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Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

List by Pablo Ranea Robles

Preprints:

Pioglitazone rescues mitochondrial lipid remodeling and pyruvate dehydrogenase hyperactivation in hepatic insulin resistance

Chris E. Shannon, Mukundan Ragavan, Juan Pablo Palavicini, Marcel Fourcaudot, Terry Bakewell, Eunsook S. Jin, Craig R. Malloy, Xianlin Han, Matthew E. Merritt, Luke Norton

https://www.biorxiv.org/content/10.1101/2020.01.02.892992v1

Pioglitazone is an insulin-sensitizing drug prescribed for Type II Diabetes whose beneficial effects are usually associated to adipose tissue PPAR-gamma targeting. In this preprint, Shannon et al. investigated the effects of pioglitazone on hepatic mitochondrial remodeling. They found that the beneficial effects of pioglitazone in mice are dissociated from changes in TG and DAG levels in the liver. Instead, pioglitazone targeted mitochondrial lipids such as cardiolipin and inhibited PDH activation.

mTORC1-Plin3 pathway is essential to activate lipophagy and protects against hepatosteatosis

Marina Garcia-Macia, Adrián Santos-Ledo, Jack Leslie, Hanna Paish, Abigail Watson, Lee Borthwick, Jelena Mann, Fiona Oakley, Viktor I. Korolchuk, Derek A. Mann

https://www.biorxiv.org/content/10.1101/812990v1

Excess of lipids is accumulated in hepatocytes in the form of lipid droplets (LDs), but aberrant accumulation of LDs is detrimental and is involved in diseases like NAFLD. One way to relieve lipotoxicity is to degrade LDs by autophagy (lipophagy). Here, García-Macia et al. show that Plin3, a member of the perilipin family of proteins that coat LDs, is also involved in LD autophagy. They also show that mTORC1 phosphorylates and, surprisingly, activates Plin3 and lipophagy. Silencing of Plin3 inhibited lipophagy and induced lipid accumulation.

Transcriptomic Profiling of Skeletal Muscle Adaptations to Exercise and Inactivity

Nicolas J. Pillon, Brendan M. Gabriel, Lucile Dollet, Jonathon A. Smith, Laura Sardón Puig, Javier Botella, David J. Bishop, Anna Krook, Juleen R. Zierath

https://www.biorxiv.org/content/10.1101/813048v1

To better understand the transcriptomic changes underlying the adaptations in skeletal muscle to exercise and sedentarism Pillon et al. integrated data from 66 published datasets. This extensive compilation of transcriptomics data revealed different pathways activated by inactivity, different types of exercise and different modes of training. NR4A3 (Nor1) was identified as one of the most responsive genes to exercise and inactivity. They also provide an online interface to explore the database.

PHGDH supports liver ceramide synthesis and sustains lipid homeostasis

Yun Pyo Kang, Aimee Falzone, Min Liu, James J. Saller, Florian A. Karreth, Gina M. DeNicola

https://www.biorxiv.org/content/10.1101/838482v1

D-3-phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step of de novo biosynthesis of L-serine. PHGDH has been proposed as an attractive target for cancer therapy since PHGDH activity is consistently high in many cancers. In this work, Kang et al. knocked down PHGDH in non-CNS adult murine tissues with a PHGDH shRNA under the control of a doxycycline-inducible promoter. There was no overt phenotype in adult tissues after PHGDH depletion. Moreover, serum and hepatic ceramide levels were decreased and triglycerides with longer and unsaturated acyl chains were increased. This work suggest that PHGDH inhibitors could be well tolerated for cancer therapy.

Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation

Natasha H. J. Ng, Sara M. Willems, Juan Fernandez, Rebecca S. Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Jana K. Rundle, Xueling Sim, Hanieh Yeghootkar, Nicola L. Beer, Anne Raimondo, Andrei I. Tarasov, Soren K. Thomsen, Martijn van de Bunt, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Hugoline G. de Haan, Niels Grarup, Ruifang Li-Gao, Tibor V. Varga, Jennifer L Asimit, Shuang Feng, Rona J. Strawbridge, Erica L. Kleinbrink, Tarunveer S. Ahluwalia, Ping An, Emil V. Appel, Dan E Arking, Juha Auvinen, Lawrence F. Bielak, Nathan A. Bihlmeyer, Jette Bork-Jensen, Jennifer A. Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S. Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Benoit Hastoy, Anne U. Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Richard A. Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Jin Li, Man Li, Kurt Lohman, Yingchang Lu, Jian’an Luan, Alisa K. Manning, Jonathan Marten, Carola Marzi, Karina Meidtner, Dennis O. Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M. Rice, Neil Robertson, Serena Sanna, Yuan Shi, Albert Vernon Smith, Jennifer A. Smith, Lorraine Southam, Heather M. Stringham, Salman M. Tajuddin, Vinicius Tragante, Sander W. van der Laan, Helen R. Warren, Jie Yao, Andrianos M. Yiorkas, Weihua Zhang, Wei Zhao, Emma Ahlqvist, Mariaelisa Graff, Heather M. Highland, Anne E Justice, Ken Sin Lo, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W. Asselbergs, Lori L. Bonnycastle, Michiel L. Bots, Ivan Brandslund, Ji Chen, Cramer Christensen, John Danesh, Renée de Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, EPIC-InterAct Consortium, Aliki-Eleni Farmaki, Jessica D. Faul, Paul W. Franks, Steve Franks, Andreas Fritsche, Anette P. Gjesing, Mark O. Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B. Harris, Karl-Heinz Herzig, Marie-France Hivert, Jan-Håkan Jansson, Min A Jhun, Torben Jørgensen, Marit E. Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L.R. Kardia, Leena Kinnunen, Heikki A. Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A. Lange, Lenore J. Launer, Jung-Jin Lee, Aaron Leong, Jaana Lindström, Jocelyn E. Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A. Nalls, Matthew Neville, James S. Pankow, Alison Pattie, Eva R.B. Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D. Taylor, Betina H. Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I. Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P. Bottinger, Mark J. Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Anne Clark, Francis S. Collins, Josef Coresh, Francesco Cucca, Gert J. de Borst, Ian J. Deary, George Dedoussis, Panos Deloukas, Hester M. den Ruijter, Josée Dupuis, Michele K. Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Leif Groop, Torben Hansen, Andrew T. Hattersley, Caroline Hayward, Joel N. Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J.F. Loos, Patrick E. MacDonald, Karen L. Mohlke, Andrew D Morris, Patricia B. Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A. Peyser, Ozren Polasek, David Porteous, Michael A. Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R. Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B. Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M. Starr, Michael Stumvoll, Cornelia M van Duijn, Mark Walker, Nick J. Wareham, David R. Weir, James G. Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B. Zonderman, Jerome I. Rotter, Andrew P. Morris, Michael Boehnke, Jose Florez, Mark I McCarthy, James B Meigs, Anubha Mahajan, Robert A. Scott, Anna L Gloyn, Inês Barroso

https://www.biorxiv.org/content/10.1101/790618v1

The metabolism of glucose is altered by metabolic dysregulation in multiple tissues. One of the main medical problems, type 2 diabetes (T2D), is caused by alterations in glucose metabolism. Ng et al. analyzed exome-array variants in 144,060 individuals without diabetes and their association with glycemic traits relevant to T2D. They found novel assocations at 21 coding variants in 18 novel loci. Their integration of genomic and functional data at multi-tissue level can offer relevant information to infer biological mechanisms in type 2 diabetes.

Integration of high-content fluorescence imaging into the metabolic flux assay reveals insights into mitochondrial properties and functions

Andrew C. Little, Ilya Kovalenko, Laura E. Goo, Hanna S. Hong, Samuel A. Kerk, Joel A. Yates, Vinee Purohit, David B. Lombard, Sofia D. Merajver, Costas A. Lyssiotis

https://www.biorxiv.org/content/10.1101/758110v1

Little et al. show here a method to integrate cellular metabolism studies with SeaHorse together with fluorescent dyes that allow to add information about mitochondrial dynamics and mitochondrial function.

ER stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress

Nurulain Ho, Haoxi Wu, Jiaming Xu, Jhee Hong Koh, Wei Sheng Yap, Wilson Wen Bin Goh, Shu Chen Chong, Stefan Taubert, Guillaume Thibault

https://www.biorxiv.org/content/10.1101/774133v1

The unfolded protein response (UPR) is an important mechanism to maintain homeostasis against misfolded proteins. However, alterations in lipid metabolism and composition have been linked to an activation of the UPR and ER stress. Here, Ho et al. uncovered a distinct UPR against lipid stress, caused by modifications in the lipid composition of ER membrane. This mechanism is conserved in yeasts and C. elegans, and involves the UPR transducer protein IRE1.

Modulation of muscle cell Insr and insulin receptor signaling by hyperinsulinemia in vitro and in vivo

Haoning Howard Cen, José Diego Botezelli, Su Wang, James D. Johnson

https://www.biorxiv.org/content/10.1101/556571v2

This preprint shed light on the mechanism of insulin resistance and its relation to hyperinsulinemia in muscle cells. They show that insulin receptor (Insr) levels were negatively correlated to insulin levels in muscle cells and mouse skeletal muscle, which suggest that hyperinsulinemia causes insulin resistance rather than being a compensatory mechanism.

mTORC1 signaling is not essential for the maintenance of muscle mass and function in adult sedentary mice

Alexander S Ham, Kathrin Chojnowska, Lionel A Tintignac, Shuo Lin, Alexander Schmidt, Daniel J Ham, Michael Sinnreich, Markus A Ruegg

https://www.biorxiv.org/content/10.1101/736538v1

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of protein homeostasis in the muscle. Rapamycin, an mTOR inhibitor, is widely used but its effect on muscle mass are not well known yet. To elucidate the role of mTORC1 in maintaining muscle mass in adulthood, Ham et al. inhibited mTORC1 signaling in the skeletal muscle of adult mice. They inhibited mTORC1 by ablating Raptor, a regulator of mTORC1 signaling. They found that muscle mass and function were not affected at 5 months of age, suggesting that muscle maintenance in sedentary mice does not require mTORC1 activity.

