Article
Biochemistry & Molecular Biology
Ruta Dekeryte, Zara Franklin, Claire Hull, Lorenzo Croce, Sarah Kamli-Salino, Oliver Helk, Philip A. Hoffmann, Zhixiang Yang, Gernot Riedel, Mirela Delibegovic, Bettina Platt
Summary: The study demonstrates the role of BACE1 in regulating systemic glucose homeostasis and suggests BACE1 inhibitors for treating T2DM-associated pathologies. LY2886721 treatment improved glucose homeostasis and hepatic insulin sensitivity in PLB4 mice, but did not show improvements in motor coordination.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Maria Luengo-Mateos, Antia Gonzalez-Vila, Nathalia Romanelli Vicente Dragano, Nataliia Ohinska, Maria Silveira-Loureiro, Marco Gonzalez-Dominguez, Anxela Estevez-Salguero, Paula Novelle-Rodriguez, Miguel Lopez, Olga Barca-Mayo
Summary: Here, we show that hypothalamic astrocytic BMAL1 plays a role in computing cyclic metabolic information for optimizing energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Furthermore, female mice with BMAL1 knockdown in astrocytes exhibit a male-like metabolic obese phenotype when fed a high-fat diet. These findings highlight the importance of astrocytic BMAL1 in the regulation of energy homeostasis and its potential implications in the physiopathology of obesity and related comorbidities.
Article
Cell Biology
Barbara Bettegazzi, Laura Sebastian Monasor, Serena Bellani, Franca Codazzi, Lisa Michelle Restelli, Alessio Vittorio Colombo, Nikolaus Deigendesch, Stephan Frank, Takashi Saito, Takaomi C. Saido, Sven Lammich, Sabina Tahirovic, Fabio Grohovaz, Daniele Zacchetti
Summary: The study provides evidence for the role of Casein Kinase 2 in controlling BACE1 expression and demonstrates a mechanism linking neuronal activity with amyloid production and deposition in the brain. The findings offer new perspectives for AD treatment strategies.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Dan Chen, Yong Qi, Jia Zhang, Yunlei Yang
Summary: This study reveals the role of astrocytes in regulating adipose sympathetic nerve activity and adipocyte functions, showing that astrocyte stimulation can increase sympathetic activity and promote lipolysis. Additionally, the study found that astrocyte stimulation excites POMC neurons in the arcuate nucleus, which could be a potential target for obesity treatment.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Byong Seo Park, Dasol Kang, Kwang Kon Kim, Bora Jeong, Tae Hwan Lee, Jeong Woo Park, Shioko Kimura, Jung -Yong Yeh, Gu Seob Roh, Chang-Joong Lee, Sungchil Yang, Sunggu Yang, Jae Geun Kim, Byung Ju Lee
Summary: The study reveals that hypothalamic TTF-1 plays a crucial role in leptin signaling and activity, with its selective deletion enhancing the effects of leptin and alleviating obesity caused by leptin resistance. This suggests that TTF-1 may be a potential therapeutic target for the treatment of obesity.
MOLECULAR METABOLISM
(2022)
Article
Cell Biology
Marek Adamowski, Karolina Wolodko, Joana Oliveira, Juan Castillo-Fernandez, Daniel Murta, Gavin Kelsey, Antonio M. Galvao
Summary: The study characterized the activation levels of NLRP3 inflammasome in the ovaries and liver of mice during obesity progression, revealing a link between leptin signaling and NLRP3 inflammasome activation in the ovary throughout obesity progression. Both ovaries and liver showed differential expression of NLRP3 and IL-1 beta proteins in various experimental models, shedding light on the molecular mechanisms underlying ovarian failure in maternal obesity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Krista Mineia Wartchow, Leticia Rodrigues, Izabela Swierzy, Michael Buchfelder, Diogo Onofre de Souza, Carlos-Alberto Goncalves, Andrea Kleindienst
Summary: The study found that long-term increased S100B levels have sex-dependent and brain region-specific effects on amyloid-beta processing, highlighting the importance of further investigating signaling pathways and behavioral responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Xiao Lv, Feng Gao, Tuo Peter Li, Peng Xue, Xiao Wang, Mei Wan, Bo Hu, Hao Chen, Amit Jain, Zengwu Shao, Xu Cao
Summary: In this study, it was found that ascending skeleton interoceptive signaling downregulates hypothalamic NPY expression, inducing lipolysis and promoting osteoblastic bone formation. SMILE plays a key role in this process by inhibiting NPY expression. Inhibition of NPY Y1 receptor can rescue bone loss.
