Review
Endocrinology & Metabolism
Sara Amjad, Sabah Nisar, Ajaz A. Bhat, Ab Rauf Shah, Michael P. Frenneaux, Khalid Fakhro, Mohammad Haris, Ravinder Reddy, Zoltan Patay, Joseph Baur, Puneet Bagga
Summary: NAD(+) plays a critical role in cellular bioenergetics and its depletion is associated with various diseases, making boosting NAD(+) levels a potential therapeutic strategy. However, the specific mechanisms of NAD(+) action require further investigation.
MOLECULAR METABOLISM
(2021)
Article
Immunology
Amin Izadpanah, Joseph C. Mudd, Joe G. N. Garcia, Sudesh Srivastav, Mohamed Abdel-Mohsen, Clovis Palmer, Aaron R. Goldman, Jay K. Kolls, Xuebin Qin, Jay Rappaport
Summary: Severe COVID-19 infection can lead to persistent symptoms such as pulmonary dysfunction, fatigue, and neurocognitive abnormalities. Dysregulated NAD metabolism may contribute to these abnormalities. By studying transgenic mice and sequencing data from SARS-CoV-2 infected patients, it was found that NAD biosynthetic enzymes and consuming enzymes are dysregulated in the infection. Modulating NAD pathways with nicotinamide riboside (NR) and anti-NAMPT antibody may offer therapeutic benefits for SARS-CoV-2 infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Zhuming Fan, Zhiyang Liu, Nan Zhang, Wenyu Wei, Ke Cheng, Hongyan Sun, Quan Hao
Summary: Lysine lactylation (Kla) is a newly discovered histone post-translational modification. HDAC1-3 have been identified as effective Kla erasers. SIRT3 shows higher eraser activity against H4K16la site and its binding mechanisms have been revealed. Chemical probes have been developed to capture potential Kla erasers and detect Kla for further research on its roles in gene transcription regulation.
Article
Cell Biology
Oyvind Stromland, Joseph Diab, Eugenio Ferrario, Lars J. Sverkeli, Mathias Ziegler
Summary: NAD(+) is an important coenzyme in redox reactions and cellular signaling, regulating essential processes like DNA repair, immune cell function, senescence, and chromatin remodeling. The decline of NAD(+) levels with age has been linked to various age-related diseases such as metabolic diseases and cognitive decline. Therapeutic augmentation of NAD(+) levels can halt or reverse the progression of age-related diseases.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
Review
Nutrition & Dietetics
Ekaterina Podyacheva, Yana Toropova
Summary: Despite the progress in developing new anticancer strategies, the issue of doxorubicin cardiotoxicity remains unresolved. Nicotinamide riboside, a precursor to NAD(+), shows potential in addressing this problem, although there is limited research on its effects on cardiomyopathy.
Article
Oncology
Sanxing Guo, Fengying Li, Yixuan Liang, Yufei Zheng, Yingyi Mo, Deyao Zhao, Zhixiong Jiang, Mengmeng Cui, Lixia Qi, Jiaxing Chen, Lixin Wan, Guoyong Chen, Sidong Wei, Qi Yang, Junqi Liu
Summary: AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, suggesting it as a potential target for HCC treatment.
Review
Cell Biology
Mohammed Hamed Alqarni, Ahmed Ibrahim Foudah, Magdy Mohamed Muharram, Nikolaos E. Labrou
Summary: Sirtuins (SIRTs) are a family of histone deacetylases that play complex roles in cell physiology, with recent studies highlighting SIRT1 and SIRT2 as promising antiviral targets. Natural polyphenol-based SIRT modulators show potential in controlling SIRT's functional roles in various diseases, including viral infections.
Review
Cell Biology
Daniel C. Levine, Kathryn M. Ramsey, Joseph Bass
Summary: Intrinsic circadian clocks regulate daily anticipation of light/dark cycles and energy storage/utilization cycles. Disruption of the core clock can contribute to disease. Peripheral clocks can be influenced by metabolic cues. NAD(P)(H) nucleotides and NAD+-dependent sirtuin deacetylases play a key role in integrating circadian and metabolic cycles.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tao Wang, Fei Zhang, Wuxun Peng, Lei Wang, Jian Zhang, Wentao Dong, Xiaobin Tian, Chuan Ye, Yanlin Li, Yuekun Gong
Summary: This study confirms that overexpressing NMNAT3 can improve mitochondrial function and resistance to stress-induced apoptosis in BMSCs. By increasing NAD+ levels, NMNAT3 can increase the activity of Sirt3 and decrease the acetylation levels of related proteins. This provides a new mechanism and approach for improving the survival rate and curative effect of BMSCs.
BIOSCIENCE REPORTS
(2022)
Article
Fisheries
Yanlin Guo, Dong Huang, Feiyang Chen, Shuoli Ma, Wanyou Zhou, Wenbing Zhang, Kangsen Mai
Summary: The deposition of lipids in abalone is influenced by dietary lipid levels through the regulation of AMPK alpha 2/PPAR alpha and JNK/mTOR/SREBP-1c pathways. Higher and lower dietary lipid levels both have different effects on the expression of genes involved in fatty acid transport, lipolysis, and de-novo lipogenesis in the hepatopancreas and muscle of abalone.