Lecithin:Retinol Acyl Transferase (LRAT) induces the formation of lipid droplets

Martijn R. Molenaar, Tsjerk A. Wassenaar, Kamlesh K. Yadav, Alexandre Toulmay, Muriel C. Mari, Lucie Caillon, Aymeric Chorlay, Maya W. Haaker, Richard W. Wubbolts, Martin Houweling, A. Bas Vaandrager, Fulvio Reggiori, Abdou Rachid Thiam, William A. Prinz, J. Bernd Helms

https://www.biorxiv.org/content/10.1101/733931v1

The interplay between mitochondria and the endoplasmic reticulum (ER) is essential for a proper lipid metabolism. These organelles exchange lipids at membrane contact sites, but the mechanisms and the proteins involved in this exchange are poorly understood, especially in mammals. Here, Rochin et al. show that two oxysterol binding protein (OSBP)-related proteins, ORP5 and ORP8, mediate non-vesicular transport of phosphatidylserine and, only ORP5, calcium from the ER to mitochondria in mammalian cells.

Ammonia inhibits energy metabolism in astrocytes in a rapid and GDH2-dependent manner

Leonie Drews, Erik Puskas, Nicole Dubilier, Manuel Liebeke

https://www.biorxiv.org/content/10.1101/683763v2

Seamet, a new metabolomics method to measure metabolites in seawater using GC/MS is described in this preprint. This method overcomes the limitations of salt in marine metabolomics.

Housing temperature influences exercise training adaptations in mice

Steffen H. Raun, Carlos H. Henriquez-Olguin, Iuliia Karavaeva, Mona Ali, Lisbeth L.V. Moller, Witold Kot, Josue L. Castro Mejia, Dennis Sandris Nielsen, Zach Gerhart-Hines, Erik A. Richter, Lykke Sylow

https://www.biorxiv.org/content/10.1101/651588v1

Another report on different physiological response of rodents under different housting temperatures.  Raun et al. show here that exercise-induced metabolic adaptations were blunted when mice were housed in thermoneutral conditions (30 °C).

Exercise does not induce browning of WAT at thermoneutrality and induces an oxidative, myogenic signature in BAT

Peter Aldiss, Jo E Lewis, Irene Lupini, David J Boocock, Amanda K Miles, Francis J P Ebling, Helen Budge, Michael E Symonds

https://www.biorxiv.org/content/10.1101/649061v1

Rodents are usually housed below their thermoneutral zone, but studies done at thermoneutrality show that their physiology is completely different, because brown adipose tissue (BAT) is hyperactive below thermoneutrality. Aldiss et al. show here that exercise does not induce browing of white adipose tissue (WAT) and a different response in BAT in rats housed at thermoneutrality (28 °C).

Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III

Chi-Lun Chang, Aubrey V. Weigel, Maria S. Ioannou, H. Amalia Pasolli, C. Shan Xu, David R. Peale, Gleb Shtengel, Melanie Freeman, Herald F. Hess, Craig Blackstone, Jennifer Lippincott-Schwartz

https://www.biorxiv.org/content/10.1101/544023v1

Peroxisomes interact with other organelles within the cell, but how they do it remain largely unknown. Here Chang et al. describe a tether between peroxisomes and lipid droplets that transfer fatty acids.

Presynaptic boutons that contain mitochondria are more stable

Robert M. Lees, James D. Johnson, Michael C. Ashby

https://www.biorxiv.org/content/10.1101/580530v1

Mitochondria are crucial for energy generation in the central nervous system and their dysfunction is related to multiple neurodegenerative diseases. Here, Lees et al. show that presynapses with more mitochondria are more stable, which open new avenues of research on the role of cellular metabolism and bioenergetics on synaptic structural plasticity.

Mitochondria form cholesterol tethered contact sites with the Nucleus to regulate retrograde response

Radha Desai, Daniel A East, Liana Hardy, James Crosby, Manuel Rigon, Danilo Faccenda, María Soledad Alvarez, Arti Singh, Marta Mainenti, Laura Kuhlman Hussey, Robert Bentham, Gyorgy Szabadkai, Valentina Zappulli, Gurtej Dhoot

https://www.biorxiv.org/content/10.1101/445411v2

Mitochondria and lysosomes are key organelles in lipid metabolism. Here, Faisal et al. show that mitochondrial biogenesis program is repressed in lysosomal storage disorders (LSDs), giving a plausible explanation of the mitochondrial defects usually found in patients with LSDs.

Categories: biochemistry , cell biology , pathology , physiology

Tags: lipid , metabolism , mitochondria , peroxisome

Posted on: 21st May 2019 , updated on: 14th January 2020

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