Article
Medicine, Research & Experimental
Isabella Gaziano, Svenja Corneliussen, Nasim Biglari, Rene Neuhaus, Linyan Shen, Tamara Sotelo-Hitschfeld, Paul Klemm, Lukas Steuernagel, Alain J. De Solis, Weiyi Chen, F. Thomas Wunderlich, Peter Kloppenburg, Jens C. Bruening
Summary: This study reveals the differential effects of dopamine on neurons in the hypothalamic arcuate nucleus, with activation of food intake-promoting neurons and inhibition of anorexigenic neurons. By targeting specific POMC neurons, it is found that dopamine-mediated inhibition of feeding depends on the Drd2 receptor, and POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators. Chemogenetic activation of POMCDrd2+ neurons can suppress feeding and maintain body temperature.
Article
Medicine, Research & Experimental
Longlong Tu, Jonathan C. Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A. Scarcelli, Kristine M. Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu
Summary: Glucose-inhibited neurons paradoxically increase firing activity in low-glucose conditions and decrease in high-glucose conditions. This study reveals that the Ano4 channel mediates the electric responses of these neurons to glucose fluctuations.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Maria Jose Ortuno, Marc Schneeberger, Anoj Ilanges, Francois Marchildon, Kyle Pellegrino, Jeffrey M. Friedman, Patricia Ducy
Summary: Long-term use of selective serotonin reuptake inhibitor (SSRI) antidepressants is associated with weight gain, potentially increasing the risk of obesity. The study shows that fluoxetine affects signaling pathways in the brainstem and hypothalamus, leading to increased food intake and weight gain in healthy mice.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Endocrinology & Metabolism
Andrew I. Sullivan, Meghan C. Naber, Kyle H. Flippo, Donald A. Morgan, Tate J. Neff, Sharon O. Jensen -Cody, Zhiyong Zhu, Leonid V. Zingman, Kamal Rahmouni, Matthew J. Potthoff
Summary: This study reveals the importance of the endocrine crosstalk between liver-and adipose-derived signals in the central nervous system for the regulation of energy homeostasis and body weight. FGF21 signaling to glutamatergic neurons and leptin receptor-expressing cells is necessary for FGF21 to modulate energy expenditure and promote weight loss. Co-administration of FGF21 and leptin synergistically leads to robust weight loss.
MOLECULAR METABOLISM
(2022)
Article
Endocrinology & Metabolism
Alexandre Picard, Salima Metref, David Tarussio, Wanda Dolci, Xavier Berney, Sophie Croizier, Gwenael Labouebe, Bernard Thorens
Summary: Fgf15 neurons play a crucial role in the counterregulatory response to hypoglycemia by directly affecting hepatic glucose production and suppressing vagally induced glucagon secretion.
Article
Cell Biology
Nal Ae Yoon, Sungho Jin, Jung Dae Kim, Zhong Wu Liu, Qiushi Sun, Rebecca Cardone, Richard Kibbey, Sabrina Diano
Summary: Lactate activates POMC neurons through redox signaling and blocking mitochondrial glucose utilization to regulate feeding and glucose metabolism.
Article
Medicine, Research & Experimental
Zhenyan He, Linh Lieu, Yanbin Dong, Sadia Afrin, Dominic Chau, Anita Kabahizi, Briana Wallace, Jianhong Cao, Eun-Sang Hwang, Ting Yao, Yiru Huang, Jennifer Okolo, Bo Cheng, Yong Gao, Ling Hu, Kevin W. Williams
Summary: The study showed that PERK deficiency in POMC neurons in male mice may protect against diet-induced obesity, while attenuating the improvements in leptin sensitivity and energy balance induced by celastrol.
