Article
Endocrinology & Metabolism
Sandip Mukherjee, Molee Chakraborty, Eliwaza N. Msengi, Jake Haubner, Jinsong Zhang, Matthew J. Jellinek, Haley L. Carlson, Kelly Pyles, Barbara Ulmasov, Andrew J. Lutkewitte, Danielle Carpenter, Kyle S. McCommis, David A. Ford, Brian N. Finck, Brent A. Neuschwander-Tetri, Anutosh Chakraborty
Summary: Defining the regulators of cell metabolism and signaling is essential for developing therapeutic strategies in obesity and NAFLD/NASH. The E3 ubiquitin ligase Ube4A has been implicated in human obesity, inflammation, and cancer, but its in vivo function and animal models are unknown. This study generated a Ube4A knockout mouse model and identified its role in obesity, insulin resistance, adipose tissue dysfunction, and NAFLD.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Maria Magdalena Montt-Guevara, Michele Finiguerra, Ilaria Marzi, Tiziana Fidecicchi, Amerigo Ferrari, Alessandro D. Genazzani, Tommaso Simoncini
Summary: D-Chiro-Ins directly affects the differentiation and function of human adipocytes, synergizing with insulin and estrogen to promote lipid and glucose storage. This research provides insights into D-Chiro-Ins actions on fat metabolism and their implications in various diseases.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Mayumi Nagashimada, Kazuki Sawamoto, Yinhua Ni, Hironori Kitade, Naoto Nagata, Liang Xu, Masuko Kobori, Naofumi Mukaida, Tatsuya Yamashita, Shuichi Kaneko, Tsuguhito Ota
Summary: The CX3CL1-CX3CR1 system is crucial in regulating inflammation, particularly in obese mice with adipose tissue inflammation and insulin resistance. Deficiency in CX3CR1 signaling leads to an increase in M1 polarized macrophages, worsening glucose tolerance and insulin resistance in obese mice. Targeting the CX3CL1-CX3CR1 system may be beneficial in treating type 2 diabetes by modulating M1/M2 macrophages.
Article
Endocrinology & Metabolism
Mayumi Nagashimada, Kazuki Sawamoto, Yinhua Ni, Hironori Kitade, Naoto Nagata, Liang Xu, Masuko Kobori, Naofumi Mukaida, Tatsuya Yamashita, Shuichi Kaneko, Tsuguhito Ota
Summary: The CX3CL1-CX3CR1 system regulates inflammation in obese mice by affecting adipose tissue macrophage recruitment and polarization, leading to insulin resistance. Deficiency in CX3CR1 signaling results in a dominant shift towards M1-polarized macrophages, exacerbating insulin resistance in obese mice. Therapies targeting CX3CL1-CX3CR1 system may be beneficial for treating type 2 diabetes by modulating M1/M2 macrophages.
Article
Multidisciplinary Sciences
Vera J. M. Nies, Dicky Struik, Sihao Liu, Weilin Liu, Janine K. Kruit, Michael Downes, Tim van Zutphen, Henkjan J. Verkade, Ronald M. Evans, Johan W. Jonker
Summary: This study found that FGF1 can increase glucose uptake in adipocytes by activating GLUT4 protein. Furthermore, prolonged exposure to FGF1 can stimulate adipocyte glucose uptake by transcription of GLUT1 protein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Pierre-Jean Cornejo, Bastien Vergoni, Mickael Ohanna, Brice Angot, Teresa Gonzalez, Jennifer Jager, Jean-Francois Tanti, Mireille Cormont
Summary: This study identifies miR-34a as a new mediator of adipocyte insulin resistance. Upregulation of miR-34a inhibits insulin signaling and decreases glucose transport, accompanied by a reduced expression of VAMP2 and an increased expression of PTP1B. Mechanistically, miR-34a decreases NAD(+) levels, thereby inhibiting Sirtuin-1 and promoting the upregulation of PTP1B. The mRNA expression of Nampt and Naprt is also decreased in adipose tissue of obese mice.
Article
Biochemistry & Molecular Biology
Yang Wang, Rongjun Wan, Chengping Hu
Summary: This study found that obesity-related neutrophilic airway inflammation in asthma is a kind of nonallergic asthma with excessive neutrophil infiltration in the airways. The research revealed that leptin/obR signaling plays an important role in the pathogenesis of obesity-related neutrophilic airway inflammation.
MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Vanessa Castelli, Laura Brandolini, Michele D'Angelo, Cristina Giorgio, Margherita Alfonsetti, Pasquale Cocchiaro, Francesca Lombardi, Annamaria Cimini, Marcello Allegretti
Summary: Type 2 diabetes mellitus is a severe public health issue worldwide, often correlated with obesity. New drugs targeting the inhibition of proinflammatory adipocytokines secretion from adipocytes may be a potential treatment approach for the disease.
