Article
Endocrinology & Metabolism
Susanna Bianzano, Andrea Henrich, Lena Herich, Brigitte Kalsch, Donald Sarubbi, Friedeborg Seitz, Thomas Forst
Summary: Two Phase I studies showed that BI 1356225, a GOAT inhibitor, was well-tolerated in healthy males and subjects with overweight/obesity. However, treatment with BI 1356225 for 28 days did not lead to significant reduction in bodyweight or changes in appetite, eating control, or energy intake.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Review
Biochemistry & Molecular Biology
Tasha R. Davis, Mariah R. Pierce, Sadie X. Novak, James L. Hougland
Summary: Ghrelin is a peptide hormone that regulates hunger and metabolism through its unique acylation process; it is the only known hormone that directly stimulates appetite and hunger signaling. Research advancements in GOAT enzymology, structural modeling, and inhibitor development have enhanced our understanding of ghrelin signaling and offer potential for therapeutic applications.
Article
Endocrinology & Metabolism
Jennifer L. Miller, Andre Lacroix, Lynne M. Bird, Ashley H. Shoemaker, Andrea Haqq, Cheri L. Deal, Kristie A. Clark, Michael H. Ames, Jeffrey G. Suico, Amparo de la Pena, Caroline Fortier
Summary: GLWL-01, a GOAT inhibitor, was evaluated for the treatment of PWS patients. The study showed that GLWL-01 effectively reduced the levels of AG and UAG, but did not significantly improve hyperphagia-related behavior or other clinical measures. The drug was well tolerated and safe.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Pharmacology & Pharmacy
Emanuela Micioni Di Bonaventura, Luca Botticelli, Fabio Del Bello, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura
Summary: Ghrelin is a potent regulator of food intake and obesity, with its functions mediated by interactions with receptors in the hypothalamic area. The two forms of ghrelin have contrasting effects on body weight and eating behaviors, and also impact the urge to eat under stressful conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Claire E. Coupland, T. Bertie Ansell, Mark S. P. Sansom, Christian Siebold
Summary: The membrane-bound O-acyltransferase (MBOAT) superfamily catalyses the transfer of acyl chains to substrates implicated in essential cellular functions. Aberrant function of MBOATs is associated with various diseases and MBOATs are promising drug targets. Recent progress in structural characterisation of MBOATs has advanced our understanding of their functional mechanism. Integration of information across the MBOAT family has identified a common MBOAT fold and provided insights into substrate and inhibitor engagement. Further studies should focus on characterising MBOATs within their membrane environment as lipid-associated proteins.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Environmental Sciences
Hyun Jun Kim, Young Jin Tak, Sang Yeoup Lee, Jeong Pyo Seo
Summary: This study investigated the effects of a 12-week diet plus exercise programme on ghrelin concentrations in girls with obesity. The results showed that the exercise programme led to a decrease in body fat percentage and an increase in DAG concentrations. However, no significant changes were observed in AG and GOAT concentrations.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Review
Physiology
Mariah R. R. Pierce, James L. L. Hougland
Summary: Acylation modifications in biological processes and their association with various health conditions have attracted much research interest. The membrane bound O-acyltransferase (MBOAT) family of enzymes play a crucial role in these modifications. Recent advancements in solubilization approaches and structural characterization techniques have provided a wealth of information on the structure and function of MBOATs, enabling a better understanding of their catalytic activity and potential therapeutic applications.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Carys S. Jones, Alexander C. Anderson, Anthony J. Clarke
Summary: The study investigates the topology of Staphylococcus aureus OatAN and the biochemical characterization of OatA, identifying a catalytic triad of Tyr-His-Glu residues. The research proposes a model for OatA action involving the translocation of acetyl groups and their intramolecular transfer for the O-acetylation of peptidoglycan.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Agriculture, Dairy & Animal Science
Christiane Storch, Herbert Fuhrmann, Axel Schoeniger
Summary: Currently, there are no therapies available to repair joint defects in equine medicine. Nasal septum hyaline cartilage may have a positive effect on damaged articular cartilage. Further research is needed to explore the potential of nasal chondrocytes for regenerative therapies in equine osteoarthritis.
Article
Biology
Yuki Uchida, Masahiko Izumizaki
Summary: Maintenance of body temperature during fasting is important for homeotherms. Ghrelin, a hormone secreted by the stomach during fasting, has different effects on thermoregulation depending on its form. Active ghrelin (AG) decreases body temperature in thermoneutral and cold conditions, but does not affect thermoregulatory behavior. In contrast, non-active ghrelin (DAG) decreases body temperature in thermoneutral and hot conditions, and facilitates thermoregulatory behavior in the cold.
