Intracellular lipid droplets (LDs) are found in a wide variety of cell types and have been recognized as organelles with unique spherical structures. Although LDs are not stable lipid-depots, they ...are active sites of neutral lipid metabolism, and comprise neutral lipid or cholesterol cores surrounded by phospholipid monolayers containing specialized proteins. However, sizes and protein compositions vary between cell and tissue types. Proteins of the perilipin family have been associated with surfaces of LDs and all carry a conserved 11-mer repeat motif. Accumulating evidence indicates that all perilipins are involved in LD formation and that all play roles in LD function under differing conditions. In this brief review, we summarize current knowledge of the roles of perilipins and lipid metabolizing enzymes in a variety of mammalian cell types.
Second generation antipsychotics are useful for the treatment of schizophrenia, but concerns have been raised about the side effects of diabetes mellitus and obesity. Olanzapine, especially, is ...associated with more weight gain than the others. It has been reported that olanzapine promotes adipocyte-differentiation in rodents both in vivo and in vitro. In this study the effects of antipsychotics on human adipocytes were investigated by using human mesenchymal stem cells (hMSCs). When hMSCs were differentiated and treated with various antipsychotics, olanzapine and clozapine increased intracellular lipids. Olanzapine induced lipid accumulation in a dose-dependent manner. Proteomic analysis revealed that PLIN4 and several enzymes for lipid metabolism were increased in the hMSCs after olanzapine treatment. During adipocyte differentiation, olanzapine increased the protein expression of PLIN1, PLIN2 and PLIN4. These proteins are known to be associated with the initial stage of lipid droplet formation. Immunocytochemistry showed that olanzapine increased and enlarged the lipid droplets coated with PLIN1 and PLIN2 while PLIN4 was largely distributed in the cytosol. mRNA expression of PLIN2, but not PLIN1 or PLIN4, was increased by olanzapine. On the other hand, olanzapine did not alter the mRNA level of transcription regulators involved in adipocyte-differentiation or adipokines. The present study shows that olanzapine induced transient PLIN2 expression in hMSCs that could result in an accumulation of lipid droplets and overexpression of PLIN1 and PLIN4, providing information of possible interest for olanzapine-induced weight gain.
•The effect of antipsychotics on human adipocytes was investigated by using human mesenchymal stem cells (hMSCs).•Olanzapine and clozapine, which are known for a side effect of obesity, increased lipids in hMSC-derived adipocytes.•Protein expression of perilipins (PLIN1, 2, 4) was increased by olanzapine treatment.•Olanzapine increased transient increase in PLIN2 which could lead to formation of enlarged lipid droplets.
Lipid droplets (LDs) are functional subcellular organelles involved in multiple intracellular processes. LDs are found in nearly all types of eukaryotic cells, but their properties are highly ...variable in different types of tissues. Steroidogenic cells synthesize steroid hormones de novo from the cholesterol deposited in cytosolic LDs. However, the roles of LD proteins in steroidogenesis under pituitary hormone stimulation have not been well elucidated. The protein profile of isolated LDs from the mouse Leydig tumor cell line MLTC-1 was distinct from that of hepatic cells or macrophages. By proteomic analysis of the components using mass spectrometry, two enzymes for steroidogenesis, 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) and 17 β-hydroxysteroid dehydrogenase type 11 (17βHSD11), were identified in two strong bands in the LD fractions. The LD fraction of MLTC-1 cells also included CYP11A1 and CYP17, suggesting that the LDs contain all the enzymes needed for testosterone synthesis. The steroidogenesis in Leydig cells is activated by luteinizing hormone through a PKA-dependent pathway. Stimulation of MLTC-1 cells with luteinizing hormone or 8-bromo-cAMP caused drastic changes in the morphology of the LDs in the MLTC-1 cells. Upon stimulation, large perinuclear LDs are turned into much smaller LDs and dispersed throughout the cytosol. These results raise the possibility that LDs are involved in a regulatory pathway of steroidogenesis, not just by serving as a storage depot for cholesterol esters, but also by providing enzymes and generating sites for enzymatic activity.
