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2. Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD

Author

Marsal-Beltran, Anna, Rodríguez-Castellano, Adrià, Astiarraga, Brenno, Calvo, Enrique, Rada, Patricia, Madeira, Ana, Rodríguez-Peña, M-Mar, Llauradó, Gemma, Núñez-Roa, Catalina, Gómez-Santos, Beatriz, Maymó-Masip, Elsa, Bosch, Ramon, Frutos, María Dolores, Moreno-Navarrete, José María, Ramos-Molina, Bruno, Aspichueta, Patricia, Joven, Jorge, Fernández-Real, José-Manuel, Quer, Juan Carlos, Valverde, Ángela M., Pardo, Albert, Vendrell, Joan, Ceperuelo-Mallafré, Victòria, and Fernández-Veledo, Sonia

Published
2023
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6. Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation

Author

Latorre, Jessica, Díaz-Trelles, Ramon, Comas, Ferran, Gavaldà-Navarro, Aleix, Milbank, Edward, Dragano, Nathalia, Morón-Ros, Samantha, Mukthavaram, Rajesh, Ortega, Francisco, Castells-Nobau, Anna, Oliveras-Cañellas, Núria, Ricart, Wifredo, Karmali, Priya P., Tachikawa, Kiyoshi, Chivukula, Pad, Villarroya, Francesc, López, Miguel, Giralt, Marta, Fernández-Real, José Manuel, and Moreno-Navarrete, José María

Published
2022
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7. Downregulation of peripheral lipopolysaccharide binding protein impacts on perigonadal adipose tissue only in female mice

Author

Comas, Ferran, Díaz-Trelles, Ramon, Gavaldà-Navarro, Aleix, Milbank, Edward, Dragano, Nathalia, Morón-Ros, Samantha, Mukthavaram, Rajesh, Latorre, Jessica, Ortega, Francisco, Arnoriaga-Rodriguez, Maria, Oliveras-Cañellas, Núria, Ricart, Wifredo, Karmali, Priya P., Tachikawa, Kiyoshi, Chivukula, Pad, Villarroya, Francesc, Giralt, Marta, López, Miguel, Fernández-Real, José Manuel, and Moreno-Navarrete, José María

Published
2022
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8. Microbiota alterations in proline metabolism impact depression

Author

Mayneris-Perxachs, Jordi, Castells-Nobau, Anna, Arnoriaga-Rodríguez, María, Martin, Miquel, de la Vega-Correa, Lisset, Zapata, Cristina, Burokas, Aurelijus, Blasco, Gerard, Coll, Clàudia, Escrichs, Anira, Biarnés, Carles, Moreno-Navarrete, José María, Puig, Josep, Garre-Olmo, Josep, Ramos, Rafel, Pedraza, Salvador, Brugada, Ramón, Vilanova, Joan Carles, Serena, Joaquín, Gich, Jordi, Ramió-Torrentà, Lluís, Pérez-Brocal, Vicente, Moya, Andrés, Pamplona, Reinald, Sol, Joaquim, Jové, Mariona, Ricart, Wifredo, Portero-Otin, Manuel, Deco, Gustavo, Maldonado, Rafael, and Fernández-Real, José Manuel

Published
2022
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9. ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids

Author

Menghini, Rossella, Hoyles, Lesley, Cardellini, Marina, Casagrande, Viviana, Marino, Arianna, Gentileschi, Paolo, Davato, Francesca, Mavilio, Maria, Arisi, Ivan, Mauriello, Alessandro, Montanaro, Manuela, Scimeca, Manuel, Barton, Richard H., Rappa, Francesca, Cappello, Francesco, Vinciguerra, Manlio, Moreno-Navarrete, José Maria, Ricart, Wifredo, Porzio, Ottavia, Fernández-Real, José-Manuel, Burcelin, Rémy, Dumas, Marc-Emmanuel, and Federici, Massimo

Published
2022
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10. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans

Author

Mayneris-Perxachs, Jordi, Castells-Nobau, Anna, Arnoriaga-Rodríguez, María, Garre-Olmo, Josep, Puig, Josep, Ramos, Rafael, Martínez-Hernández, Francisco, Burokas, Aurelijus, Coll, Clàudia, Moreno-Navarrete, José Maria, Zapata-Tona, Cristina, Pedraza, Salvador, Pérez-Brocal, Vicente, Ramió-Torrentà, Lluís, Ricart, Wifredo, Moya, Andrés, Martínez-García, Manuel, Maldonado, Rafael, and Fernández-Real, José-Manuel