Article
Multidisciplinary Sciences
Seul Ki Kim, Le Trung Tran, Cherl NamKoong, Hyung Jin Choi, Hye Jin Chun, Yong-ho Lee, MyungHyun Cheon, ChiHye Chung, Junmo Hwang, Hyun-Ho Lim, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: The mitochondrial-derived peptide SHLP2 plays a crucial role in energy homeostasis by activating hypothalamic neurons and binding to CXCR7. It protects against obesity and improves insulin sensitivity in mice fed a high-fat diet.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Seul Ki Kim, Le Trung Tran, Cherl NamKoong, Hyung Jin Choi, Hye Jin Chun, Yong-ho Lee, MyungHyun Cheon, ChiHye Chung, Junmo Hwang, Hyun-Ho Lim, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: Small humanin-like peptide 2 (SHLP2), a mitochondrial-derived peptide, plays a crucial role in energy homeostasis. The study demonstrates that SHLP2 can protect mice from high-fat diet-induced obesity and improve insulin sensitivity. It activates pro-opiomelanocortin (POMC) neurons in the hypothalamus, which suppresses food intake and promotes thermogenesis. The researchers also discover that SHLP2 binds to and activates chemokine receptor 7 (CXCR7).
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Seul Ki Kim, Le Trung Tran, Cherl NamKoong, Hyung Jin Choi, Hye Jin Chun, Yong-ho Lee, MyungHyun Cheon, ChiHye Chung, Junmo Hwang, Hyun-Ho Lim, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Summary: Small humanin-like peptide 2 (SHLP2), a mitochondrial-derived peptide, plays an important role in energy homeostasis. In this study, the authors demonstrate that SHLP2 protects male mice from high-fat diet-induced obesity and improves insulin sensitivity. The activation of hypothalamic neurons and the binding of SHLP2 to CXCR7 are involved in the regulation of food intake, energy expenditure, and glucose homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Leilei Yang, Peng Lu, Xiangyu Qi, Qian Yang, Luna Liu, Tao Dou, Qingbo Guan, Chunxiao Yu
Summary: The study shows that metformin treatment improves insulin sensitivity, reduces blood glucose and lipid levels, and alleviates hypothalamic aging in obese mice. Additionally, metformin reduces the expression of endoplasmic reticulum stress-related proteins and decreases the inflammatory response triggered by microglia activation.
Article
Biochemistry & Molecular Biology
Lige Leng, Ziqi Yuan, Xiao Su, Zhenlei Chen, Shangchen Yang, Meiqin Chen, Kai Zhuang, Hui Lin, Hao Sun, Huifang Li, Maoqiang Xue, Jun Xu, Jingqi Yan, Zhenyi Chen, Tifei Yuan, Jie Zhang
Summary: Aging is a systemic process that poses a risk to physiological functions and eventual death. The molecular mechanisms underlying aging and cognitive decline are not fully understood. Recent findings show that Menin plays a role in neuroinflammation and brain development. In aged mice, there is a decrease in Menin signaling in the hypothalamus, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in the ventromedial nucleus of the hypothalamus in aged mice improves lifespan, learning and memory, and aging biomarkers, while inhibiting Menin in middle-aged mice accelerates aging and cognitive decline. Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism, and the reduction of Menin in aging leads to impaired D-serine release in the VMH-hippocampus neural circuit. Supplementation of D-serine rescues cognitive decline in aged mice. In conclusion, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.
