Article
Medicine, Research & Experimental
Mohammad Irshad Reza, Anees A. Syed, Pragati Singh, Athar Husain, Jiaur R. Gayen
Summary: Mitochondrial dysfunction induced by PST is responsible for hepatic steatosis in T2D, and protection from these abnormalities can be achieved by knockdown of Chga gene or administration of PST inhibitor.
Article
Gastroenterology & Hepatology
Hong Fan, Zhenqiu Liu, Pengyan Zhang, Sheng Wu, Xinyu Han, Yiwen Huang, Yichen Zhu, Xingdong Chen, Tiejun Zhang
Summary: Non-MAFLD steatosis has similar clinical and genetic features to MAFLD steatosis, and it increases the risk of mortality.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Ritesh K. Baboota, Aidin Rawshani, Laurianne Bonnet, Xiangyu Li, Hong Yang, Adil Mardinoglu, Tamar Tchkonia, James L. Kirkland, Anne Hoffmann, Arne Dietrich, Jeremie Boucher, Matthias Bluher, Ulf Smith
Summary: Hepatic cell senescence is a key factor in human NAFLD/NASH. BMP4 and Gremlin 1 are identified as novel therapeutic targets.
Article
Gastroenterology & Hepatology
Lili Cheng, R. N. V. Krishna Deepak, Guoqiang Wang, Ziyi Meng, Lei Tao, Mengqing Xie, Wenna Chi, Yuming Zhang, Mingming Yang, Yilie Liao, Ruiqun Chen, Yu Liang, Junyu Zhang, Yuedong Huang, Weihua Wang, Zhiying Guo, Yunfang Wang, Jiandie D. Lin, Hao Fan, Ligong Chen
Summary: SLC25A47 plays an important role in hepatic metabolism by regulating lipid homeostasis through the phosphorylation of AMP-activated protein kinase a (AMPK alpha). Deficiency of SLC25A47 is associated with increased hepatic lipid content, triglycerides, and cholesterol levels, and promotes HCC tumorigenesis and development. SLC25A47 is also identified as one of the pharmacological targets of metformin.
Article
Cell Biology
Panu K. Luukkonen, Kimmo Porthan, Noora Ahlholm, Fredrik Rosqvist, Sylvie Dufour, Xian-Man Zhang, Tiina E. Lehtimaki, Wenla Seppanen, Marju Orho-Melander, Leanne Hodson, Kitt Falk Petersen, Gerald I. Shulman, Hannele Yki-Jarvinen
Summary: The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but its underlying pathophysiology is still unclear. This study used state-of-the-art stable isotope techniques to investigate the effect of this variant on hepatic metabolism. The findings show that homozygous carriers of the PNPLA3 I148M variant have altered hepatic mitochondrial function, leading to reduced de novo lipogenesis and increased ketogenesis.
Article
Endocrinology & Metabolism
Sofiya Gancheva, Sabine Kahl, Dominik Pesta, Lucia Mastrototaro, Bedair Dewidar, Klaus Strassburger, Ehsan Sabah, Irene Esposito, Jurgen Weiss, Theresia Sarabhai, Martin Wolkersdorfer, Thomas Fleming, Peter Nawroth, Marcel Zimmermann, Andreas S. Reichert, Matthias Schlensak, Michael Roden
Summary: Individuals with type 2 diabetes have a higher risk of progressing from nonalcoholic fatty liver to steatohepatitis, fibrosis, and cirrhosis. The hepatic mitochondrial function in NASH patients with and without type 2 diabetes differs, impacting disease progression.
Article
Endocrinology & Metabolism
Sofiya Gancheva, Sabine Kahl, Dominik Pesta, Lucia Mastrototaro, Bedair Dewidar, Klaus Strassburger, Ehsan Sabah, Irene Esposito, Juergen Weiss, Theresia Sarabhai, Martin Wolkersdorfer, Thomas Fleming, Peter Nawroth, Marcel Zimmermann, Andreas S. Reichert, Matthias Schlensak, Michael Roden
Summary: Loss of hepatic mitochondrial adaptation characterizes NASH and type 2 diabetes or hepatic fibrosis and may thereby favor accelerated disease progression.
Review
Biochemistry & Molecular Biology
Georgiana-Diana Cazac, Cristina-Mihaela Lacatusu, Gabriela Stefanescu, Catalina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
Summary: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, especially among patients with type 2 diabetes mellitus (T2DM). Currently, there are no approved pharmacologic therapies for NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are being evaluated as potential candidates for NAFLD treatment in T2DM patients. Some GLP-1RAs have shown potential benefits in reducing hepatic steatosis, improving nonalcoholic steatohepatitis (NASH) lesions, and slowing down fibrosis progression in NAFLD patients.