Article
Multidisciplinary Sciences
Kaili Ma, Lina Sun, Mingjing Shen, Xin Zhang, Zhen Xiao, Jiajia Wang, Xiaowei Liu, Kanqiu Jiang, F. Xiao-Feng Qin, Feng Guo, Baojun Zhang, Lianjun Zhang
Summary: NAD(+) degradation and CD38 play a role in regulating the antitumor immunity of CD8(+) T cells. Partially reversing T cell dysfunction, Cd38 deficiency does not affect the exhausted differentiation of CD8(+) T cells in tumors. Decreased NAD(+) is correlated with T cell dysfunction, but deficiency of CD38 alone is not enough to rescue NAD(+) in tumor infiltrated CD8(+) T cells.
Article
Biochemistry & Molecular Biology
Krish Chandrasekaran, Neda Najimi, Avinash R. Sagi, Sushuma Yarlagadda, Mohammad Salimian, Muhammed Ikbal Arvas, Ahmad F. Hedayat, Yanni Kevas, Anand Kadakia, James W. Russell
Summary: Administration of NAD(+) precursors, NMN or NR, can prevent diabetic peripheral neuropathy, improve sensory function, and prevent nerve fiber loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Mehrshad Sadria, Anita T. Layton
Summary: Cells adapt their metabolism and activities in response to signals from their surroundings, and proteins like mTOR, AMPK, and sirtuins play essential roles in regulating metabolic stress and energy balance. The computational model developed in this study sheds light on complex interactions among signaling pathways, offering insights for novel treatment approaches in diseases such as cancer.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Cell Biology
Yongyuan He, Yinghong Su, Chengcheng Duan, Siyuan Wang, Wei He, Yingting Zhang, Xiaofei An, Ming He
Summary: With the global aging population, nonalcoholic fatty liver disease (NAFLD) has dramatically increased in recent decades. It is a progressive disease that ranges from simple fatty liver to liver cirrhosis and hepatocellular carcinoma (HCC). Aging plays a crucial role in the development and progression of NAFLD, HCC, and other age-related liver diseases. The involvement of senescent cells and aging-related factors, such as NAD+, sirtuins, and mTOR, in the development of NAFLD has been explored, although their significance remains underestimated. This review summarizes current research on the roles of aging, cellular senescence, and aging-related factors in the evolution of NAFLD to HCC, with the aim of identifying potential therapeutic targets for aging-related NAFLD and its progression.
AGEING RESEARCH REVIEWS
(2023)
Article
Cell Biology
Elma Zaganjor, Haejin Yoon, Jessica B. Spinelli, Elizabeth R. Nunn, Gaelle Laurent, Paulina Keskinidis, Suganja Sivaloganathan, Shakchhi Joshi, Giulia Notarangelo, Stacy Mulei, Mathew T. Chvasta, Sarah A. Tucker, Krystle Kalafut, Robert A. H. van de Ven, Clary B. Clish, Marcia C. Haigis
Summary: This study provides a temporal analysis of adipocyte differentiation, uncovering early metabolic events that stimulate transcriptional reprogramming.
Article
Endocrinology & Metabolism
Morten Lyng Hogild, Astrid Johannesson Hjelholt, Jakob Hansen, Steen Bonlokke Pedersen, Niels Moller, Jorgen F. P. Wojtaszewski, Mogens Johannsen, Niels Jessen, Jens Otto Lunde Jorgensen
Summary: This study reveals that administration of β-OHB can increase insulin sensitivity by suppressing lipolysis.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Geriatrics & Gerontology
Amy Zheng, Seong Eun Kwak, Jesper B. Birk, Edward B. Arias, Dominic Thorley, Jorgen F. P. Wojtaszewski, Gregory D. Cartee
Summary: This study investigated the impact of caloric restriction (CR) on AMP-activated protein kinase (AMPK) and its substrates in skeletal muscle of older animals. The results revealed that CR significantly increased the phosphorylation of AMPK and several AMPK substrates, suggesting a potential role of AMPK in the antiaging effects of CR.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Oncology
Joan M. M. Marmol, Michala Carlsson, Steffen H. H. Raun, Mia K. K. Grand, Jonas Sorensen, Louise Lang Lehrskov, Erik A. A. Richter, Ole Norgaard, Lykke Sylow
Summary: Background: Insulin resistance is common in cancer patients and is associated with higher recurrence rates and reduced survival. However, it is unclear how frequently this condition occurs in patients with cancer. Methods: A systematic review and meta-analysis were conducted to assess insulin resistance in cancer patients. Fifteen studies were included, showing that cancer patients have significantly lower insulin-stimulated glucose disposal rates compared to control subjects. Interpretation: These findings highlight the importance of addressing insulin resistance in cancer patients to improve outcomes and patient care.