Review
Neurosciences
Zhaoxun Liu, Tao Xiao, Hailan Liu
Summary: Leptin plays a critical role in regulating appetite, energy expenditure, and body weight, and is important for maintaining a healthy balance. Despite efforts to understand its mechanisms and develop therapeutic interventions, the effectiveness of targeting leptin signaling has been limited. In addition to the hypothalamus, other brain regions are also being increasingly investigated for their involvement in mediating leptin's effects.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Bo Chang, Chenglin Song, Haining Gao, Tie Ma, Tao Li, Qianhe Ma, Tingting Yao, Meng Wang, Jing Li, Xuejie Yi, Donghui Tang, Shicheng Cao
Summary: This study found that moderate exercise can improve the expression of kisspeptin and GnRH in the hypothalamus of obese mice, reduce inflammation levels, and improve sperm quality; while high-load exercise may promote inflammation, affecting the regulation of kisspeptin and the HPT axis.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2021)
Review
Physiology
Charles A. LeDuc, Alicja A. Skowronski, Michael Rosenbaum
Summary: This article discusses the pleiotropic gene LEP and how leptin's actions go beyond just signaling the size of adipose tissue stores. It emphasizes the prenatal, perinatal, and postnatal effects of leptin on systems regulating energy stores and the importance of therapeutic manipulation of the intrauterine environment. The review suggests that future research should focus on using leptin sensitizing agents and identifying specific cohorts that may respond better to activating the leptin signaling pathway.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Macarena Pozo, Maria Mila-Guasch, Roberta Haddad-Tovolli, Mehdi Boutagouga Boudjadja, Inigo Chivite, Miriam Toledo, Alicia G. Gomez-Valades, Elena Eyre, Sara Ramirez, Arnaud Obri, Inbal Ben-Ami Bartal, Giuseppe DAgostino, Joan Costa-Font, Marc Claret
Summary: The internal state of an animal, including homeostatic requirements, modulates its behavior. Negative energy balance stimulates hunger and affects prosocial behavior. In a study with mice, researchers found that the energy status influenced their willingness to help a trapped conspecific. This behavior was associated with changes in corticosterone and was energy-demanding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Physiology
Huibao Chen, Hao Zhang, Ting Jia, Zhengkun Wang, Wanlong Zhu
Summary: Leptin is involved in the regulation of energy metabolism and thermoregulation in Eothenomys miletus, and thyroid hormone plays an important role in the process of leptin regulating energy balance in E. miletus.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pediatrics
Liran Tamir-Hostovsky, Julijana Ivanovska, Eleana Parajon, Rachana Patel, Huanhuan Wang, George Biouss, Nikola Ivanovski, Jaques Belik, Agostino Pierro, Gaspard Montandon, Estelle B. Gauda
Summary: Exogenous leptin improves hypercapnic respiratory response in newborn rats after the 3rd week of life. However, it does not have an effect during the first week of life, suggesting that low plasma leptin levels in premature infants may not be contributing to respiratory instability.
PEDIATRIC RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C. Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R. Arenkiel, Cheng Huang, Qingchun Tong
Summary: Inhibition of hypothalamic melanocortin action leads to obesity, while chronic activation does not cause weight loss. The bidirectional regulation of body weight by melanocortin action cannot explain the difficulty in finding effective therapeutics for general obesity. This study demonstrates that altered melanocortin action is one-directional, with chronic inhibition causing obesity but chronic activation failing to reduce body weight. These findings provide a neural basis for the predisposition to obesity development and the bias of melanocortin action towards protecting weight loss.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Ngoc N. Nguyen, Ruma G. Singh, Maxim S. Petrov
Summary: Fasting levels of leptin and the leptin/ghrelin ratio are significantly associated with excess intrapancreatic fat deposition, while postprandial levels of these hormones show no significant association.