Article
Biochemistry & Molecular Biology
Lanlan Jia, Zhengli Chen, Ting Pan, Yu Xia, Junbo He, Asad Jahangir, Xiaoli Wei, Wentao Liu, Riyi Shi, Chao Huang, Qihui Luo
Summary: The study shows that TRIM67 in the hypothalamus responds to body-energy homeostasis and a deficiency of TRIM67 exacerbates metabolic disorders in obese mice induced by high-fat diet. Neuroinflammation and apoptosis were found in the hypothalamus of obese TRIM67 KO mice. Reduced BDNF in the hypothalamus affects sympathetic nervous system innervation and contributes to lipid accumulation under high-fat diet exposure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Endocrinology & Metabolism
Hannah Chatwin, Melanie Broadley, Christel Hendrieckx, Jill Carlton, Simon Heller, Stephanie A. Amiel, Bastiaan de Galan, Rory J. McCrimmon, Ulrik Pedersen-Bjergaard, Frans Pouwer, Jane Speight
Summary: Hypoglycemia has a negative impact on various domains of quality of life for adults with type 1 diabetes, including leisure activities, physical health, ability to keep fit and be active, sleep, emotional well-being, spontaneity, independence, work/studies, and dietary freedom. Psychological factors play a larger role in explaining this negative impact than hypoglycemia frequency and awareness.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2023)
Article
Endocrinology & Metabolism
Rory J. McCrimmon, Alice Y. Y. Cheng, Gagik Galstyan, Khier Djaballah, Xuan Li, Mathieu Coudert, Juan P. Frias
Summary: This study compared the clinical effectiveness of iGlarLixi and BI + RAI regimens in patients with type 2 diabetes. The results showed that in real-world clinical practice, the two regimens had similar glycemic control, but iGlarLixi led to less weight gain.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Philip D. Home, Rory J. McCrimmon, Julio Rosenstock, Matthias Bluher, Katrin Pegelow, Lydie Melas-Melt, Khier Djaballah, Francesco Giorgino
Summary: The aim of this study was to investigate the impact of baseline participant characteristics on the outcomes of the SoliMix study. The findings showed that the treatment effects of iGlarLixi were consistent across various baseline characteristics, supporting its use as an effective and well-tolerated treatment option for people with type 2 diabetes.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Jill Carlton, Philip Powell, Donna Rowen, Melanie Broadley, Frans Pouwer, Jane Speight, Simon Heller, Mari-Anne Gall, Myriam Rosilio, Christopher J. Child, Jonathan Comins, Rory J. McCrimmon, Bastiaan de Galan, John Brazier
Summary: This study aims to develop a new hypoglycaemia-specific PROM to assess the impact of hypoglycaemia on quality of life in patients with diabetes. The study uses a mixed-methods, three-stage design, collecting information through qualitative interviews and validating it through psychometric testing, ultimately generating a hypoglycaemia-specific PROM and preference-based measure.
Article
Endocrinology & Metabolism
Huan Wang, Ruth L. M. Cordiner, Yu Huang, Louise Donnelly, Simona Hapca, Andrew Collier, John J. McKnight, Brian R. Kennon, Fraser R. Gibb, Paul McKeigue, Sarah Wild, Helen Colhoun, John Chalmers, John Petrie, Naveed Sattar, Thomas MacDonald, Rory McCrimmon, Daniel Morales, Ewan Pearson
Summary: This study developed a robust methodology for causal inference and assessed the real-world cardiovascular safety of sulfonylureas compared to dipeptidyl peptidase 4 inhibitors and thiazolidinediones. The findings suggest that second-line sulfonylureas are unlikely to increase cardiovascular risk or all-cause mortality.
Article
Endocrinology & Metabolism
Alison R. McNeilly, Jennifer L. Gallagher, Mark E. Evans, Bastiaan de Galan, Ulrik Pedersen-Bjergaard, Bernard T. Thorens, Albena Dinkova-Kostova, Jeffrey-T. Huang, Michael L. J. J. Ashford, Rory McCrimmon
Summary: Chronic hyperglycaemia and recurrent hypoglycaemia are independently associated with accelerated cognitive decline in type 1 diabetes. This study examines the hypothesis that post-hypoglycaemic hyperglycaemia exacerbates hippocampal oxidative stress and explores potential contributory mechanisms.
Editorial Material
Medicine, General & Internal
Rory J. Mccrimmon
Article
Multidisciplinary Sciences
Uffe Soholm, Melanie Broadley, Natalie Zaremba, Patrick Divilly, Giesje Nefs, Jill K. Carlton, Julia Mader, Petra Martina Baumann, Mikel Gomes, Gilberte J. Martine-Edith, Daniel Pollard, Dajana Rath, Simon Heller, Ulrik J. Pedersen-Bjergaard, Rory McCrimmon, Eric Renard, Mark Evans, Bastiaan de Galan, Thomas A. Forkmann, Stephanie Amiel, Christel Hendrieckx, Jane Speight, Pratik Choudhary, Frans Pouwer
Summary: The aim of this study was to determine the acceptability and psychometric properties of the Hypo-METRICS app, which is designed to assess the impact of hypoglycemia on daily functioning in people with insulin-treated diabetes. Participants completed daily check-ins for 10 weeks using the app and answered questions about their subjective daily functioning. The results showed high completion rates, satisfactory psychometric properties, and demonstrated that the app is acceptable and reliable for exploring the daily impact of hypoglycemia.