Article
Endocrinology & Metabolism
Rasmus Kjobsted, Jonas M. Kristensen, Nicolas O. Eskesen, Kohei Kido, Klara Fjorder, Ditte F. Damgaard, Jeppe K. Larsen, Nicoline R. Andersen, Jesper B. Birk, Anders Gudiksen, Jonas T. Treebak, Peter Schjerling, Henriette Pilegaard, Jrgen F. P. Wojtaszewski
Summary: The ability of insulin to stimulate glucose uptake in skeletal muscle is essential for controlling blood sugar levels in the body. Research shows that the phosphorylation of TBC1D4 by AMPK is the main mechanism behind the improved glucose uptake after exercise. A mouse model was created to investigate this mechanism further, and the results revealed that TBC1D4-S711 plays a crucial role in mediating the insulin-sensitizing effect of exercise on muscle glucose uptake.
Article
Endocrinology & Metabolism
Josephine M. Kanta, Luisa Deisen, Kornelia Johann, Stephanie Holm, Annemarie Lundsgaard, Jens Lund, Markus Jaehnert, Annette Schuermann, Christoffer Clemmensen, Bente Kiens, Andreas M. Fritzen, Maximilian Kleinert
Summary: This study found that medium chain fatty acids (MCFAs) can reduce food intake in rodents and humans, but the underlying mechanisms are unknown. It was discovered that MCFAs trigger the release of hepatic factors that reduce appetite. MCFAs intake increases circulating GDF15 levels and requires the GDF15-GFRAL axis for its anorectic effect.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Tummas Ternhamar, Andreas Moller, Christoffer Martinussen, Maria S. Svane, Morten Hindso, Nils B. Jorgensen, Carsten Dirksen, Jens-Erik Beck Jensen, Bolette Hartmann, Jens J. Holst, Bente Kiens, Sten Madsbad, Kirstine N. Bojsen-Moller
Summary: Moderate intensity cycling shortly after meal intake does not increase the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery. A low glycemic index meal increases nadir glucose and reduces glucose excursions compared with a high glycemic index meal. Participants who underwent Roux-en-Y gastric bypass surgery had lower postexercise glucagon responses compared with controls.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Cell Biology
Kim A. Sjoberg, Casper M. Sigvardsen, Abdiel Alvarado-Diaz, Nicoline Resen Andersen, Mark Larance, Randy J. Seeley, Peter Schjerling, Jakob G. Knudsen, Georgios Katzilieris-Petras, Christoffer Clemmensen, Sebastian Beck Jorgensen, Katrien De Bock, Erik A. Richter
Summary: Growth differentiation factor 15 (GDF15) improves insulin action in obese rodents without weight loss by enhancing suppression of glucose production and increasing glucose uptake in adipose tissue and liver. This effect is mediated by GFRAL receptor and 0-adrenergic signaling. GDF15 also reduces glucagon levels independently of the GFRAL receptor.
Article
Physiology
Ed Maunder, Jeffrey A. Rothschild, Andreas M. Fritzen, Andreas B. Jordy, Bente Kiens, Matthew J. Brick, Warren B. Leigh, Wee-Leong Chang, Andrew E. Kilding
Summary: The study aimed to assess the variation in fatty acid oxidation rates during exercise explained by skeletal muscle proteins involved in fatty acid transport. The results showed associations between FATP1, FATP4, CD36, and FABPpm with fatty acid oxidation rates. These findings suggest the importance of skeletal muscle proteins involved in fatty acid transport in regulating fatty acid oxidation rates during exercise.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lisbeth L. V. Moller, Mona S. Ali, Jonathan Davey, Steffen H. Raun, Nicoline R. Andersen, Jonathan Z. Long, Hongwei Qian, Jacob F. Jeppesen, Carlos Henriquez- Olguin, Emma Frank, Thomas E. Jensen, Kurt Hojlund, Jorgen F. P. Wojtaszewski, Joachim Nielsen, Tim T. Chiu, Mark P. Jedrychowski, Paul Gregorevic, Amira Klip, Erik A. Richter, Lykke Sylow
Summary: RhoGDIα is identified as a key regulator in controlling skeletal muscle insulin sensitivity by interacting with Rac1 and modulating GLUT4 translocation. Overexpression of RhoGDIα impairs insulin action and glucose tolerance, and elevated RhoGDIα protein content is observed in skeletal muscles of insulin-resistant patients with type 2 diabetes. This study highlights the clinical relevance of RhoGDIα as a controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
T. C. Phung Pham, Lucile Dollet, Mona S. Ali, Steffen H. Raun, Lisbeth L. V. Moller, Abbas Jafari, Nicholas Ditzel, Nicoline R. Andersen, Andreas M. Fritzen, Zachary Gerhart-Hines, Bente Kiens, Anu Suomalainen, Stephen J. Simpson, Morten Salling Olsen, Arnd Kieser, Peter Schjerling, Anni I. Nieminen, Erik A. Richter, Essi Havula, Lykke Sylow
Summary: Studies have found that the TNIK gene plays an important role in regulating lipid and glucose homeostasis in fruit flies and mice. Loss of the TNIK gene in fruit flies and mice resulted in changes in metabolite profiles and impaired lipogenesis. Additionally, TNIK gene variants were found to be associated with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior.