JOURNAL OF THERMAL BIOLOGY
(2023)
Article
Physiology
Gaelle Boudry, Armelle Cahu, Veronique Rome, Regis Janvier, Margaux Louvois, Daniel Catheline, Vincent Rioux, Isabelle Le Huerou-Luron, Sophie Blat
Summary: The ghrelin-ghrelin receptor (GHSR1) system plays a crucial role in regulating food intake and energy balance. This study investigated the early post-natal development of the ghrelin system in mini-pigs and the impact of dietary medium-chain fatty acids (MCFA). The results showed that plasma ghrelin levels peaked at post-natal day 2, but the acylated fraction remained unchanged except in adults. The expression of the gene PCSK1/3, which is involved in ghrelin maturation, showed post-natal modifications parallel to the variations in circulating plasma ghrelin level. However, dietary MCFA did not impact this post-natal development.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Enrique Garcia-Recio, Victor J. Costela-Ruiz, Rebeca Illescas-Montes, Lucia Melguizo-Rodriguez, Olga Garcia-Martinez, Concepcion Ruiz, Elvira De Luna-Bertos
Summary: This study analyzed the effect of BPA analogs on the gene expression of osteogenic markers and found that they inhibit the expression of these markers, including COL-1, OSC, and BMP2. Further research is needed to determine the possible contribution of Bisphenol exposure to the development of bone diseases such as osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bowei Yan, Chuanyi Chang, Yingnan Gu, Nan Zheng, Yuyan Fang, Ming Zhang, Guijiang Wang, Liguo Zhang
Summary: This study characterized the Cannabis sativa DGAT gene family, which is associated with important processes like growth, environmental adaptation, and stress responses. The expression dynamics of CsDGAT genes vary in different tissues and varieties, suggesting distinct functional roles in cold responses and shaping different parts of hemp seedlings' responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Jikun Song, Wenfeng Pei, Nuohan Wang, Jianjiang Ma, Yue Xin, Shuxian Yang, Wei Wang, Quanjia Chen, Jinfa Zhang, Jiwen Yu, Man Wu, Yanying Qu
Summary: By comparative transcriptome analysis, this study reveals the gene expression network involved in oil synthesis in cottonseeds and proposes the main pathway for oil production. Additionally, GhCYSD1 is identified as a potential key player in oil biosynthesis.
PHYSIOLOGIA PLANTARUM
(2022)
Article
Multidisciplinary Sciences
Kevin Montagne, Katsuko S. Furukawa, Yuki Taninaka, Brandon Ngao, Takashi Ushida
Summary: Osteoarthritis (OA) is a common joint disease in older adults with gradual degradation of articular cartilage. Our study found that high pressure can induce gene expression changes, including the up-regulation of micro-RNAs. Furthermore, we discovered that the expression of the Mir155hg gene is regulated by high pressure through specific signaling pathways.
Article
Gastroenterology & Hepatology
Natalia da Silva Lima, Marcos F. Fondevila, Eva Novoa, Xabier Buque, Maria Mercado-Gomez, Sarah Gallet, Maria J. Gonzalez-Rellan, Uxia Fernandez, Anne Loyens, Maria Garcia-Vence, Maria Del Pilar Chantada-Vazquez, Susana B. Bravo, Patricia Maranon, Ana Senra, Adriana Escudero, Magdalena Leiva, Diana Guallar, Miguel Fidalgo, Pedro Gomes, Marc Claret, Guadalupe Sabio, Marta Varela-Rey, Teresa C. Delgado, Rocio Montero-Vallejo, Javier Ampuero, Miguel Lopez, Carlos Dieguez, Laura Herrero, Dolors Serra, Markus Schwaninger, Vincent Prevot, Rocio Gallego-Duran, Manuel Romero-Gomez, Paula Iruzubieta, Javier Crespo, Maria L. Martinez-Chantar, Carmelo Garcia-Monzon, Agueda Gonzalez-Rodriguez, Patricia Aspichueta, Ruben Nogueiras
Summary: ATG3, induced in the liver of NAFLD patients, plays a role in lipid metabolism and may contribute to the development of steatosis. Inhibition of hepatic ATG3 can improve fatty acid metabolism by reducing JNK1, leading to increased SIRT1, CPT1a, and mitochondrial function, independent of its autophagic action.