Published
2022
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16. The Microbiota and Energy Balance

Author

Xifra, Gemma, Moreno-Navarrete, José Maria, Fernández-Real, José Manuel, Lenzi, Andrea, Series Editor, Jannini, Emmanuele A., Series Editor, Sbraccia, Paolo, editor, and Finer, Nicholas, editor

Published
2019
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20. Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition

Author

Palomo-Buitrago, María Encarnación, Sabater-Masdeu, Mònica, Moreno-Navarrete, Jose Maria, Caballano-Infantes, Estefanía, Arnoriaga-Rodríguez, María, Coll, Clàudia, Ramió, Lluís, Palomino-Schätzlein, Martina, Gutiérrez-Carcedo, Patricia, Pérez-Brocal, Vicente, Simó, Rafael, Moya, Andrés, Ricart, Wifredo, Herance, José Raúl, and Fernández-Real, José Manuel

Published
2019
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24. Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health

Author

Laurans, Ludivine, Venteclef, Nicolas, Haddad, Yacine, Chajadine, Mouna, Alzaid, Fawaz, Metghalchi, Sarvenaz, Sovran, Bruno, Denis, Raphael G. P., Dairou, Julien, Cardellini, Marina, Moreno-Navarrete, Jose-Maria, Straub, Marjolene, Jegou, Sarah, McQuitty, Claire, Viel, Thomas, Esposito, Bruno, Tavitian, Bertrand, Callebert, Jacques, Luquet, Serge H., Federici, Massimo, Fernandez-Real, José Manuel, Burcelin, Remy, Launay, Jean-Marie, Tedgui, Alain, Mallat, Ziad, Sokol, Harry, and Taleb, Soraya

Published
2018
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30. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness

Author

Morton, Nicholas M., Beltram, Jasmina, Carter, Roderick N., Michailidou, Zoi, Gorjanc, Gregor, McFadden, Clare, Barrios- Llerena, Martin E., Rodriguez-Cuenca, Sergio, Gibbins, Matthew T.G., Aird, Rhona E., Moreno-Navarrete, Jose Maria, Munger, Steven C., Svenson, Karen L., Gastaldello, Annalisa, Ramage, Lynne, Naredo, Gregorio, Zeyda, Maximilian, Wang, Zhao V., Howie, Alexander F., Saari, Aila, Sipila, Petra, Stulnig, Thomas M., Gudnason, Vilmundur, Kenyon, Christopher J., Seckl, Jonathan R., Walker, Brian R., Webster, Scott P., Dunbar, Donald R., Churchill, Gary A., Vidal-Puig, Antonio, Fernandez-Real, Jose Manuel, Emilsson, Valur, and Horvat, Simon

Subjects
Obesity -- Genetic aspects -- Development and progression, Gene expression -- Health aspects, Transferases -- Identification and classification, Biological sciences, Health
Abstract

The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes., Obesity prevalence seems to have plateaued at ~40% (refs. 1,2), suggesting that environmental penetrance (such as a hypercaloric diet or a sedentary lifestyle) is limited to a subpopulation of individuals [...]

Published
2016
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37. Insulin resistance modulates iron-related proteins in adipose tissue

Author

Moreno-Navarrete, Jose Maria, Novelle, Marta G., Catalan, Victoria, Ortega, Francisco, Moreno, Maria, Gomez-Ambrosi, Javier, Xifra, Gemma, Serrano, Marta, Guerra, Ester, Fruhbeck, Wifredo RicarGema, Dieguez, Carlos, and Fernandez-Real, Jose Manuel

Subjects
Adipose tissues -- Research -- Analysis, Iron proteins -- Research -- Analysis, Insulin resistance -- Research -- Analysis -- Physiological aspects, Health
Abstract

OBJECTIVE Circulating markers of iron overload are associated with insulin resistance. Less is known about the impact of iron overload on adipose tissue (AT). We hypothesized that gene expression markers [...]