ANNALS OF NUTRITION AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Alessia Costa, Minrong Ai, Nicolas Nunn, Isabella Culotta, Jenna Hunter, Mehdi Boutagouga Boudjadja, Lourdes Valencia-Torres, Gabriella Aviello, David J. Hodson, Brandy M. Snider, Tamer Coskun, Paul J. Emmerson, Simon M. Luckman, Giuseppe D'Agostino
Summary: The study identified that cholecystokinin-expressing neurons in the caudal brainstem are crucial for the effects of GLP-1RAs and provide a novel framework for understanding and ameliorating GLP-1RA-induced nausea.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Sarajo K. Mohanta, Li Peng, Yuanfang Li, Shu Lu, Ting Sun, Lorenzo Carnevale, Marialuisa Perrotta, Zhe Ma, Benjamin Forstera, Karen Stanic, Chuankai Zhang, Xi Zhang, Piotr Szczepaniak, Mariaelvy Bianchini, Borhan R. Saeed, Raimondo Carnevale, Desheng Hu, Ryszard Nosalski, Fabio Pallante, Michael Beer, Donato Santovito, Ali Erturk, Thomas C. Mettenleiter, Barbara G. Klupp, Remco T. A. Megens, Sabine Steffens, Jaroslav Pelisek, Hans-Henning Eckstein, Robert Kleemann, Livia Habenicht, Ziad Mallat, Jean-Baptiste Michel, Jurgen Bernhagen, Martin Dichgans, Giuseppe D'Agostino, Tomasz J. Guzik, Peder S. Olofsson, Changjun Yin, Christian Weber, Giuseppe Lembo, Daniela Carnevale, Andreas J. R. Habenicht
Summary: This study discovered the presence of widespread neuroimmune cardiovascular interfaces (NICIs) in the adventitia of atherosclerosis-diseased arteries, suggesting a direct interaction between the peripheral nervous system and diseased arteries. Through anatomical and functional studies, it was found that NICIs play a crucial role in the formation of an artery-brain circuit (ABC). Therapeutic intervention in the ABC was shown to attenuate atherosclerosis.
Article
Biochemical Research Methods
Peter-Philip M. Booth, Don T. Lamb, Jon P. Anderson, Michael D. Furtaw, Robert T. Kennedy
Summary: In this study, a novel Western blotting system using capillary gel electrophoresis was developed for protein separation and quantification. This system offers advantages of easy operation and reduced sample requirements, and was successfully applied in detecting multiple proteins.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Chemistry, Analytical
Cara I. D'Amico, Daniel A. Polasky, Daniel J. Steyer, Brandon T. Ruotolo, Robert T. Kennedy
Summary: This study explores the high-throughput capabilities of CIU fingerprinting and applies it to compound screening against Sirtuin-S. The results identify novel Sirtuin-S binders and demonstrate that Sirtuin-S inhibitors stabilize specific gas-phase conformations. The study demonstrates the feasibility of droplet-CIU as a high-throughput biophysical characterization approach.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mehdi Boutagouga Boudjadja, Isabella Culotta, Gabriela C. De Paula, Erika Harno, Jenna Hunter, Joao Paulo Cavalcanti-de-Albuquerque, Simon M. Luckman, Matthew Hepworth, Anne White, Gabriella Aviello, Giuseppe D'Agostino
Summary: This study reveals the immunoregulatory functions of hypothalamic AgRP neurons in negative energy balance and endotoxemia. Endotoxemia sustains the activity of AgRP neurons and reduces their sensitivity to inhibitory signals. The study also highlights the role of endogenous glucocorticoids in this process.
