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metabolic models

Shin-Ichiro Ogawa, Yoshihiko Tunenari, Hiroyuki Kawai, Hiroshi Yamazaki
The metabolic profiles and pharmacokinetics of pemafibrate, a novel selective peroxisome proliferator activated receptor-alpha modulator currently launched as an antidyslipidemic drug, were investigated in vitro using hepatocytes from rats, monkeys, and humans and in vivo in rats and monkeys. Hepatocytes from rats, monkeys, and humans all biotransformed pemafibrate to its demethylated form (M1). The bioavailabilities of pemafibrate in Sprague-Dawley rats and cynomolgus monkeys were 15% and 87%, respectively, after a single oral administration of pemafibrate (1 mg/kg)...
December 5, 2018: Biopharmaceutics & Drug Disposition
Joseph P Argus, Moses Q Wilks, Quan D Zhou, Wei Yuan Hsieh, Elvira Khialeeva, Xen Ping Hoi, Viet Bui, Shili Xu, Amy K Yu, Eric S Wang, Harvey R Herschman, Kevin J Williams, Steven J Bensinger
It is well understood that fatty acids can be synthesized, imported, and modified to meet requisite demands in cells. However, following the movement of fatty acids through the multiplicity of these metabolic steps has remained difficult. To better address this problem, we developed Fatty Acid Source Analysis (FASA), a model that defines the contribution of synthesis, import, and elongation pathways to fatty acid homeostasis in saturated, monounsaturated, and polyunsaturated fatty acid pools. Application of FASA demonstrated that elongation can be a major contributor to cellular fatty acid content and showed that distinct pro-inflammatory stimuli (e...
December 4, 2018: Cell Reports
Kim G Harley, Kimberly P Berger, Katherine Kogut, Kimberly Parra, Robert H Lustig, Louise C Greenspan, Antonia M Calafat, Xiaoyun Ye, Brenda Eskenazi
STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls? SUMMARY ANSWER: We found some associations of altered pubertal timing in girls, but little evidence in boys. WHAT IS KNOWN ALREADY: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies...
December 4, 2018: Human Reproduction
Qing Peng, Carrie A Karvonen-Gutierrez, John F Randolph, Bin Nan, Daniel McConnell, Siobán D Harlow
Context: Women with polycystic ovary syndrome (PCOS) have a higher prevalence of metabolic syndrome (MetS), but whether they develop MetS earlier than women without PCOS is unknown. Understanding the impact of PCOS on the timing of MetS onset is important for screening and clinical care in this population. Design: Women with PCOS-like status ("PCOSp") were identified from participants of the Michigan Bone Health and Metabolism Study based upon history of irregular menstrual cycles, high free-androgen index and high levels of anti-müllerian hormone...
December 3, 2018: Journal of Clinical Endocrinology and Metabolism
Carlos Rp Dechandt, Tatiane M Vicentini, Guilherme Pauperio Lanfredi, Rui M P da Silva, Enilza Maria Espreafico, José A C de Oliveira, Vitor Marcel Faça, Norberto Garcia-Cairasco, Luciane C Alberici
The Wistar Audiogenic Rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister x brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing, however, is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of OXPHOS, oxidative stress, biogenesis and dynamics in liver, skeletal muscle and heart of male WAR, correlating then to physiological aspects of body metabolism...
December 5, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Cheuk-Ting Law, Lai Wei, Felice Ho-Ching Tsang, Cerise Yuen-Ki Chan, Iris Ming-Jing Xu, Robin Kit-Ho Lai, Daniel Wai-Hung Ho, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
Hepatocellular carcinoma (HCC) is the third lethal cancer worldwide. Increasing evidence showed that epigenetic alterations play an important role in human carcinogenesis. Deregulation of DNA methylation and histone modifications have recently been characterized in HCC, but the significance of chromatin remodeling in liver carcinogenesis remains to be explored. In this study, by systematically analyzing the expression of chromatin remodeling genes in human HCCs, we found that HELicase, Lymphoid-Specific (HELLS), a SWI2/SNF2 chromatin remodeling enzyme, was remarkably overexpressed in HCC...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
D Minukhina, V Babadzhan, D Minukhin, A Krasnoyaruzhskiy, D Yevtushenko
The combination of cardiac pathology and metabolic disorders, namely type 2 diabetes mellitus, is one of the most frequent comorbid pathologies and the main cause of death from cardiovascular complications at an early stage of the disease. Despite the wide range of antithrombogenic measures, prevention of thrombotic complications of acute myocardial infarction remains an urgent problem of cardiology. The study involved examination of 73 patients with acute myocardial infarction with concomitant type 2 diabetes mellitus, who were distributed into clusters according to severity by the main indices of lipid and carbohydrate metabolism using hierarchical analysis...