Review
Endocrinology & Metabolism
Thi Kim Chung Le, Xuan Dat Dao, Dang Vung Nguyen, Duc Huy Luu, Thi Minh Hanh Bui, Thi Huong Le, Huu Thang Nguyen, Tran Ngoan Le, Toshio Hosaka, Thi Thu Thao Nguyen
Summary: The discovery of insulin in 1921 sparked research on insulin activity and insulin resistance. This mini-review synthesizes updated discoveries in this field to uncover related mechanisms and inform the development of novel applications.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Jing Tao, Xiao-Lin Yu, Yu-Juan Yuan, Xin Shen, Jun Liu, Pei-Pei Gu, Zhao Wang, Yi-Tong Ma, Guo-Qing Li
Summary: This study identified the downregulation of DMRT2 in adipose tissues of insulin-resistant subjects and insulin-resistant mouse models. Overexpression of DMRT2 improved insulin resistance in adipocytes, while knockdown of DMRT2 enhanced insulin resistance. DMRT2 interacted with FXR and positively regulated its level and transcription activity, further improving insulin resistance in adipocytes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Nutrition & Dietetics
Eunju Kim, Kazuaki Mawatari, Seung-Hee Yoo, Zheng Chen
Summary: This study demonstrates that the polyethoxylated flavonoid Nobiletin (NOB) enhances the oscillation of core clock genes in adipocytes and inhibits lipid accumulation. The activation of ROR receptors by NOB plays a crucial role in regulating adipogenic differentiation, lipogenesis, and inflammation in adipocytes.
Article
Cell Biology
Giovanny J. Martinez-Colon, Kalani Ratnasiri, Heping Chen, Sizun Jiang, Elizabeth Zanley, Arjun Rustagi, Renu Verma, Han Chen, Jason R. Andrews, Kirsten D. Mertz, Alexandar Tzankov, Dan Azagury, Jack Boyd, Garry P. Nolan, Christian M. Schuerch, Matthias S. Matter, Catherine A. Blish, Tracey L. McLaughlin
Summary: This study found that adipocytes in COVID-19 autopsy cases were infected by SARS-CoV-2, accompanied by inflammatory infiltrate. The study also revealed that SARS-CoV-2 infected adipose tissue-resident macrophages and initiated inflammatory responses. These findings suggest that SARS-CoV-2 infection in adipose tissue could contribute to the severity of COVID-19 through viral replication and induction of inflammation.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Wenqiang Chen, Qian Huang, Ekaterina Katie Lazdon, Antonio Gomes, Marisa Wong, Emily Stephens, Tabitha Grace Royal, Dan Frenkel, Weikang Cai, C. Ronald Kahn
Summary: This study shows that brain insulin signaling controls peripheral energy metabolism and plays a key role in mood and cognition regulation. The research suggests that insulin signaling in astrocytes contributes to Alzheimer's disease pathology, highlighting the potential importance of targeting insulin signaling in astrocytes for therapeutic interventions in patients with both type 2 diabetes and Alzheimer's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Environmental Sciences
Xu Hong, Yi Zhou, Zhiyuan Zhu, Yuting Li, Zuo Li, Yuheng Zhang, Xinxin Hu, Fuhai Zhu, Yong Wang, Mingliang Fang, Yichao Huang, Tong Shen
Summary: This study demonstrates a significant association between BPA exposure and risk of obesity, as well as elevated levels of IL-17A in human adipose tissue. Animal experiments further confirm that BPA exposure exacerbates weight gain, insulin resistance, and inflammation in adipose tissue. Genetically modified mice with altered IL-17A gene show reversed inflammatory response and improved insulin sensitivity. Mediation analysis in humans suggests that IL-17A plays a mediating role in the association between BPA exposure and obesity risk.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Nutrition & Dietetics
Beegum Noorjahan Shijina, Achuthan Radhika, Sainulabdeen Sherin, Prabath Gopalakrishnan Biju
Summary: The indole alkaloid vindoline from Catharanthus roseus was found to have significant improvements in insulin resistance, oxidative stress, and inflammatory responses. It enhanced glucose metabolism and increased the expression of insulin receptors, alleviating symptoms of insulin resistance.