Article
Biochemical Research Methods
Ashley E. E. Lenhart, Robert T. T. Kennedy
Summary: This article reports a microfluidic platform for monitoring cell secretions, which allows simultaneous measurement of insulin, glucagon, biogenic amines, and amino acids. This platform reduces the number of required samples and increases the information content achievable from one sample.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Joshua D. Jones, Kathleen T. Grassmyer, Robert T. Kennedy, Kristin S. Koutmou, Todd D. Maloney
Summary: siRNA therapeutics provide a selective and powerful approach to reduce the expression of disease-causing genes. A bottom-up siRNA sequencing platform was developed using nuclease P1, which enables easier sequencing data analysis and provides full sequence coverage. This enzymatic digestion scheme shows high-quality and highly reproducible RNA sequencing, regardless of the siRNA modifications, making it suitable for existing sequence confirmation workflows.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Emory M. Payne, Maryam Taraji, Bridget E. Murray, Daniel A. Holland-Moritz, Jeffrey C. Moore, Paul R. Haddad, Robert T. Kennedy
Summary: Droplet microfluidics allows high-throughput experimentation by encapsulating samples in aqueous droplets. However, small molecules can transport between droplets, limiting the results obtained using fluorescent molecules. This study used ESI-MS to measure the transport of low molecular weight compounds between droplets and developed a predictive tool based on the analytes tested. The transport was found to depend on carrier fluids, surfactants, and flow conditions, and can be reduced through experimental design and surfactant tailoring.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Cara I. D'Amico, Gillian Robbins, Iris Po, Zhichao Fang, Thomas R. Slaney, Gabi Tremml, Li Tao, Brandon T. Ruotolo, Robert T. Kennedy
Summary: Clone selection and cell culture optimization for protein therapeutics require screening a large number of samples. This study developed a droplet microfluidics coupled to mass spectrometry workflow for high-throughput mAb titer screening to guide clone selection.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemistry & Molecular Biology
Joshua D. Jones, Kaley M. Simcox, Robert T. Kennedy, Kristin S. Koutmou
Summary: Among all RNAs, transfer RNAs (tRNAs) have the highest variety of chemical modifications. These modifications are crucial for tRNAs to participate in protein synthesis and maintain proper structure, recognition, and reading frame maintenance. It is now known that tRNA modifications can change dynamically in response to cellular environment. Characterizing the fluctuating tRNA modification landscape is important for understanding their molecular contributions.
Article
Chemistry, Analytical
Emory M. Payne, Bridget E. Murray, Laura I. Penabad, Eric Abbate, Robert T. Kennedy
Summary: This article introduces a mass spectrometry-based method, mass-activated droplet sorting (MADS), for selecting cell variants grown in droplets. This method enables efficient screening and sorting of high-producing cell variants, which is of great significance for whole-cell engineering.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Ashley E. Lenhart, Robert T. Kennedy
Summary: Microfluidic devices are important for bioanalysis, but the partitioning of small molecules into PDMS can affect their accurate delivery. This study tested 11 device treatments on 21 biologically relevant small molecules and found that polybrene produced the best recovery, although recovery varied by analyte. Polybrene-treated devices enabled the detection of significant secretion changes from pancreatic islets, showing its potential for studying glucose homeostasis and diabetes.
ACS MEASUREMENT SCIENCE AU
(2023)
Article
Biochemistry & Molecular Biology
Joshua D. Jones, Monika K. Franco, Tyler J. Smith, Laura R. Snyder, Anna G. Anders, Brandon T. Ruotolo, Robert T. Kennedy, Kristin S. Koutmou
Summary: Chemical modifications to protein encoding messenger RNAs influence their localization, translation, and stability within cells. Over 15 different types of mRNA modifications have been observed by sequencing and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) approaches. LC-MS/MS is the most essential tool for studying mRNA modifications, but it has been limited by the difficulty of obtaining pure mRNA and limited sensitivities for modified nucleosides.
RSC CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Dhamyaa Abed Najm Al-Halboosi, Olena Savchenko, Lora K. Heisler, Sergiy Sylantyev
Summary: Obesity is a global health challenge caused by excessive calorie intake. The brain plays a crucial role in controlling food intake, and NAG neurons, which co-express NPY, AgRP, and GABA, are identified as hunger and food intake stimulators. Activation of 5-HT1BR leads to a decrease in food intake by suppressing NAG neuron activity and neurotransmitter release.
Article
Biochemistry & Molecular Biology
Youngsoo Kim, Lequn Geng, Ashley E. Lenhart, Jay Li, William T. Dauer, Robert T. Kennedy
Summary: Understanding the regulation of alpha-synuclein release is important for studying Parkinson's disease. The novel microdialysis method developed in this study allows for monitoring alpha-synuclein concentration in vivo.
ACS CHEMICAL NEUROSCIENCE
(2022)