Article
Gastroenterology & Hepatology
Yeeun Choi, Min-Ji Song, Woong-Jae Jung, Haengdueng Jeong, Seokjae Park, Bobae Yang, Eun-Chong Lee, Jung-Sik Joo, Dahee Choi, Seung-Hoi Koo, Eun-Kyoung Kim, Ki Taek Nam, Hyoung-Pyo Kim
Summary: This study demonstrated that liver-specific deletion of CTCF leads to hepatic steatosis and inflammation in mice, which is associated with increased nuclear accumulation of PPAR gamma and upregulation of downstream target genes such as CD36. Repression of PPAR gamma through pharmacologic blockade or adenovirus-mediated knockdown could ameliorate hepatic steatosis in CTCF-deficient mice.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qi Han, Huiling Chen, Likai Wang, Yang An, Xiaoxiang Hu, Yaofeng Zhao, Hao Zhang, Ran Zhang
Summary: Research on the relationship between GHR mutation and lipid metabolism in GHR KO pigs and siGHR-treated human liver cells showed that GHR loss disrupts the ERK-AHR-ACOX1/CPT1A pathway, leading to hepatic steatosis. AHR has been identified as a key modulator of lipid metabolism disorder and a potential therapeutic target for hepatic steatosis. The study sheds light on the molecular mechanisms underlying lipid metabolism abnormalities in LS and provides new insights for developing treatments.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Nutrition & Dietetics
Rosaria Maria Pipitone, Rossella Zito, Giuditta Gambino, Gabriele Di Maria, Ayesha Javed, Giulia Lupo, Giuseppe Giglia, Pierangelo Sardo, Giuseppe Ferraro, Francesca Rappa, Daniela Carlisi, Danila Di Majo, Stefania Grimaudo
Summary: Nonalcoholic fatty liver disease (NAFLD) is a health emergency worldwide and there is no standard therapy available for it. This study found that dietary supplementation with red and golden tomatoes can significantly reduce triglycerides, low-density lipoprotein-cholesterol, fasting glucose, and homeostasis model assessment index, while increasing high-density lipoprotein-cholesterol. The study also found that the consumption of tomatoes can regulate the expression of genes involved in metabolic homeostasis, adipokine signaling, and inflammatory response, suggesting their potential in preventing and treating NAFLD.
FRONTIERS IN NUTRITION
(2023)
Article
Agriculture, Dairy & Animal Science
Yan Deng, Junsong Yuan, Jiamin Qiu, Bincheng Tang, Xuefei Chen, Shenqiang Hu, Hua He, Hehe Liu, Liang Li, Chunchun Han, Jiwei Hu, Jiwen Wang
Summary: Evidence suggests that estrogen may up-regulate the expression levels of proteins related to lipid transportation, thereby alleviating lipid overload in hepatic steatosis of geese in vitro.
JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
(2022)
Review
Biochemistry & Molecular Biology
Georgiana-Diana Cazac, Cristina-Mihaela Lacatusu, Catalina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
Summary: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease associated with metabolic syndrome. The development of non-invasive diagnostic methods to replace liver biopsy in high-risk patients, especially those with type 2 diabetes, is crucial. Elastographic methods can improve screening and diagnosis of NAFLD in diabetes patients and guide treatment. This review focuses on ultrasound-based hepatic elastography for NAFLD assessment in patients with diabetes.
Article
Acoustics
Tu-Yung Chang, Shu-Hung Chang, Ying-Hsiu Lin, Wen-Chao Ho, Chiao-Yin Wang, Wen-Juei Jeng, Yung-Liang Wan, Po-Hsiang Tsui
Summary: This study investigated the utility of quantitative ultrasound for screening hepatic steatosis and metabolic evaluation at the community level. The results showed that ultrasound ISE could be a potential imaging biomarker during first-line community screening for hepatic steatosis and insulin resistance.
Article
Nutrition & Dietetics
Tymofiy Lutsiv, John N. McGinley, Elizabeth S. Neil, Michelle T. Foster, Henry J. Thompson
Summary: Hepatic steatosis indicates the beginning of metabolic dysfunction-associated fatty liver disease (MAFLD) due to disrupted metabolic homeostasis, which affects liver function. Regular consumption of common beans has been found to reduce the risk of metabolic impairment, but the required dose, the impact of biological sex, and the underlying mechanisms are unknown. In this study, female and male mice were fed obesogenic yet isocaloric diets containing different amounts of protein derived from cooked whole common beans. The results showed that beans reduced hepatic fat deposition at specific doses in both female and male mice. The differentially expressed genes (DEGs) induced by beans were mainly involved in hepatic steatosis and demonstrated dose-responsive inhibition of de novo lipogenesis markers, activation of triacylglycerol degradation, and downregulation of SREBF1 signaling. Additionally, the effects of beans on fatty acid metabolism differed between females and males. The findings suggest that the amount of common beans in the diet required to prevent hepatic lipid accumulation depends on biological sex.