JOURNAL OF HEPATOLOGY
(2022)
Article
Rheumatology
Patricia Seoane-Collazo, Eva Rial-Pensado, Anxela Estevez-Salguero, Edward Milbank, Lucia Garcia-Caballero, Marcos Rios, Laura Linares-Pose, Morena Scotece, Rosalia Gallego, Jose Manuel Fernandez-Real, Ruben Nogueiras, Carlos Dieguez, Oreste Gualillo, Miguel Lopez
Summary: The study found that EA is associated with increased BAT thermogenesis and browning of subcutaneous WAT, leading to elevated energy expenditure. EA rats showed inhibition of hypothalamic AMPK, a key energy sensor in regulating central energy homeostasis. Specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus could reverse the effects of EA on energy balance, brown fat, and browning, as well as improve synovial inflammation in experimental arthritis.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Eloi Franco-Trepat, Ana Alonso-Perez, Maria Guillan-Fresco, Alberto Jorge-Mora, Antia Crespo-Golmar, Miriam Lopez-Fagundez, Andres Pazos-Perez, Oreste Gualillo, Susana Belen Bravo, Rodolfo Gomez Bahamonde
Summary: The study shows that the antidepressant amitriptyline can inhibit TLR4-mediated innate immune responses in human osteoarthritis chondrocytes, reducing inflammation and promoting growth effects. Clinical data suggests that amitriptyline may be repurposed for managing innate immune responses in various joint inflammatory pathologies.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Miguel Camba-Gomez, Laura Arosa, Oreste Gualillo, Javier Conde-Aranda
Summary: Despite the benefits of current therapeutic options, there is a need for novel pharmacological targets to improve the treatment of inflammatory bowel disease (IBD). Chemokine and chemokine receptors have emerged as appealing options, as they regulate leukocyte trafficking and other processes related to intestinal inflammation development.
DRUG DISCOVERY TODAY
(2022)
Review
Rheumatology
Vera Francisco, Jesus Pino, Miguel Angel Gonzalez-Gay, Francisca Lago, Jaro Karppinen, Osmo Tervonen, Ali Mobasheri, Oreste Gualillo
Summary: Studies have found that immunometabolic alterations in patients with obesity and type 2 diabetes mellitus are closely related to intervertebral disc degeneration, involving the abnormal production of proteins such as adipokines and exacerbation of inflammatory responses.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Monica Fedele, Oreste Gualillo, Andrea Vecchione
BIOMED RESEARCH INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Sandra Feijoo-Bandin, Alana Aragon-Herrera, Manuel Otero-Santiago, Laura Anido-Varela, Sandra Morana-Fernandez, Estefania Tarazon, Esther Rosello-Lleti, Manuel Portoles, Oreste Gualillo, Jose Ramon Gonzalez-Juanatey, Francisca Lago
Summary: Sodium-glucose co-transporter 2 inhibitors, known as gliflozins, not only regulate glucose homeostasis and show cardio-renal protective effects in patients with heart failure, but also have anti-inflammatory properties, which may be beneficial for treating other diseases associated with inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Djedjiga Ait Eldjoudi, Alfonso Cordero Barreal, Maria Gonzalez-Rodriguez, Clara Ruiz-Fernandez, Yousof Farrag, Mariam Farrag, Francisca Lago, Maurizio Capuozzo, Miguel Angel Gonzalez-Gay, Antonio Mera Varela, Jesus Pino, Oreste Gualillo
Summary: White adipose tissue is a specialized tissue involved in lipid synthesis and storage. It serves as an active organ that secretes hormones and cytokines called adipokines, with leptin being a key molecule. Leptin not only regulates energy balance and food intake, but also plays roles in reproduction, glucose metabolism, hematopoiesis, and immune system interactions. It is involved in innate and adaptive immunity and contributes to the pathogenesis of chronic inflammation and immune-related diseases like osteoarthritis and rheumatoid arthritis. This review summarizes recent findings on the involvement of leptin in immunity and inflammatory responses in these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Orthopedics
O. Gualillo
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Biochemistry & Molecular Biology