Article
Medicine, Research & Experimental
Chandan Sona, Yu-Te Yeh, Andreas Patsalos, Laszlo Halasz, Xin Yan, Natalia L. Kononenko, Laszlo Nagy, Matthew N. Poy
Summary: Through single-cell RNA sequencing analysis, this study found increased CADM1(+) cells adjacent to CD8(+) T cells in the islets of individuals with T1D and those who were autoantibody-positive, indicating that CADM1-mediated intercellular contact may facilitate the infiltration of cytotoxic T lymphocytes and could serve as a potential therapeutic target for preventing T1D pathogenesis.
Article
Multidisciplinary Sciences
Ulrike Zinnall, Miha Milek, Igor Minia, Carlos H. Vieira-Vieira, Simon Mueller, Guido Mastrobuoni, Orsalia-Georgia Hazapis, Simone Del Giudice, David Schwefel, Nadine Bley, Franka Voigt, Jeffrey A. Chao, Stefan Kempa, Stefan Huettelmaier, Matthias Selbach, Markus Landthaler
Summary: HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs and plays an important role in the translation of ER-targeted mRNAs. Its absence leads to impaired protein synthesis and secretion, as well as decreased tumor growth.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Ellen G. Avery, Hendrik Bartolomaeus, Ariana Rauch, Chia-Yu Chen, Gabriele N'Diaye, Ulrike Loeber, Theda U. P. Bartolomaeus, Raphaela Fritsche-Guenther, Andre F. Rodrigues, Alex Yarritu, Cheng Zhong, Lingyan Fei, Dmitry Tsvetkov, Mihail Todiras, Joon-Keun Park, Lajos Marko, Andras Maifeld, Andreas Patzak, Michael Bader, Stefan Kempa, Jennifer A. Kirwan, Sofia K. Forslund, Dominik N. Mueller, Nicola Wilck
Summary: This study investigated the impact of microbial colonization on organ damage in hypertension using germ-free and colonized mice models. The results showed that the kidney is more sensitive to microbial influence, and the colonization status is associated with circulating metabolites and inflammatory cells relevant to hypertension.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mingjuan Deng, Elda Kutrolli, Anne Sadewasser, Sven Michel, Masoumeh Motamedi Joibari, Frank Jaschinski, Gunilla Olivecrona, Stefan K. Nilsson, Sander Kersten
Summary: This study aimed to investigate the efficacy and safety of silencing ANGPTL4 in the livers of mice using ASOs. The results showed that ASOs targeting ANGPTL4 effectively reduced plasma TG levels without significant safety concerns. In addition, ASOs also reduced food intake and weight gain, improved glucose tolerance, and decreased plasma cholesterol, glucose, and liver TG levels.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Urology & Nephrology
Karen Lopez-Cayuqueo, Rosa Planells-Cases, Matthias Pietzke, Anna Oliveras, Stefan Kempa, Sebastian Bachmann, Thomas J. Jentsch
Summary: The study found that all five VRAC subunits are expressed in the kidney with distinct localizations. LRRC8C is mainly found in vascular endothelial cells, LRRC8E is specific to intercalated cells, while LRRC8A, LRRC8B, and LRRC8D are prominent in the basolateral membranes of proximal tubules. Conditional deletion of LRRC8A in proximal tubules results in injury and symptoms.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Safak Bayram, Yasmin Sophiya Razzaque, Sabrina Geisberger, Matthias Pietzke, Susanne Fuerst, Carolina Vechiatto, Martin Forbes, Guido Mastrobuoni, Stefan Kempa
Summary: Cellular glutamine synthesis plays a crucial role in protecting cells from nutrient deprivation and drug resistance. By using targeted stable isotope resolved metabolomics, this study directly measured the activity of glutamine synthetase and traced the fate of glutamine derived nitrogen in the cells' biochemical network. The results highlight the importance of glutamine synthetase in overcoming glutamine depletion and the potential of dual-isotope tracing methods in medical research.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Urology & Nephrology
Johannes Holle, Hendrik Bartolomaeus, Ulrike Loeber, Felix Behrens, Theda U. P. Bartolomaeus, Harithaa Anandakumar, Moritz I. I. Wimmer, Dai Long Vu, Mathias Kuhring, Ulrike Bruening, Andras Maifeld, Sabrina Geisberger, Stefan Kempa, Fabian Schumacher, Burkhard Kleuser, Philip Bufler, Uwe Querfeld, Stefanie Kitschke, Denise Engler, Leonard D. D. Kuhrt, Oliver Drechsel, Kai-Uwe Eckardt, Sofia K. K. Forslund, Andrea Thuermer, Victoria McParland, Jennifer A. A. Kirwan, Nicola Wilck, Dominik Mueller
Summary: Patients with chronic kidney disease (CKD) exhibit a proinflammatory immune response, potentially associated with gut dysbiosis, leading to gut barrier dysfunction and microbial metabolite imbalance, which significantly influences susceptibility to cardiovascular disease.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Endocrinology & Metabolism
Alexis Z. L. Shih, Yi-Chun Chen, Thilo Speckmann, Esben Sondergaard, Annette Schuermann, C. Bruce Verchere, Thomas E. Willnow
Summary: This study reveals that the sorting-related receptor SORLA plays a protective role in pancreatic islets by preventing amyloid deposition and associated cell death caused by islet amyloid polypeptide. SORLA mediates the endocytic uptake of proIAPP, reducing the accumulation of amyloid peptides in islets.