Article
Behavioral Sciences
Helen J. Rushby, Zane B. Andrews, Matthew D. W. Piper, Christen K. Mirth
Summary: Modifying the proportions of macronutrients in the diet has significant effects on the reproduction and health of animals. In this study, using capillary feeding assays, we explored how adult fruit flies compromise their nutrient intake when limited to single diets. We found that young male and female flies compromised by consuming more food on diets with low protein to carbohydrate ratios. Additionally, female flies showed greater variations in carbohydrate intake compared to males, and mated females consumed more food than virgin females.
Article
Endocrinology & Metabolism
Romana Stark, Jack Feehan, Aya Mousa, Zane B. B. Andrews, Barbora de Courten
Summary: This study identified an association between liver-expressed antimicrobial peptide 2 (LEAP2) levels and key cardiometabolic risk factors in individuals with overweight and obesity, including body fat, insulin secretion, and insulin resistance. LEAP2 may represent a potential therapeutic target to promote insulin secretion in individuals with type 2 diabetes and obesity.
DIABETES OBESITY & METABOLISM
(2023)
Article
Developmental Biology
Samuel R. Cheers, Anne E. O'Connor, Travis K. Johnson, D. Jo Merriner, Moira K. O'Bryan, Jessica E. M. Dunleavy
Summary: This study reveals the crucial role of spastin, a member of the meiotic AAA ATPase protein clade, in regulating microtubule dynamics during spermatogenesis. Spastin loss leads to a complete loss of functional germ cells, enlarged spermatid nuclei with aneuploidy, and severe abnormalities in manchette structure and acrosome biogenesis. These findings have potential relevance to individuals carrying spastin variants and to the medically assisted reproductive technology industry.
Article
Public, Environmental & Occupational Health
Sarah N. Biggs, Joanne Kennedy, Sharon L. Lewis, Stephen Hearps, Moira K. O'Bryan, Robert McLachlan, Simon von Saldern, Georgina Chambers, Jane Halliday
Summary: Approximately 1 in 20 men are sub-fertile or infertile, but the causes of male infertility are not well understood. This study aims to recruit 1000 Australian male partners seeking help from fertility clinics to investigate the factors associated with male infertility. The findings will provide important information for clinicians and inform public policy on prevention and treatment strategies for infertile men.
REPRODUCTIVE HEALTH
(2023)
Article
Cell Biology
Nicola D. Kolaitis, Bethany J. Finger, D. Jo Merriner, Joseph Nguyen, Brendan J. Houston, Moira K. O'Bryan, Jessica M. Stringer, Nadeen Zerafa, Ngoc Nguyen, Karla J. Hutt, Gerard A. Tarulli, Mark P. Green
Summary: This study found that chronic exposure to an environmentally relevant concentration of the herbicide atrazine affects male fertility in mice, particularly by altering the expression of steroidogenic genes in the testicles. Further research should be conducted to investigate the multigenerational effects of atrazine on male fertility.
Article
Developmental Biology
Jessica E. M. Dunleavy, Maddison Graffeo, Kathryn Wozniak, Anne E. O'Connor, D. Jo Merriner, Joseph Nguyen, Ralf B. Schittenhelm, Brendan J. Houston, Moira K. O'Bryan
Summary: This study reveals that multiple katanin A-subunit paralogs play important roles in various processes during mammalian spermatogenesis, including the construction of the meiotic spindle, cytokinesis, midbody abscission, and spermatid remodelling. The study also identifies specific roles of certain genes in sperm flagellum development and interaction networks with other proteins.
Article
Urology & Nephrology
Sarah Kimmins, Richard A. Anderson, Christopher L. R. Barratt, Hermann M. Behre, Sarah R. Catford, Christopher J. De Jonge, Geraldine Delbes, Michael L. Eisenberg, Nicolas Garrido, Brendan J. Houston, Niels Jorgensen, Csilla Krausz, Ariane Lismer, Robert I. Mclachlan, Suks Minhas, Tim Moss, Allan Pacey, Laerke Priskorn, Stefan Schlatt, Jacquetta Trasler, Leonardo Trasande, Frank Tuettelmann, Monica Hebe Vazquez-Levin, Joris A. Veltman, Feng Zhang, Moira K. O'Bryan
Summary: Currently, there is a lack of understanding and awareness about the causes of male infertility and the importance of male reproductive health. This leads to standardized treatment strategies using medically assisted reproduction techniques, which overlook the potential co-morbidities and shift the burden to women. To improve male reproductive health, it is essential to establish centers for data and sample collection and study the effects of genetics, epigenetics, and environment on fertility and offspring health. Personalized treatment protocols should be developed and education about infertility should be increased.
