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
Chemistry, Physical
Jorge C. Pereira, Artur J. M. Valente, Olle Soderman
Summary: The interaction between octanoic acid and its conjugate base sodium octanoate with α-cyclodextrin was studied using 1H NMR and isothermal titration calorimetry, respectively, at 298.15 K. The results indicate a 1:1 stoichiometry in the complex and a positive entropy in the binding of octanoate with α-cyclodextrin, highlighting the importance of hydrophobic interactions. The effect of α-cyclodextrin on the acidity behavior of the acid was evaluated using potentiometric titration, and the results suggest that octanoic acid becomes a weaker acid after complexation.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Review
Physiology
Alanna S. Thomas, Martina Sassi, Roberto Angelini, Alwena H. Morgan, Jeffrey S. Davies
Summary: Acyl-ghrelin is a unique orexigenic hormone involved in stimulating food intake and regulating energy homeostasis. Its acylation process involves binding of various saturated fatty acids and influences lipid metabolism and cognition. This review discusses the relevance of ghrelin acylation in brain physiology and pathology.
FRONTIERS IN PHYSIOLOGY
(2022)
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
Biochemistry & Molecular Biology
Maria B. Campana, Tasha R. Davis, Sadie X. Novak, Elizabeth R. Cleverdon, Michael Bates, Nikhila Krishnan, Erin R. Curtis, Marina D. Childs, Mariah R. Pierce, Yasandra Morales-Rodriguez, Michelle A. Sieburg, Heidi Hehnly, Leonard G. Luyt, James L. Hougland
Summary: Ghrelin O-acyltransferase (GOAT) plays a central role in the maturation and activation of ghrelin, a peptide hormone with diverse endocrine signaling roles. By using a specific fluorescent ghrelin-derived peptide, we demonstrate that GOAT interacts with extracellular ghrelin and facilitates its internalization in both transfected and cancer cells. Our study provides insights into the mechanism of GOAT and suggests that other peptide hormones may have similar intercellular signaling pathways.
ACS CHEMICAL BIOLOGY
(2023)
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)
Article
Biochemistry & Molecular Biology
Emily S. Murzinski, Ishika Saha, Hui Ding, David Strugatsky, Ryan A. Hollibaugh, Haixia Liu, Peter Tontonoz, Patrick G. Harran
Summary: Ghrelin is a hormone that plays a crucial role in regulating food intake, growth hormone secretion, and insulin secretion. A medicinal chemistry campaign led to the discovery of small lipopeptidomimetics that inhibit GOAT in vitro. The study also synthesized heterocyclic inhibitors that compete at the acyl coenzyme A binding site.
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
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)
Article
Chemistry, Medicinal
Pinaki Bhattacharjee, Nicholas Rutland, Malliga R. Iyer
Summary: This article summarizes the literature on various SOAT inhibitory agents and discusses the design, structural requirements, and mode of action of SOAT inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Food Science & Technology
Shaohua Liang, Quan Zhao, Xianzhi Wei, Cong Sun
Summary: In this study, chlorogenic oleate (CGO) was efficiently synthesized through acylation of chlorogenic acid (CGA) and oleoyl chloride. By optimizing the reaction conditions, the researchers successfully obtained a high purity product. The best synthesis conditions, including substrate molar ratio, adding method, reaction time, and temperature, were determined through experiments.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Chul-Jin Lee, Robyn Stix, Mitra S. Rana, Flowreen Shikwana, R. Elliot Murphy, Rodolfo Ghirlando, Jose D. Faraldo-Gomez, Anirban Banerjee
Summary: S-acylation, also known as palmitoylation, is a common form of protein lipidation in humans. DHHC enzymes use palmitoyl CoA as a substrate for protein acylation, with the interaction of both the fatty acyl chain and the CoA headgroup being crucial for catalytic chemistry.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Organic
Eman A. Ahmed, Khaled M. Mohamed, Shymaa A. Thabet, Amr H. Moustafa, Ahmed F. Mabied, Ahmed Khodairy
Summary: N-Acylation and O-acylation of pseudoephedrine using aroyl chlorides and ethyl chloroformate as acylating agents were investigated. Reaction of pseudoephedrine with benzoyl or p-nitrobenzoyl chlorides resulted in the corresponding N- or O-acylated products 2a, b, 3a, b and 4. Furthermore, pseudoephedrine reacted with ethoxymethylenemalononitrile to yield 2-hydroxy-1-methyl-2-phenylethyl](methyl)amino}methylene)malononitrile (5). New oxazolidine derivatives 6a-c were synthesized in high yields by reacting 1 with different bis(methylthio)yledinenitriles. X-ray crystallographic study of 4 revealed its crystallization in an orthorhombic system with stabilized structure through intermolecular interactions and hydrogen bond contacts.
