cell metabolism and hormonal regulation. Here, we ... ...

Abstract	White adipose tissue (WAT) explants culture allows the study of this tissue ex vivo, maintaining its structure and properties. Concurrently, isolating mature adipocytes facilitates research into fat cell metabolism and hormonal regulation. Here, we present a protocol for obtaining, isolating, and processing mature adipocytes, alongside the cultivation of WAT explants from humans and mice. We describe steps for WAT retrieval, culturing of WAT explants, WAT digestion, and adipocytes separation. We then detail procedures for culturing isolated mature adipocytes. For complete details on the use and execution of this protocol, please refer to Villanueva-Carmona et al. (2023).
MeSH term(s)	Humans ; Mice ; Animals ; Adipose Tissue, White ; Adipocytes
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102693
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Article ; Online: Comment on Serés-Noriega et al. Use of the Steno T1 Risk Engine Identifies Preclinical Atherosclerosis Better Than Use of ESC/EASD-2019 in Adult Subjects With Type 1 Diabetes at High Risk. Diabetes Care 2022;45:2412-2421.

González-Clemente, José-Miguel / Llauradó, Gemma / Cano, Albert / Giménez-Palop, Olga / Albert, Lara / Vendrell, Joan

Diabetes care

2023 Volume 46, Issue 3, Page(s) e85–e86

MeSH term(s)	Humans ; Adult ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Atherosclerosis
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc22-2344
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 365: Show issues

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Article ; Conference proceedings ; Online: Pipe Life Prognosis in Water Distribution Networks using Reliable Data-based Approaches

Henry, David / Sun, Congcong / Vendrell, Joan / Puig, Vicenç / Bonet, Enric

5th Conference on Control and Fault-Tolerant Systems, SysTol 2021 ; ISBN: 9781665431590

2021

Abstract: The assessment and prognosis of pipe life in water distribution networks has great potential in optimizing asset investment and protecting water resources. In the state-of-the-art, most of the research work about pipe life assessment focuses on revealing ...

Abstract	The assessment and prognosis of pipe life in water distribution networks has great potential in optimizing asset investment and protecting water resources. In the state-of-the-art, most of the research work about pipe life assessment focuses on revealing associated variables and regulations for the occurrence of pipe failures, which has scientific value but still far from assisting water industry directly in real operation. In order to provide a pipe life assessment and prognosis approach with practical significance, this paper presents: 1) a comparable approach to quantify impact of different factors (mainly age, material and diameter) on the occurrence of pipe failures using statistical reliability model based on cumulative Weibull distribution, survival model based on neural networks and evolutionary polynomial regression model for pipe deterioration; 2) a prognosis method for the remaining useful life of pipes using previous algorithms; 3) a maintenance and renewal plan of the network to assist daily operation of water operators by means of a checklist including risk levels (low, medium, high) under different factor ranges. The Barcelona water distribution network is used as a real life case study, demonstrating how the proposed approaches can be used.
Keywords	Life Science
Language	English
Publisher	IEEE
Publishing country	nl
Document type	Article ; Conference proceedings ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comment on Fahrmann et al. Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 2021;44;2132-2139.

González-Clemente, José-Miguel / Llauradó, Gemma / Romero, Ana / Giménez-Palop, Olga / Berlanga, Eugenio / Vendrell, Joan

Diabetes care

2022 Volume 45, Issue 3, Page(s) e63–e64

MeSH term(s)	Diabetes Mellitus, Type 1/drug therapy ; Follow-Up Studies ; Humans ; Hypoglycemia ; Myocardial Ischemia
Language	English
Publishing date	2022-03-04
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc21-2262
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances.

Ballesteros, Mónica / Gil-Lluís, Pilar / Ejarque, Miriam / Diaz-Perdigones, Cristina / Martinez-Guasch, Laia / Fernández-Veledo, Sonia / Vendrell, Joan / Megía, Ana

The Journal of clinical endocrinology and metabolism

2022 Volume 107, Issue 10, Page(s) 2748–2757

Abstract: Context: DNA methylation in the diagnosis of gestational diabetes.: Objective: To assess the value of DNA methylation in the diagnosis of gestational diabetes (GDM) and in the prediction of maternal postpartum glucose disturbances.: Methods: Two- ... ...

Abstract	Context: DNA methylation in the diagnosis of gestational diabetes. Objective: To assess the value of DNA methylation in the diagnosis of gestational diabetes (GDM) and in the prediction of maternal postpartum glucose disturbances. Methods: Two-stage observational study performed between July 2006 and December 2010, at University Hospital. Forty-eight randomly selected pregnant women formed the discovery cohort (24 with GDM and 24 controls) and 252 pregnant women (94 with GDM and 158 controls) formed the replication cohort. GDM women were re-evaluated 4 years postpartum. The main outcome measures were GDM, type 2 diabetes or prediabetes at 4 years postpartum. Results: We identified 3 CpG sites related to LINC00917, TRAPPC9, and LEF1 that were differentially methylated in women with GDM and abnormal glucose tolerance; and sites associated with LINC00917 and TRAPPC9 were independently associated with an abnormal glucose tolerance status 4 years postpartum after controlling for clinical variables. Moreover, the site associated with LINC00917 and the combination of the 3 sites had the highest predictive values. Conclusion: Our results suggest that some of these sites may be implicated in the development of GDM and postpartum abnormal glucose tolerance.
MeSH term(s)	Blood Glucose ; DNA Methylation ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/genetics ; Diabetes, Gestational/diagnosis ; Diabetes, Gestational/genetics ; Female ; Glucose ; Glucose Intolerance/diagnosis ; Glucose Intolerance/genetics ; Glucose Tolerance Test ; Humans ; Postpartum Period ; Pregnancy
Chemical Substances	Blood Glucose ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgac462
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