Article
Cell Biology
Yuanyuan Zhang, Xinyu Zhao, Xiaona Dong, Yuying Zhang, Haixia Zou, Yaoguang Jin, Wei Guo, Peng Zhai, Xu Chen, Alexei Kharitonenkov
Summary: Researchers have developed a GLP-1/GDF15 fusion protein and tested its potential for weight loss in animals. The molecule, QL1005, showed higher potency than the GLP-1 analog semaglutide in vitro. In obese mice, QL1005 led to reductions in body weight, food intake, insulin, fasting glucose, and triglycerides. In a cynomolgus monkey model of obesity, QL1005 dose-dependently reduced body weight, food intake, insulin, and glucose with limited side effects.
Article
Endocrinology & Metabolism
Ibiyemi Ilesanmi, George Tharakan, Kleopatra Alexiadou, Preeshila Behary, Haya Alessimii, Candace Bovill-Taylor, Julia Kenkre, Sirazum Choudhury, Chedie Doyle, Sanjay Purkayastha, Alex Miras, Christos Tsironis, Harvinder Chahal, Stephen R. Bloom, Nick S. Oliver, Ahmed R. Ahmed, Bernard Khoo, Tricia M. -M. Tan
Summary: This study showed that after RYGB surgery, patients experienced a decrease in mean glucose levels, an increase in glycemic variability, and an increase in GLP-1 response, which put them at risk for postbariatric hypoglycemia.
Article
Food Science & Technology
Fengyuan Tian, Tianxi Chen, Wangda Xu, Yichang Fan, Xiaohong Feng, Qi Huang, Jie Chen
Summary: This study suggests that curcumin may act as a natural agonist of TGR5 and an antagonist of FXR to improve obesity by promoting GLP-1 secretion through expanding L-cell population via the gut microbiota-bile acids-TGR5/FXR axis. It may serve as a promising therapeutic agent for obesity-related metabolic disorders.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Review
Endocrinology & Metabolism
Zhang-Liu Jin, Wei Liu
Summary: The global incidence of type 2 diabetes is on the rise, and bariatric surgical procedures are effective in providing relief. The mechanisms of these surgeries involve increased satiety and alterations in gastrointestinal hormones. Understanding these mechanisms can aid in developing better non-surgical treatments for type 2 diabetes.
WORLD JOURNAL OF DIABETES
(2021)
Article
Gastroenterology & Hepatology
Xin Luo, Fang Tao, Cai Tan, Chi-Ying Xu, Zhi-Hua Zheng, Qiang Pang, Xiang-An He, Jia-Qing Cao, Jin-Yuan Duan
Summary: This study aims to elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Biophysics
Luis Mauricio T. R. Lima, Luis Pena Icart
Summary: The discovery of insulin a century ago has led to a substantial increase in therapeutic polypeptides targeting diabetes and obesity. The focus is now on highly pure recombinant insulin and other peptide-based hormones and analogs. Proper formulation, storage, manipulation, and usage are required in order to avoid aggregation into high molecular weight products.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Gastroenterology & Hepatology
Florian Seyfried, Jutarop Phetcharaburanin, Maria Glymenaki, Arno Nordbeck, Mohammed Hankir, Jeremy K. Nicholson, Elaine Holmes, Julian R. Marchesi, Jia V. Li
Summary: The study investigated weight loss-independent bacterial and metabolic changes following RYGB surgery, discovering distinct metabolic and bacterial disturbances induced by the surgery. These findings provide insights into potential therapeutic targets for metabolic diseases.
Editorial Material
Endocrinology & Metabolism
Samuel Klein, Randy J. Seeley
Summary: Many individuals with obesity and type 2 diabetes experience diabetes remission after Roux-en-Y gastric bypass surgery, but there is disagreement regarding the underlying mechanisms. We present our perspective on conflicting datasets suggesting that the remission could be attributed solely to weight loss or weight loss-independent factors.
Article
Endocrinology & Metabolism
Patrick J. Knerr, Stephanie A. Mowery, Jonathan D. Douros, Bhavesh Premdjee, Karina Rahr Hjollund, Yantao He, Ann Maria Kruse Hansen, Anette K. Olsen, Diego Perez-Tilve, Richard D. DiMarchi, Brian Finan
Summary: This study aims to design unimolecular peptide triagonists that activate multiple receptors to improve metabolic diseases. The optimized triagonists show promising results in controlling body weight and enhancing energy expenditure in animal models, providing a potential new approach for obesity treatment.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Chunxia Liu, Chengye Li, Xingguang Cai, Yuxing Zou, Jiaxian Mo, Bin Chen, Yan Cai, Ting Han, Wenlong Huang, Hai Qian, Wenjie Zhang
Summary: GLP-1 receptor agonists have shown promising potential for treating metabolic diseases. Among them, CY-5 stands out for its strong hypoglycemic effect, ability to reduce weight gain, improve islet damage, and glucose tolerance, as well as its significant impact on NASH in mice.