SYNTHETIC COMMUNICATIONS
(2023)
Article
Microbiology
E-Ming Rau, Zdenka Bartosova, Kare Andre Kristiansen, Inga Marie Aasen, Per Bruheim, Helga Ertesvag
Summary: Thraustochytrids are marine eukaryotes that accumulate high amounts of triacylglycerols and synthesize terpenoids like carotenoids and squalene. This study characterizes two putative DGAT2 genes in Aurantiochytrium sp. T66 and their homologs in Aurantiochytrium limacinum SR21. The results show the functional diversity of DGAT2-like proteins and provide valuable information on steryl ester and squalene synthesis in thraustochytrids, paving the way to enhance squalene production through metabolic engineering.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Nutrition & Dietetics
Christina Heidt, Manfred Fobker, Mary Newport, Reinhold Feldmann, Tobias Fischer, Thorsten Marquardt
Summary: This single-center study investigated the impact of consuming carbohydrate as glucose with MCT oil compared to MCT alone on the BHB response. The results showed that consuming MCT oil alone significantly increased BHB levels, while consuming MCT oil with glucose delayed the peak of BHB and led to increased blood glucose and insulin levels.
Article
Nutrition & Dietetics
Simon Bucher, Karima Begriche, Daniel Catheline, Viviane Trak-Smayra, Francois Tiaho, Cedric Coulouarn, Gregory Pinon, Dominique Lagadic-Gossmann, Vincent Rioux, Bernard Fromenty
EUROPEAN JOURNAL OF NUTRITION
(2020)
Review
Biochemistry & Molecular Biology
Etienne Guillocheau, Philippe Legrand, Vincent Rioux
Article
Food Science & Technology
Etienne Guillocheau, Gaetan Drouin, Daniel Catheline, Clement Orione, Philippe Legrand, Vincent Rioux
EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY
(2020)
Review
Pediatrics
P. Tounian, M. Bellaiche, P. Legrand
Summary: The regulation by the European Commission makes DHA a mandatory nutrient in infant formulae, raising concerns among global scientific experts about potential health risks of formulas containing only DHA. Both DHA and ARA are crucial for infant development and should maintain a balanced presence in formulae for optimal growth and development.
ARCHIVES DE PEDIATRIE
(2021)
Article
Biochemistry & Molecular Biology
Pierre Weill, Claire Plissonneau, Philippe Legrand, Vincent Rioux, Ronan Thibault
Editorial Material
Biochemistry & Molecular Biology
Vincent Rioux, Michel Record
Review
Medicine, Research & Experimental
Philippe Legrand, Daniel Catheline, Vincent Rieux
Summary: After a long and dogmatic period demonizing dietary lipids, scientists have proposed a new paradigm and rehabilitation for lipids, which has been endorsed by French guidelines since 2010, with recent data confirming the importance of this approach for infants.
M S-MEDECINE SCIENCES
(2021)
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
Thomas Guerbette, Martin Beaumont, Mireille Andriamihaja, Vincent Ciesielski, Jean-Baptiste Perrin, Regis Janvier, Gwenaelle Randuineau, Patricia Leroyer, Olivier Loreal, Vincent Rioux, Gaelle Boudry, Annaig Lan
Summary: Obesity is associated with inflammation, intestinal imbalance, and dysbiosis of the microbiota. This study aimed to investigate the effect of an obesogenic diet on mitochondrial function in colonic epithelial cells (CEC) of mice. The results showed that mice on the obesogenic diet developed obesity, intestinal hyperpermeability, and increased endotoxemia. Mitochondrial dysfunction, characterized by decreased respiration and lower ATP production, was observed in CEC of these mice. Additionally, increased sulfide production and altered bile acid concentrations were found in the colonic content of obese mice. Chronic treatment of control mouse colon organoids with sodium sulfide induced similar mitochondrial dysfunction, while acute exposure of isolated mitochondria from control mice to sodium sulfide decreased complex IV activity. These findings suggest that dysbiosis-induced sulfide production impairs mitochondrial function in CEC of obese mice.
Article
Nutrition & Dietetics
Justine Marchix, Charlene Alain, Sandrine David-Le Gall, Luis Alberto Acuna-Amador, Celine Druart, Nathalie M. Delzenne, Frederique Barloy-Hubler, Philippe Legrand, Gaelle Boudry
Article
Chemistry, Applied
Etienne Guillocheau, Clemence Penhoat, Gaetan Drouin, Ambre Godet, Daniel Catheline, Philippe Legrand, Vincent Rioux