Published
2014
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38. Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids

Author

Arnoriaga-Rodríguez, María, Mayneris-Perxachs, Jordi, Burokas, Aurelijus, Contreras-Rodríguez, Oren, Blasco, Gerard, Coll, Clàudia, Biarnés, Carles, Miranda-Olivos, Romina, Latorre, Jèssica, Moreno-Navarrete, José-Maria, Castells-Nobau, Anna, Sabater, Mònica, Palomo-Buitrago, María Encarnación, Puig, Josep, Pedraza, Salvador, Gich, Jordi, Pérez-Brocal, Vicente, Ricart, Wifredo, Moya, Andrés, Fernández-Real, Xavier, Ramió-Torrentà, Lluís, Pamplona, Reinald, Sol, Joaquim, Jové, Mariona, Portero-Otin, Manuel, Maldonado, Rafael, and Fernández-Real, José Manuel

Published
2020
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39. Decreased RB1 mRNA, protein, and activity reflect obesity-induced altered adipogenic capacity in human adipose tissue

Author

Moreno-Navarrete, Jose Maria, Petrov, Petar, Serrano, Marta, Ortega, Francisco, Garcia-Ruiz, Estefania, Oliver, Paula, Ribot, Joan, Ricart, Wifredo, Palou, Andreu, Bonet, Ma Luisa, and Fernandez-Real, Jose Manuel

Subjects
Gene expression -- Research -- Analysis, Adipose tissues -- Research -- Analysis -- Physiological aspects, Health
Abstract

Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPARγ and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes., Adipose tissue plays a central role in the management of systemic energy storage as well as in many other processes. This is due to its capacity to store triglycerides and [...]

Published
2013
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40. The L-α-lysophosphatidylinositol/GPR55 system and its potential role in human obesity

Author

Moreno-Navarrete, Jose Maria, Catalan, Victoria, Whyte, Lauren, Diaz-Arteaga, Adenis, Vazquez-Martinez, Rafael, Rotellar, Fernando, Guzman, Rocio, Gomez-Ambrosi, Javier, Pulido, Marina R., Russell, Wendy R., Imbernon, Monica, Ross, Ruth A., Malagon, Maria M., Dieguez, Carlos, Fernandez-Real, Jose Manuel, Fruhbeck, Gema, and Nogueiras, Ruben

Subjects
Obesity -- Research -- Genetic aspects, Cell receptors -- Research -- Genetic aspects, Health
Abstract

GPR55 is a putative cannabinoid receptor, and L-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenlc genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. Diabetes 61:281-291, 2012, In addition to their ability to store triacylglycerol, adipocytes act as endocrine secretory cells (1). A growing number of adipocyte-derived factors have been described, and their contribution to the pathophysiology [...]

Published
2012
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41. Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance

Author

Pellegrinelli, Vanessa, primary, Rodriguez-Cuenca, Segio, additional, Rouault, Christine, additional, Schilbert, Hanna, additional, Virtue, Sam, additional, Moreno-Navarrete, Jose Maria, additional, Bidault, Guillaume, additional, Borrego, Maria del Carmen Vázquez, additional, Dias, Ana Rita, additional, Pucker, Boas, additional, Dale, Martin, additional, Campbell, Mark, additional, Carobbio, Stefania, additional, Aron-Wisnewsky, Judith, additional, Mora, Silvia, additional, Masiero, Mauro, additional, Emmanouilidou, Anastasia, additional, Mukhopadhyay, Subhankar, additional, Dougan, Gordon, additional, Hoed, Marcel den, additional, Loos, Ruth, additional, Fernández-Real, José Manuel, additional, Chiarugi, Davide, additional, Clément, Karine, additional, and Vidal-Puig, Antonio, additional

Published
2020
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42. CD14 modulates inflammation-driven insulin resistance

Author

Fernandez-Real, Jose Manuel, del Pulgar, Sofia Perez, Luche, Elodie, Moreno-Navarrete, Jose Maria, Waget, Aurelie, Serino, Matteo, Sorianello, Eleonora, Sanchez-Pla, Alex, Pontaque, Francesc Carmona, Vendrell, Joan, Chacon, Matilde R., Ricart, Wifredo, Burcelin, Remy, and Zorzano, Antonio

Subjects
Gene expression -- Research, Inflammation -- Genetic aspects -- Research, Insulin resistance -- Physiological aspects, Lipid metabolism -- Research, Health
Abstract

OBJECTIVE--The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance. RESEARCH DESIGN AND METHODS--The effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat-fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes. RESULTS--rh-sCD14 led to increased insulin action in WT mice, high-fat-fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not women in CD14 KO mice grafted with bone marrow stem cells from high fat-fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-α. CONCLUSIONS--CD14 modulates adipose tissue inflammatory activity and insulin resistance., Insulin resistance and chronic, low-grade inflammation are important predisposing factors for the development of type 2 diabetes and atherosclerosis. Genes and environment unequivocally induce variations in the inflammatory response that [...]