Article
Endocrinology & Metabolism
Clementine E. M. Verhulst, Julia I. P. W. van Heck, Therese Fabricius, Rinke Stienstra, Steven J. Teerenstra, Rory J. McCrimmon, Cees Tack, Ulrik E. Pedersen-Bjergaard, Bastiaan de Galan, Hypo RESOLVE Consortium
Summary: The aim of this study was to determine the duration and extent of the inflammatory response to hypoglycemia in individuals with type 1 diabetes and healthy controls. The results showed that hypoglycemia increased the counts of lymphocytes and monocytes, which remained elevated for one week. In addition, hypoglycemia also led to an increase in the release of pro-inflammatory cytokines and an elevation of circulating inflammatory proteins, both of which lasted for at least one week.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Nicola Morrice, Susanne Vainio, Kirsi Mikkola, Lidy van Aalten, Jennifer R. Gallagher, Michael L. J. Ashford, Alison D. McNeilly, Rory J. McCrimmon, Alexandra Grosfeld, Patricia Serradas, Jukka Koffert, Ewan R. Pearson, Pirjo Nuutila, Calum Sutherland
Summary: This study aims to investigate the impact of the glucose transporter SLC2A2 on the response to metformin treatment, and reveals the differential response to metformin depending on SLC2A2 expression. It also provides evidence that metformin can modify glucose transport in the gut, contributing to its efficacy. Additionally, this study identifies an important role for this transporter in maintaining efficient glucose homoeostasis during aging.
MOLECULAR METABOLISM
(2023)
Article
Clinical Neurology
Sarmi Sri, Adam Greenstein, Alessandra Granata, Alex Collcutt, Angela C. C. Jochems, Barry W. McColl, Blanca Diaz Castro, Caleb Webber, Carmen Arteaga Reyes, Catherine Hall, Catherine B. Lawrence, Cheryl Hawkes, Chrysia-Maria Pegasiou-Davies, Claire Gibson, Colin L. Crawford, Colin Smith, Denis Vivien, Fiona H. McLean, Frances Wiseman, Gaia Brezzo, Giovanna Lalli, Harry A. T. Pritchard, Hugh S. Markus, Isabel Bravo-Ferrer, Jade Taylor, James Leiper, Jason Berwick, Jian Gan, John Gallacher, Jonathan Moss, Jozien Goense, Letitia McMullan, Lorraine Work, Lowri Evans, Michael S. Stringer, M. L. J. Ashford, Mohamed Abulfadl, Nina Conlon, Paresh Malhotra, Philip Bath, Rebecca Canter, Rosalind Brown, Selvi Ince, Silvia Anderle, Simon Young, Sophie Quick, Stefan Szymkowiak, Steve Hill, Stuart Allan, Tao Wang, Terry Quinn, Tessa Procter, Tracy Farr, Xiangjun Zhao, Zhiyuan Yang, Atticus H. Hainsworth, Joanna M. Wardlaw
Summary: Although Alzheimer's disease has dominated dementia research, it is now recognized that most dementia in older people is caused by a combination of vascular and Alzheimer's brain pathology. This review provides a perspective on the limitations of current vascular cognitive impairment (VCI) models and offers recommendations for improving translation and reproducibility. The authors discuss reproducibility, clinical features of VCI, human pathology, bioinformatics approaches, and data sharing, and emphasize the importance of small vessel disease in future research.
CEREBRAL CIRCULATION-COGNITION AND BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Lia M. Pinto, Alexandros Pailas, Max Bondarchenko, Abhishek Bharadwaj Sharma, Katrin Neumann, Anthony J. Rizzo, Celine Jeanty, Nathalie Nicot, Carine Racca, Mindy K. Graham, Catherine Naughton, Yaqun Liu, Chun-Long Chen, Paul J. Meakin, Nick Gilbert, Sebastien Britton, Alan K. Meeker, Christopher M. Heaphy, Florence Larminat, Eric Van Dyck
Summary: Maintaining chromatin integrity at centromeres is crucial for preventing DNA breaks and genomic instability. The histone chaperone complex ATRX/DAXX is involved in establishing and maintaining centromeric chromatin structure. We discovered a novel ATRX-independent function for DAXX in promoting genome stability by preventing R-loop accumulation and DNA double-strand break formation at centromeres.
NUCLEIC ACIDS RESEARCH
(2023)