BIOORGANIC CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
David C. D. Hope, Matthew L. Vincent, Tricia M. M. Tan
Summary: Obesity and Type 2 diabetes are global health challenges, with potential treatment options such as co-agonists showing promise in improving efficacy and reducing adverse effects. Further research is needed to guide the safe, effective, and personalized use of GLP-1/glucagon co-agonists in targeting weight loss and metabolic disease in the future.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Amanda Sheehan, Allison Goldfine, Muhammed Bajwa, Danielle Wolfs, Chisayo Kozuka, Jacqueline Piper, Kristen Fowler, Mary Elizabeth Patti
Summary: In post-bariatric hypoglycaemia patients, pramlintide does not alter glycemic or insulin responses, satiety, or dumping scores during a mixed-meal tolerance test (MMTT) and does not affect glycemic excursions or decrease low sensor glucose (SG) levels in the outpatient setting.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Patrick J. Knerr, Stephanie A. Mowery, Jonathan D. Douros, Bhavesh Premdjee, Karina Rahr Hjollund, Yantao He, Ann Maria Kruse Hansen, Anette K. Olsen, Diego Perez-Tilve, Richard D. DiMarchi, Brian Finan
Summary: This study introduces empirically optimized unimolecular peptide triagonists, which effectively reduce body weight and enhance energy expenditure in DIO mice, outperforming GLP-1R mono-agonists and GLP-1R/GIPR co-agonists. The data suggest that unimolecular poly-pharmacology is an effective means to target obesity and implicate GcgR activation as a differentiating factor in incretin receptor agonists.
MOLECULAR METABOLISM
(2022)
Review
Endocrinology & Metabolism
Jui Tu, Yangmeng Wang, Lihua Jin, Wendong Huang
Summary: Metabolic surgery, such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), is the most effective approach for treating obesity. The precise mechanisms of how these surgeries work are still unclear, but gut hormones, bile acids and gut microbiota have been identified as potential factors. The long-term goal of metabolic/bariatric surgery research is to develop new pharmacotherapeutic options for obesity and diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luis Ocana-Wilhelmi, Gracia Maria Martin-Nunez, Patricia Ruiz-Limon, Juan Alcaide, Eduardo Garcia-Fuentes, Carolina Gutierrez-Repiso, Francisco J. Tinahones, Isabel Moreno-Indias
Summary: Bariatric surgery is the most effective procedure for long-term weight loss, with gut microbiota and secondary bile acids likely playing a crucial role in the metabolic improvements seen in patients who underwent different surgical techniques.
Correction
Multidisciplinary Sciences
Paul M. Ryan, Elaine Patterson, Robert M. Kent, Helena Stack, Paula M. O'Connor, Kiera Murphy, Veronica L. Peterson, Rupasri Mandal, David S. Wishart, Timothy G. Dinan, John F. Cryan, Randy J. Seeley, Catherine Stanton, R. Paul Ross
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Gowri Nayak, Kevin X. Zhang, Shruti Vemaraju, Yoshinobu Odaka, Ethan D. Buhr, Amanda Holt-Jones, Stace Kernodle, April N. Smith, Brian A. Upton, Shane D'Souza, Jesse J. Zhan, Nicolas Diaz, Minh-Thanh Nguyen, Rajib Mukherjee, Shannon A. Gordon, Gang Wu, Robert Schmidt, Xue Mei, Nathan T. Petts, Matthew Batie, Sujata Rao, John B. Hogenesch, Takahisa Nakamura, Alison Sweeney, Randy J. Seeley, Russell N. Van Gelder, Joan Sanchez-Gurmaches, Richard A. Lang
Article
Endocrinology & Metabolism
Simon S. Evers, Ki-Suk Kim, Nadejda Bozadjieva, Alfor G. Lewis, Diana Farris, Matthew J. Sorensen, Youngsoo Kim, Steven E. Whitesall, Robert T. Kennedy, Daniel E. Michele, Randy J. Seeley, Darleen A. Sandoval
MOLECULAR METABOLISM
(2020)
Article
Cell Biology
Anthony Patrizz, Sarah J. Doran, Anjali Chauhan, Hilda Ahnstedt, Meaghan Roy-OReilly, Yun-Ju Lai, Gillian Weston, Sami Tarabishy, Anita R. Patel, Rajkumar Verma, Ilene Staff, Julia K. Kofler, Jun Li, Fudong Liu, Rodney M. Ritzel, Louise D. McCullough
Review
Cell Biology
Ruth E. Gimeno, Daniel A. Briere, Randy J. Seeley
Article
Gastroenterology & Hepatology
Andriy Myronovych, Jashdeep Bhattacharjee, Rosa-Maria Salazar-Gonzalez, Brandon Tan, Sarah Mowery, Danielle Ferguson, Karen K. Ryan, Wujuan Zhang, Xueheng Zhao, Melissa Oehrle, Kenneth D. R. Setchell, Randy J. Seeley, Darleen A. Sandoval, Rohit Kohli
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2020)
Article
Multidisciplinary Sciences