Veronica Pulito-Cueto, Fernanda Genre, Raquel Lopez-Mejias, Victor Manuel Mora-Cuesta, David Iturbe-Fernandez, Virginia Portilla, Maria Sebastian Mora-Gil, Javier Gonzalo Ocejo-Vinyals, Oreste Gualillo, Ricardo Blanco, Alfonso Corrales, Ivan Ferraz-Amaro, Santos Castaneda, Jose Manuel Cifrian Martinez, Belen Atienza-Mateo, Sara Remuzgo-Martinez, Miguel Angel Gonzalez-Gay
Summary: The aim of this study was to investigate the role of endothelin-1 (ET-1) as a biomarker of interstitial lung disease (ILD), and to differentiate between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD). The study included a large cohort of ILD patients and healthy controls, and found that ET-1 levels were increased in IPF and AD-ILD patients compared to controls. However, ET-1 levels could not differentiate between IPF and AD-ILD, and were associated with worse lung function in IPF and RA-ILD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ana Alonso-Perez, Maria Guillan-Fresco, Eloi Franco-Trepat, Alberto Jorge-Mora, Miriam Lopez-Fagundez, Andres Pazos-Perez, Antia Crespo-Golmar, Jose R. Caeiro-Rey, Rodolfo Gomez
Summary: The balance between adipogenesis and osteoblastogenesis is relevant in multiple diseases. Current in vitro differentiation models for human mesenchymal stem cells (hMSCs) are expensive and hardly reproducible, making it difficult to study the equilibrium between adipocytes and osteoblasts in an affordable and reliable manner. In this study, lab-made media were compared with consensus and commercial media, and a cell-line (C3H10T1/2) was identified to simultaneously evaluate both MSCs differentiations. Lab-made media significantly increased the differentiation of hMSCs into adipocytes and osteoblasts. Additionally, the lab-made media promoted adipocyte gene-markers expression in C3H10T1/2 and hMSC-TERT and osteoblast gene-markers in C3H10T1/2. The optimized lab-made media proved to be better at differentiating MSCs compared to consensus/commercial media and demonstrated the adipogenic commitment of pre-osteoblast-like cells from aged-women. C3H10T1/2 is an ideal MSC line for studying the balance between adipocytes and osteoblasts.
Article
Biochemistry & Molecular Biology
Andres Pazos-Perez, Maria Pineiro-Ramil, Eloi Franco-Trepat, Maria Guillan-Fresco, Veronica Lopez-Lopez, Alberto Jorge-Mora, Ana Alonso-Perez, Rodolfo Gomez
Summary: The study found that methylphenidate hydrochloride (MPH) may have an impact on the growth plate, leading to premature closure and growth retardation in patients with attention deficit hyperactivity disorder treated with MPH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Alessandro Ottaiano, Mariachiara Santorsola, Luisa Circelli, Anna Maria Trotta, Francesco Izzo, Francesco Perri, Marco Cascella, Francesco Sabbatino, Vincenza Granata, Marco Correra, Luca Tarotto, Salvatore Stilo, Francesco Fiore, Nicola Martucci, Antonello La Rocca, Carmine Picone, Paolo Muto, Valentina Borzillo, Andrea Belli, Renato Patrone, Edoardo Mercadante, Fabiana Tatangelo, Gerardo Ferrara, Annabella Di Mauro, Giosue Scognamiglio, Massimiliano Berretta, Maurizio Capuozzo, Angela Lombardi, Jerome Galon, Oreste Gualillo, Ugo Pace, Paolo Delrio, Giovanni Savarese, Stefania Scala, Guglielmo Nasti, Michele Caraglia
Summary: Oligometastatic disease is a condition in which cancer spreads to only a few distant sites, and it is associated with a more favorable prognosis compared to polymetastatic disease. Recent studies have identified specific molecular and genetic features that underlie the oligometastatic phenotype, suggesting the potential for personalized therapies. This scoping review highlights new clinical, biological, and methodological challenges in understanding and treating oligometastatic disease.
Article
Biology
Rodolfo Gomez, Matt J. Barter, Ana Alonso-Perez, Andrew J. Skelton, Carole Proctor, Gabriel Herrero-Beaumont, David A. Young
Summary: In this study, the relationship between DNA-methylation changes during osteoblastogenesis and the transcription factors that interact with these regions were investigated. The DNA-methylation profile of MSCs differentiated into osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. A bioinformatic tool was developed to analyze the differentially methylated regions and identify the TFs associated with them. ZEB1 TF was identified as a key mediator in adipogenesis, osteoblastogenesis, and obesity-related bone adiposity.
BIOLOGICAL RESEARCH
(2023)