October 2018: Georgian Medical News
Haorong Li, Mengyang Xu, Jiangjiang Zhu
This study aimed to develop and incorporate a secondary electrospray ionization (SESI) setup in combination with both targeted tandem mass spectrometry (MS/MS) and a hybrid metabolomics technique, globally optimized targeted mass spectrometry (GOT-MS), to sensitively detect volatile metabolites from the headspace of in vitro gut microbial culture in a human colonic model (HCM). Two SESI- tandem mass spectrometry panels with a comparable number of targeted metabolites/features (77 compounds in the targeted SESI-MS/MS panel, and 75 features in the SESI-GOT-MS/MS panel) were established...
December 5, 2018: Analytical Chemistry
Irene Headen, Barbara Laraia, Kimberly Coleman-Phox, Cassandra Vieten, Nancy Adler, Elissa Epel
OBJECTIVE: This study aimed to assess associations between neighborhood typologies classified across multiple neighborhood domains and cardiometabolic pregnancy outcomes and determine variation in effectiveness of a mindfulness-based stress-reduction intervention on outcomes across neighborhood types. METHODS: Neighborhoods of participants in the Maternal Adiposity Metabolism and Stress (MAMAS) intervention (n = 208) were classified across dimensions of socioeconomic, food, safety, and service/resource environments using latent class analysis...
December 4, 2018: Obesity
Noriaki Kawanishi, Tsubasa Mizokami, Koichi Yada, Katsuhiko Suzuki
Although nonalcoholic steatohepatitis (NASH) is an important component of the metabolic syndrome, scavenger receptor CD36 also modulates NASH development. This study aimed to clarify whether exercise training suppresses CD36 expression in a mouse model of NASH. Male C57BL/6 mice were divided into four groups: normal diet (ND) sedentary, ND exercise, high-fat diet and high-fructose water (HFF) sedentary, and HFF exercise groups. The exercise groups were trained on a motorized treadmill at running speeds of 15-20 m/min for 60 min/day, 5 times/week for 16 weeks...
December 2018: Physiological Reports
Christian Krug, Anita Beer, Bastian Hartmann, Carina Prein, Hauke Clausen-Schaumann, Thomas Holzbach, Attila Aszodi, Riccardo Enzo Giunta, Maximilian Michael Saller, Elias Volkmer
Adipose-derived multipotent stem/progenitor cells (ASPCs) were shown to be ideal candidates for cell-based regenerative therapies. Yet, despite their huge potential, successful clinical applications are still rare. It was suggested that the efficacy of ASPCs at the recipient site depends on the vehicle of cell delivery. In this study, for preparation of a murine critical-size nerve defect model, we assessed the commercially available fibrin gel (ARTISS) as a potential cell carrier. In a thorough in vitro analysis, we investigated cell-fibrin interactions, and analyzed the distribution and the long-term behavior of ASPCs cultivated in fibrin gel under normoxic and hypoxic conditions...
December 4, 2018: Journal of Tissue Engineering and Regenerative Medicine
Xiaoying Lian, Xiaoyuan Wu, Zhongxin Li, Yingjie Zhang, Kangkang Song, Guangyan Cai, Qinggang Li, Shupeng Lin, Xiangmei Chen, Xue-Yuan Bai
BACKGROUND AND PURPOSE: The pathogenic mechanism of autosomal dominant polycystic kidney disease (ADPKD) is unclear. Similar to tumor cells, polycystic kidney cells are primarily dependent on aerobic glycolysis for ATP production. Compared with rodents, miniature pigs are more similar to humans. This study is the first time to investigate the effects of the combination of metformin and 2DG in a chronic progressive ADPKD miniature pig model. EXPERIMENTAL APPROACH: A miniature pig ADPKD model was established by inducible deletion of the PKD1 gene...
December 4, 2018: British Journal of Pharmacology
Angela T S Wyse, Mateus Grings, Moacir Wajner, Guilhian Leipnitz
Sulfite oxidase (SO) deficiency is an autosomal recessive inherited neurometabolic disease caused by deficient activity of SO. It is biochemically characterized by tissue accumulation and high urinary excretion of sulfite, thiosulfate, and S-sulfocysteine. Severe neurological symptoms, including neonatal seizures, encephalopathy, and psychomotor retardation, are commonly observed in the affected patients, but the pathogenesis of the neurologic dysfunction is still poorly understood. In this minireview, we will briefly summarize the knowledge obtained from in vivo and in vitro findings from animal studies indicating that oxidative stress and mitochondrial dysfunction are involved in the pathophysiology of the brain damage in this disease...