Kevin X. Zhang, Shane D'Souza, Brian A. Upton, Stace Kernodle, Shruti Vemaraju, Gowri Nayak, Kevin D. Gaitonde, Amanda L. Holt, Courtney D. Linne, April N. Smith, Nathan T. Petts, Matthew Batie, Rajib Mukherjee, Durgesh Tiwari, Ethan D. Buhr, Russell N. Van Gelder, Christina Gross, Alison Sweeney, Joan Sanchez-Gurmaches, Randy J. Seeley, Richard A. Lang
Article
Cell Biology
Nadejda Bozadjieva Kramer, Simon S. Evers, Jae Hoon Shin, Sierra Silverwood, Yibin Wang, Charles F. Burant, Darleen A. Sandoval, Randy J. Seeley
Article
Multidisciplinary Sciences
Henriette Frikke-Schmidt, Peter Arvan, Randy J. Seeley, Corentin Cras-Meneur
Summary: This study successfully tracked and quantified insulin content in up to two hundred individual islets simultaneously during a glucose challenge. The research found that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Some islets respond sharply to a glucose stimulation while others barely secrete at all.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Paul Sabatini, Henriette Frikke-Schmidt, Joe Arthurs, Desiree Gordian, Anita Patel, Alan C. Rupp, Jessica M. Adams, Jine Wang, Sebastian Beck Jorgensen, David P. Olson, Richard D. Palmiter, Martin G. Myers, Randy J. Seeley
Summary: GDF-15 activates GFRAL neurons, affecting the expression of neurotransmitters and neuropeptides, thereby inhibiting feeding and gastric emptying, promoting conditioned taste aversion; neurons with the strongest effect innervate the PBN and target CGRP(PBN) neurons, silencing of which abolishes the negative and anorectic effects of GDF-15.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Anita R. Patel, Henriette Frikke-Schmidt, Olivier Bezy, Paul Sabatini, Nikolaj Rittig, Niels Jessen, Martin G. Myers, Randy J. Seeley
Summary: The study found that Lipopolysaccharide (LPS) can increase levels of GDF15 in mice, rats, and humans, but GDF15 is not necessary for inducing anorexia and weight loss in response to moderate systemic infection.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Ki-Suk Kim, Bailey Ce Peck, Yu-Han Hung, Kieran Koch-Laskowski, Landon Wood, Priya H. Dedhia, Jason R. Spence, Randy J. Seeley, Praveen Sethupathy, Darleen A. Sandoval
Summary: This study found that vertical sleeve gastrectomy (VSG) increases the number of hormone-secreting enteroendocrine cells (EECs) in the intestine through bile acid signaling, which drives intestinal stem cell fate towards EEC differentiation.
Article
Physiology
Anita R. Patel, Henriette Frikke-Schmidt, Paul V. Sabatini, Alan C. Rupp, Darleen A. Sandoval, Martin G. Myers, Randy J. Seeley
Summary: Deoxynivalenol (DON), a mycotoxin contaminating grain, induces nausea, emesis, and anorexia. The study found that GLP-1 is not necessary for DON-induced effects on food intake and visceral illness. Additionally, the study showed that the calcium-sensing receptor (CaSR) on GFRAL neurons may play a role in DON signaling, but neither GLP-1 signaling nor GFRAL signaling and neurons are required for DON-induced visceral illness or anorexia.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2023)
Editorial Material
Endocrinology & Metabolism
Samuel Klein, Randy J. Seeley
Summary: Many individuals with obesity and type 2 diabetes experience diabetes remission after Roux-en-Y gastric bypass surgery, but there is disagreement regarding the underlying mechanisms. We present our perspective on conflicting datasets suggesting that the remission could be attributed solely to weight loss or weight loss-independent factors.
Article
Endocrinology & Metabolism
Liujun Chen, Lisha Li, Donghong Cui, Yiheng Huang, Haibin Tong, Haleh Zabihi, Shuxia Wang, Yadan Qi, Ted Lakowski, Lin Leng, Suixin Liu, Hong Wu, Lawrence H. Young, Richard Bucala, Dake Qi
Summary: Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. Cytokine macrophage migration inhibitory factor (MIF) plays a role in regulating adipose HSL and adipocyte hypertrophy. Both intracellular and extracellular MIF have opposing effects on HSL, but extracellular action predominates to downregulate HSL and exacerbate obesity development during high-fat diet (HFD).
MOLECULAR METABOLISM
(2024)
Article
Endocrinology & Metabolism
Mengyang Tang, Yi Zhang, Rong Zhang, Yuemei Zhang, Jiangfei Zheng, Daixi Wang, Xinyu Wang, Jing Yan, Cheng Hu
Summary: This study aimed to explore the role of GPSM1 in POMC neurons and the underlying mechanisms in metabolic homeostasis. Through various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies, the study revealed the pathophysiological role of GPSM1 in POMC neurons and its regulation of POMC neuron activity.
MOLECULAR METABOLISM
(2024)