•Protein profile of lipid droplets from MLTC-1 mouse Leydig cell line was studied.•The LDs contain steroidogenic enzymes including 3βHSD1 and 17βHSD11.•Luteinizing hormone changes the size and distribution of lipid droplets.•The LDs may provide not only the substrates but enzymes and sites of steroidogenesis.
Background
Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the ...circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS.
Methods
We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects.
Results
The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 μg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low.
Conclusions
In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.
Tolvaptan is a key drug for patients with heart failure. Here, we present a 92‐year‐old woman, whose PT‐INR/dose increased from 1.74 to 3.30 after warfarin and tolvaptan co‐administration, and ...resulted in a large cerebral infarction after warfarin dose down. Therefore, the interaction between these two drugs may be clinically significant.
Our case showed that an increase in PT‐INR potentially resulted in a drug‐drug interaction between tolvaptan and warfarin, which are frequently co‐administered in patients with heart failure. Thus, when both drugs are co‐administered, it is necessary to closely monitor the PT‐INR of patients.
This study aimed to determine the accuracy of the evaluation system for LM1010 （HITACHI High-Tech Science, Tokyo, Japan） based on high-performance liquid chromatography coupled with ...ultraviolet-visible spectroscopy for therapeutic drug monitoring of the active metabolite mycophenolic acid （MPA） of mycophenolate mofetil （MMF） following renal transplantation and immunosuppressant therapy. We included six patients （including 4 males and 2 females; mean age, 49±13 years） who provided written informed consent. Blood sampling was performed at 0, 1, 2, 3, 4, 6, and 9hr after the administration of 750mg of MMF. The resulting measurements using the LM1010 method and the outsourcing method, high-performance liquid chromatography-mass spectrometry （HPLC-MS/MS）, were compared. The serum concentration of MPA was not significantly different between the LM1010 and HPLC-MS/MS methods for the 42 samples from six patients （4.2±3.5 vs. 4.5±4.1µg/ml）. MPA measurements were correlated with LM1010 and HPLC-MS/MS （r2＝0.9459）. No significant differences in pharmacokinetic parameters, that is, peak serum concentration （Cmax） （8.6±4.7 vs. 8.9±5.7µg/ml）, time to peak serum concentration （Tmax） （2.4±1.1 vs. 2.4±1.1hr）, estimated serum concentration 12hr after oral administration （C12） （1.3±1.6 vs. 1.4±1.8µg/ml）, and area under the serum concentration-time curve 0-12hr after oral administration （AUC0-12） （40.6±28.2 vs. 36.9±34.1µg/ml）, were observed between LM1010 and HPLC-MS/MS. In clinical settings, LM1010 can help determine the MPA concentration in patients treated with MMF after renal transplantation.
Objective: We designeda guideline for the use of in-line filters and infusion-tubing for infusion to improve the effectiveness and safety of infusion treatment in October 2016. The purpose of this ...study was to investigate the implication of the design and evaluation of usability of this guideline.Design and Methods: We conducted a questionnaire survey regarding this guideline among pharmacists and nurses in our hospital between January and February 2018. In addition, we investigated the inquiries made to the division of drug information (DI) and the reports of incidents from 2008 to 2019 and extractedcontent regarding in-line filters. We counted the number of reports relatedto in line filters per year, the kindof drugs, and time taken to address inquiries, and comparedthese with every 3 years before this guideline was made public and 3 years after publishing this guideline.Results: For “know” this guideline, the number of pharmacists was 40 (75%) and the number of nurses was 197 (57%). For “use” this guideline, the number of pharmacists was 29 (55%) and the number of nurses was 94 (27%). The average number of inquiries made to the division of DI was 4.7 for 2014-2016 and 1.7 for 2017-2019. The average number of reports of incidents was 8.3 for 2014-2016 and 6.0 for 2017-2019.Conclusion: This guideline tended to decrease the number of inquiries made to the division of DI and reports of incidents. Therefore, we suggest that this guideline contributedto the mitigation of the work loadof the division of DI and the effectiveness and safety of infusion treatment.
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