Published
2011
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45. Antimicrobial-sensing proteins in obesity and type 2 diabetes: the buffering efficiency hypothesis

Author

Moreno-Navarrete, Jose Maria and Fernandez-Real, Jose Manuel

Subjects
Obesity -- Development and progression -- Research -- Complications and side effects, Immunoproteins -- Physiological aspects -- Research, Type 2 diabetes -- Development and progression -- Research -- Complications and side effects, Health
Abstract

Obesity is well known to be associated with a cluster of metabolic diseases such as dyslipidemia, hypertension, insulin resistance, type 2 diabetes, and atherosclerosis (1). Alterations of the innate immune [...]

Published
2011
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46. OCT1 expression in adipocytes could contribute to increased metformin action in obese subjects

Author

Moreno-Navarrete, Jose Maria, Ortega, Francisco J., Rodriguez-Hermosa, Jose-Ignacio, Sabater, Monica, Pardo, Gerard, Ricart, Wifredo, and Fernandez-Real, Jose Manuel

Subjects
Obesity -- Genetic aspects, Gene expression -- Physiological aspects, Metformin -- Dosage and administration, Fat cells -- Genetic aspects, Health
Abstract

OBJECTIVE--Metformin has been well characterized in vitro as a substrate of liver-expressed organic cation transporters (OCTs). We investigated the gene expression and protein levels of OCT-1 and OCT-2 in adipose tissue and during adipogenesis and evaluated their possible role in metformin action on adipocytes. RESEARCH DESIGN AND METHODS--OCT1 and OCT2 gene expressions were analyzed in 118 adipose tissue samples (57 visceral and 61 subcutaneous depots) and during human preadipocyte differentiation. To test the possible role of OCT1 mediating the response of adipocytes to metformin, cotreatments with cimetidine (OCT blocker, 0.5 and 5 mmol/l) and metformin were made on human preadipocytes and subcutaneous adipose tissue (SAT). RESULTS--OCT1 gene was expressed in both subcutaneous and visceral adipose tissue. In both fat depots, OCT1 gene expression and protein levels were significantly increased in obese subjects. OCT1 gene expression in isolated preadipocytes significantly increased during differentiation in parallel to adipogenic genes. Metformin (5 mmol/l) decreased the expression of lipogenic genes and lipid droplets accumulation while increasing AMP-activated protein kinase (AMPK) activation, preventing differentiation of human preadipocytes. Cotreatment with cimetidine restored adipogenesis. Furthermore, metformin decreased IL-6 and MCP-1 gene expression in comparison with differentiated adipocytes. Metformin (0.1 and 1 mmol/l) decreased adipogenic and inflammatory genes in SAT. OCT2 gene expression was not detected in adipose tissue and was very small in isolated preadipocytes, disappearing during adipogenesis. CONCLUSIONS--OCT1 gene expression and protein levels are detectable in adipose tissue. Increased OCT1 gene expression in adipose tissue of obese subjects might contribute to increased metformin action in these subjects. Diabetes 60:168-176, 2011, Metformin (dimethylbiguanidine) is the most widely used drug for the treatment of type 2 diabetes (1,2). This insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but [...]

Published
2011
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47. Complement factor H is expressed in adipose tissue in association with insulin resistance

Author

Moreno-Navarrete, Jose Maria, Martinez-Barricarte, Ruben, Catalan, Victoria, Sabater, Monica, Gomez-Ambrosi, Javier, Ortega, Francisco Jose, Ricart, Wifredo, Bluher, Mathias, Fruhbeck, Gema, de Cordoba, Santiago Rodriguez, and Fernandez- Real, Jose Manuel

Subjects
Gene expression -- Health aspects -- Research, Adipose tissues -- Health aspects, Insulin resistance -- Health aspects, Health
Abstract

OBJECTIVE--Activation of the alternative pathway of the complement system, in which factor II (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS--Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS--Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS--Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances., Obesity is closely associated with a cluster of metabolic diseases, such as dyslipidemia, hypertension, insulin resistance, type 2 diabetes, and atherosclerosis (1). Adipose tissue is well known for its essential [...]

Published
2010
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