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Jun‐Xue Jin Sanghoon Lee Anukul Taweechaipaisankul Geon A. Kim Byeong Chun Lee 《Journal of pineal research》2017,62(2)
It is being increasingly recognized that the processes of lipogenesis and lipolysis are important for providing an essential energy source during oocyte maturation and embryo development. Recent studies demonstrated that melatonin has a role in lipid metabolism regulation, including lipogenesis, lipolysis, and mitochondrial biogenesis. In this study, we attempted to investigate the effects of melatonin on lipid metabolism during porcine oocyte in vitro maturation. Melatonin treatment significantly enhanced the number of lipid droplets (LDs) and upregulated gene expression related to lipogenesis (ACACA, FASN, PPARγ, and SREBF1). Oocytes treated with melatonin formed smaller LDs and abundantly expressed several genes associated with lipolysis, including ATGL, CGI‐58, HSL, and PLIN2. Moreover, melatonin significantly increased the content of fatty acids, mitochondria, and ATP, as indicated by fluorescent staining. Concomitantly, melatonin treatment upregulated gene expression related to fatty acid β‐oxidation (CPT1a, CPT1b, CPT2, and ACADS) and mitochondrial biogenesis (PGC‐1α, TFAM, and PRDX2). Overall, melatonin treatment not only altered both the morphology and amount of LDs, but also increased the content of fatty acids, mitochondria, and ATP. In addition, melatonin upregulated mRNA expression levels of lipogenesis, lipolysis, β‐oxidation, and mitochondrial biogenesis‐related genes in porcine oocytes. These results indicated that melatonin promoted lipid metabolism and thereby provided an essential energy source for oocyte maturation and subsequent embryonic development. 相似文献
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Sandrine Lemoine René Rouet Alain Manrique Jean‐Luc Hanouz 《Fundamental & clinical pharmacology》2014,28(5):481-488
Lipid emulsions are used in the reversal of local anesthetic toxicity. The aim of this study was to investigate the cellular electrophysiological effects of long‐chain triglyceride lipid emulsion (LCTE) on cardiac action potential characteristics and conduction disturbances induced by bupivacaine. Purkinje fibers were dissected from the left ventricle of New Zealand white rabbit hearts and superfused with either Tyrode's solution during 30 min (control group), with bupivacaine 10?6 m , 10?5 m , and 5.10?5 m alone, or in the presence of LCTE 0.5%, in addition, LCTE at 0.1%, 0.5%, and 1% was perfused alone. Electrophysiological parameters were recorded using the conventional microelectrode technique (37 °C, 1 Hz frequency). Bupivacaine 5.10?5 m ‐induced conduction blocks (8/8 preparations): LCTE 0.5% suppressed the bupivacaine 5.10?5 m ‐induced conduction blocks (1/8 preparations). Exposure to bupivacaine 10?6 m , 10?5 m , and 5.10?5 m resulted in a significant decrease in the maximal rate of depolarization (Vmax) (respectively, 25%, 55%, 75%; P < 0.002 vs. control group). In the presence of LCTE 0.5%, bupivacaine 10?6 m did not significantly decreased Vmax (13%; P = 0.10 vs. control group). The decrease in Vmax resulting from bupivacaine 10?5 m alone was significantly less in the presence of LCTE 0.5% (P < 0.01 vs. bupivacaine 10?5 m alone). Exposure to bupivacaine 10?6 m , 10?5 m , and 5.10?5 m alone or in the presence of LCTE 0.5% resulted in a significant decrease in action potential duration measured at 50% and 90% repolarization (APD50 and APD90; P < 0.01 vs. control group). LCTE inhibited the Purkinje fibers conduction blocks induced by bupivacaine. Moreover, LCTE 0.5% attenuates the decrease in Vmax induced by bupivacaine 10?6 m and 10?5 m . 相似文献
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《药学学报(英文版)》2021,11(8):2469-2487
Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs. 相似文献
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《Expert opinion on therapeutic patents》2013,23(10):1317-1335
Introduction: The development of small molecule agonists of the liver X receptors (LXRs) has been an area of interest for over a decade, given the critical role of those receptors in cholesterol metabolism, glucose homeostasis, inflammation, innate immunity and lipogenesis. Many potential indications have been characterized over time including atherosclerosis, diabetes, inflammation, Alzheimer's disease and cancer. However, concerns about the lipogenic effects of full LXRα/β agonists have required extensive efforts aimed at identifying LXRβ agonist with limited activity on the LXRα receptor to increase the safety margins. Areas covered: This review includes a summary of the LXR agonists that have reached the clinic and summarizes the patent applications for LXR modulators from September 2009 to December 2012 with emphasis on chemical matters, biological data associated with selected analogs and therapeutic indications. Expert opinion: As LXR agonists have the potential to be useful for many indications, the scientific community, despite setbacks due to on-target side effects, has maintained interest and devised strategies to overcome safety hurdles. While a clinical proof of concept still remains elusive, the recent advancement of compounds into the clinic highlights that acceptable safety margins in preclinical species have been achieved. 相似文献
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目的:探讨孕晚期游离脂肪酸对子痫前期和(或)妊娠期糖尿病(GDM)发病率的影响。方法:选择417例孕晚期子痫前期和(或)GDM为观察组,另选2 018例正常妊娠孕妇为对照组。检测并比较2组血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和游离脂肪酸(FFA)。采用logistic回归模型分析血脂子痫前期和(或)GDM的关系。结果:校正混杂因素[孕妇年龄、孕前体质指数(BMI)和采血时的孕周]后,孕晚期FFA浓度升高会增加子痫前期、GDM和子痫前期合并GDM的风险(P0.01)。孕晚期TG水平升高会增加子痫前期、GDM发生的风险(P0.001)。结论:孕晚期FFA水平升高可使子痫前期和(或)GDM发生风险增加。 相似文献
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Eiryu Sai Kazunori Shimada Tatsuro Aikawa Chihiro Aoshima Kazuhisa Takamura Makoto Hiki Takayuki Yokoyama Tetsuro Miyazaki Shinichiro Fujmoto Hakuoh Konishi Ken-ichi Hirano Hiroyuki Daida Tohru Minamino 《Internal medicine (Tokyo, Japan)》2021,60(8):1217
The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (1H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using 1H-MRS noninvasively. 相似文献