MOLECULAR METABOLISM
(2022)
Article
Immunology
Zhirong Zhang, Rossella Venditti, Li Ran, Zengzhen Liu, Karl Vivot, Annette Schurmann, Juan S. Bonifacino, Maria Antonietta De Matteis, Romeo Ricci
Summary: The NLRP3 inflammasome plays a crucial role in the innate immune response, and disruption of the endoplasmic reticulum-endosome membrane contact sites (EECS) leads to NLRP3 accumulation in endosomes and activation of the inflammasome. Lowering endosomal phosphatidylinositol 4-phosphate (PI4P) levels prevents NLRP3 association with endosomes and inhibits inflammasome activation. This discovery helps us better understand the activation mechanism of the inflammasome.
Article
Biochemistry & Molecular Biology
Tobias Opialla, Benjamin Gollasch, Peter H. J. L. Kuich, Lars Klug, Gabriele Rahn, Andreas Busjahn, Simone Spuler, Michael Boschmann, Jennifer A. Kirwan, Friedrich C. Luft, Stefan Kempa
Summary: The study developed a blood-drop method to assess metabolism in exercising individuals. The findings suggest that glucose availability and oxidative capacity play important roles in confronting maximal exertion.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Beatriz F. Corte-Real, Ibrahim Hamad, Rebeca Arroyo Hornero, Sabrina Geisberger, Joris Roels, Lauren Van Zeebroeck, Aleksandra Dyczko, Marike W. van Gisbergen, Henry Kurniawan, Allon Wagner, Nir Yoset, Susanne N. Y. Weiss, Klaus G. Schmetterer, Agnes Schroeder, Luka Krampert, Stefanie Haase, Hendrik Bartolomaeus, Niels Hellings, Yvan Saeys, Ludwig J. Dubois, Dirk Brenner, Stefan Kempa, David A. Hafler, Johannes Stegbauer, Ralf A. Linker, Jonathan Jantsch, Dominik N. Mueller, Markus Kleinewietfeld
Summary: High salt induces metabolic reprogramming in human Tregs, leading to pro-inflammatory features and FOXP3 downregulation, which has important implications for autoimmunity.
Correction
Biochemistry & Molecular Biology
Tobias Opialla, Benjamin Gollasch, Peter H. J. L. Kuich, Lars Klug, Gabriele Rahn, Andreas Busjahn, Simone Spuler, Michael Boschmann, Jennifer A. Kirwan, Friedrich C. Luft, Stefan Kempa
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biology
Julia Loeffler, Anne Noom, Agnes Ellinghaus, Anke Dienelt, Stefan Kempa, Georg N. Duda
Summary: Bone regeneration after fracture is a complex process with high and dynamic energy demands. Metabolites, particularly succinate, are shown to play central roles as signaling molecules during the onset of healing and in steering bone tissue regeneration. Succinate is found to promote vascularization and ossification, highlighting that metabolites have the potential to be used therapeutically to promote fracture healing.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Leona Kovac, Thilo Speckmann, Markus Jaehnert, Pascal Gottmann, Louise Fritsche, Hans-Ulrich Haering, Andreas L. Birkenfeld, Andreas Fritsche, Annette Schuermann, Meriem Ouni
Summary: MicroRNAs serve as means of communication between insulin-sensitive tissues to mediate diabetes development. Using an integrated approach, let-7i-5p was identified as a potential marker of prediabetes in women.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Wenke Jonas, Oliver Kluth, Anett Helms, Sarah Voss, Markus Jahnert, Pascal Gottmann, Thilo Speckmann, Birgit Knebel, Alexandra Chadt, Hadi Al-Hasani, Annette Schuermann, Heike Vogel
Summary: Current attempts to prevent and manage type 2 diabetes have had moderate effectiveness. A recent study identified the S100z gene as a potential causal gene for the diabetes QTL Nidd13/NZO, affecting beta-cell proliferation and apoptosis. This discovery provides new insights into the molecular mechanisms of diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)