December 5, 2018: Neurotoxicity Research
Wenqi Gao, Wei Wang, Gang Liu, Jing Zhang, Jian Yang, Zhifang Deng
Allicin, one of the main biologically active compounds derived from garlic, was previously reported to possess multiple pharmacological activities. Whether allicin protected against chronic social defeat stress (CSDS) induced depressive-like behaviors remained unknown. Thus, our present study for the first time investigated the potential antidepressant effects and the mechanisms of allicin on the CSDS mice model. Thirty minutes before social defeat stress, allicin (2, 10, 50 mg/kg) was treated by intraperitoneal injection...
December 4, 2018: Metabolic Brain Disease
Dandan Cao, Bin He, Yongguang Yin
Ethylmercury (EtHg) has been widely observed in the environment due to anthropogenic contamination and/or environmental ethylation of inorganic mercury. Herein, the acute and sublethal effect of EtHg chloride on Chinese rare minnow (Gobiocypris rarus) as a fish model was studied. EtHg chloride showed an obvious toxicity to 4-month-old Chinese rare minnow (LC50 24.8 µg L-1 (as Hg) at 24 h). Histological analysis revealed that acute EtHg exposure can induce necrosis, telangiectasis and exfoliation of epithelial cells in the gill, as well as edema, vacuoles, and pyknotic nuclei in hepatocytes...
December 4, 2018: Bulletin of Environmental Contamination and Toxicology
Isaac Asante, Hua Pei, Eugene Zhou, Siyu Liu, Darryl Chui, EunJeong Yoo, David V Conti, Stan G Louie
INTRODUCTION: colorectal cancer (CRC) continues to be difficult to diagnose due to the lack of reliable and predictive biomarkers. OBJECTIVE: to identify blood-based biomarkers that can be used to distinguish CRC cases from controls. METHODS: a workflow for untargeted followed by targeted metabolic profiling was conducted on the plasma samples of 26 CRC cases and ten healthy volunteers (controls) using liquid chromatography-mass spectrometry (LCMS)...
December 5, 2018: Molecular omics
Yunkyoung Lee, Hyunhee Oh, Myoungsook Lee
BACKGROUND/OBJECTIVES: Gelidium amansii ( GA ) contains plenty of agars and various biological substances, which make them a popular functional food to control body weight in previous studies. Unlike previous studies focused on agar in GA, objectives of this study were to investigate the effects of agar-free GA extract ( AfGAE ) on preventive and treatment models by using diets-induced obese (DIO) C57BL/6J mice. MATERIALS/METHODS: Af GAE were used to test their effects on the prevention ( Exp-1 ) and treatment ( Exp-2 ) against obesity after pilot study in DIO mice...
December 2018: Nutrition Research and Practice
Adugna Abdi Woldesemayat, Monde Ntwasa
Drought alone or in combination with other stresses forms the major crop production constraint worldwide. Sorghum, one of the most important cereal crops is affected by drought alone or in combination with co-occurring stresses; notwithstanding, sorghum has evolved adaptive responses to combined stresses. Furthermore, an impressive number of sorghum genes have been investigated for drought tolerance. However, the molecular mechanism underling drought response remains poorly understood. We employed a systems biology approach to elucidate regulatory and broad functional features of these genes...
2018: Frontiers in Genetics
Tytti Heinonen, Eleonora Ciarlo, Charlotte Théroude, Aimilia Pelekanou, Jacobus Herderschee, Didier Le Roy, Thierry Roger
Sirtuin 5 (SIRT5) is a member of the family of NAD+ -dependent lysine/histone deacetylases. SIRT5 resides mainly in the mitochondria where it catalyzes deacetylation, demalonylation, desuccinylation, and deglutarylation of lysine to regulate metabolic and oxidative stress response pathways. Pharmacologic inhibitors of SIRT5 are under development for oncologic conditions, but nothing is known about the impact of SIRT5 on antimicrobial innate immune defenses. Using SIRT5 knockout mice, we show that SIRT5 deficiency does not affect immune cell development, cytokine production and proliferation by macrophages and splenocytes exposed to microbial and immunological stimuli...
2018: Frontiers in Immunology
Martine Van Puyvelde, Xavier Neyt, Francis McGlone, Nathalie Pattyn
People rely on speech for communication, both in a personal and professional context, and often under different conditions of physical, cognitive and/or emotional load. Since vocalization is entirely integrated within both our central (CNS) and autonomic nervous system (ANS), a mounting number of studies have examined the relationship between voice output and the impact of stress. In the current paper, we will outline the different stages of voice output, i.e., breathing, phonation and resonance in relation to a neurovisceral integrated perspective on stress and human performance...
2018: Frontiers in Psychology
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