NATURE REVIEWS UROLOGY
(2023)
Article
Urology & Nephrology
Margot J. Wyrwoll, Godfried W. van der Heijden, Csilla Krausz, Kenneth I. Aston, Sabine Kliesch, Robert McLachlan, Liliana Ramos, Donald F. Conrad, Moira K. O'Bryan, Joris A. Veltman, Frank Tuettelmann
Summary: Discovering the genetic causes of non-syndromic male infertility and linking them with clinical data is crucial for better understanding the condition. The International Male Infertility Genomics Consortium has developed a standardized vocabulary based on the Human Phenotype Ontology (HPO) to facilitate communication and improve the classification of male infertility. This work will contribute to the systematic recording of patients' phenotypes and the discovery of novel genetic causes for non-syndromic male infertility.
NATURE REVIEWS UROLOGY
(2023)
Article
Biology
Madeleine J. De Jong, Lesley A. Alton, Craig R. White, Moira K. O'Bryan, David G. Chapple, Bob B. M. Wong
Summary: Incubation temperature has lasting effects on growth, locomotor performance, and metabolic rate of skink offspring. Cool and hot incubation temperatures result in faster growth and larger maximum size, while hot incubation temperatures reduce locomotor performance. Effects on metabolic rate are present in sub-adults, with higher rates in cool-incubated lizards. Additionally, cool and hot incubation treatments result in shorter sperm midpieces and heads.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Biology
Kaixin Huang, Laura K. Milton, Harry Dempsey, Stephen J. Power, Kyna-Anne Conn, Zane B. Andrews, Claire J. Foldi
Summary: Anorexia nervosa is a psychiatric disorder with a high mortality rate. Cognitive inflexibility is associated with the disorder, but it is unclear whether it predisposes individuals to anorexia nervosa. Previous animal studies using the activity-based anorexia model have shown a link between cognitive inflexibility and pathological weight loss. However, testing flexible learning in the same animals before exposure to the activity-based anorexia model has been difficult. This study presents a fully-automated and experimenter-free touchscreen cognitive testing system for rats and examines the relationship between reversal learning and weight loss in the activity-based anorexia model. The findings provide insights into the connection between cognitive inflexibility and pathological weight loss and offer potential targets for future research on pharmacotherapies for anorexia nervosa.
Article
Endocrinology & Metabolism
Felicia Reed, Alex Reichenbach, Harry Dempsey, Rachel E. Clarke, Mathieu Mequinion, Romana Stark, Sasha Rawlinson, Claire J. Foldi, Sarah H. Lockie, Zane B. Andrews
Summary: This study reveals that hunger and the environmental context can increase food-seeking behavior, and the activity of AgRP neurons plays a crucial role in this process. Precise temporal control of AgRP neuron activity is necessary for the development of the context-induced feeding response.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Wang Lok So, Jiachen Hu, Lotus Jeffs, Harry Dempsey, Sarah H. Lockie, Jeffrey M. Zigman, Romana Stark, Alex Reichenbach, Zane B. Andrews
Summary: The sensory detection of food suppresses AgRP neuronal activity, and ghrelin receptor signaling on AgRP neurons integrates energy need with external sensory cues to produce an optimal change in AgRP neural activity.
MOLECULAR METABOLISM
(2023)
Article
Cell Biology
Vanessa Tsui, Ruqian Lyu, Stevan Novakovic, Jessica M. Stringer, Jessica E. M. Dunleavy, Elissah Granger, Tim Semple, Anna Leichter, Luciano G. Martelotto, D. Jo Merriner, Ruijie Liu, Lucy McNeill, Nadeen Zerafa, Eva R. Hoffmann, Moira K. O'Bryan, Karla Hutt, Andrew J. Deans, Jorg Heierhorst, Davis J. McCarthy, Wayne Crismani
Summary: Meiotic crossovers are necessary for accurate chromosome segregation and generating new allelic combinations. This study reveals the role of the tumor suppressor FANCM as an anti-crossover factor in mammals and shows that Fancm deficiency leads to an increase in crossover frequencies.
Meeting Abstract
Biochemistry & Molecular Biology
Samuel Cheers, Miguel Xavier, Manon Oud, Petra de Vries, Bilal Alobaidi, Lois Batty, Liina Nagirnaja, Don Conrad, Kenneth Aston, Corinna Friedrich, Birgit Stallmeyer, Frank Tuettelmann, Godfried van der Heijden, Moira O'Bryan, Joris Veltman
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)