Osteocalcin downregulates pancreatic lipase expression in GPRC6A dependent manner

2016 ◽  
Author(s):  
Kyunghwa Baek ◽  
Seong-Hee Ko ◽  
Hyo Rin Hwang ◽  
Yewon Kwon ◽  
Jeong-Hwa Baek
2021 ◽  
Vol 29 (1) ◽  
pp. 76-86
Author(s):  
Wendi Nurul Fadillah ◽  
Nampiah Sukarno ◽  
Dyah Iswantini ◽  
Min Rahminiwati ◽  
Novriyandi Hanif ◽  
...  

This study aimed to evaluate the potential of marine fungus Purpureocillium lilacinum isolated from an Indonesian marine sponge Stylissa sp. as an anti-obesity agent through pancreatic lipase inhibition assay. The fungus was identified as P. lilacinum through morphological and molecular characteristics. The fungal extract’s inhibition activity and kinetics were evaluated using spectrophotometry and Lineweaver-Burk plots. Ethyl acetate and butanol were used for extraction. Both extracts showed pancreatic lipase inhibition in a concentration-dependent manner. Both crude extracts were then fractionated once. All fractionated extracts showed inhibitory activity above 50%, with the highest activity found in fraction 5 of ethyl acetate at 93.41% inhibition. The best fractionated extract had an IC50value of 220.60 µg.mL-1. The most active fraction of P. lilacinum had a competitive-type inhibitor behavior as shown by the value of Vmax not significantly changing from 388.80 to 382.62 mM pNP.min-1, and the Michaelis-Menten constant (KM) increased from 2.02 to 5.47 mM in the presence of 500 µg.mL-1 fractionated extract. Metabolite identification with LC-MS/MS QTOF suggested that galangin, kaempferol, and quercetin were responsible for the observed lipase inhibition.


2021 ◽  
Vol 22 (3) ◽  
pp. 1262
Author(s):  
Yukiko Matsuo ◽  
Asuka Yamashiro ◽  
Kanae Ootomo ◽  
Mika Nakagawa ◽  
Hiroko Tsuchihashi ◽  
...  

Scilla species are used as medicinal plants and contain lanosterol-type triterpene glycosides. The phytochemical investigation of the bulbs of Scilla peruviana led to the isolation of 17 compounds, including three new rearranged pentacyclic-lanosterol glycosides (1–3) and two new homoisoflavanone glycosides (12 and 13). The structures of the undescribed compounds were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Among the triterpene glycosides, 2, 3, and 6 showed significant pancreatic lipase inhibitory activity in a concentration-dependent manner in vitro. The oral administration of scillascilloside D-2 (6) reduced serum triglyceride levels in a dose-dependent manner in soybean oil-loaded mice.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Kanokwan Tiamyom ◽  
Kittipot Sirichaiwetchakoon ◽  
Tanaporn Hengpratom ◽  
Sajeera Kupittayanant ◽  
Rungrudee Srisawat ◽  
...  

This study aimed to investigate the effects of Cordyceps sinensis extract (CSE) and Gymnema inodorum extract (GIE), used alone and combined, on antiadipogenesis in 3T3-L1 cells. Oil Red O staining was used to examine the effects of these extracts on inhibition of intracellular lipid accumulation in 3T3-L1 adipocytes and on lipid droplet morphology. Fourier transform-infrared (FTIR) microspectroscopy was used to examine biomolecular changes in 3T3-L1 adipocytes. The pancreatic lipase assay was used to evaluate the inhibitory effects of CSE and GIE on pancreatic lipase activity. Taken together, the results indicated that CSE, GIE, and their combination suppressed lipid accumulation. The FTIR microspectroscopy results indicated that CSE, GIE, and their combination had inhibitory effects on lipid accumulation in the adipocytes. Compared with the untreated adipocytes, the signal intensity and integrated areas of glycogen and other carbohydrates, the acyl chain of phospholipids, and the lipid/protein ratios of the CSE, GIE, alone, and combined treated adipocytes were significantly lower (p < 0.05). Combination treatment resulted in a synergistic effect on lipid accumulation reduction in the adipocytes. Principal component analysis of the biomolecular changes revealed six distinct clusters in the FTIR spectra of the sample cells. The pancreatic lipase assay results indicated that CSE and GIE inhibited the pancreatic lipase activity in a dose-dependent manner (mean ± standard error of the mean IC50 values, 2312.44 ± 176.55 μg mL−1 and 982.24 ± 44.40 μg mL−1, resp.). Our findings indicated that FTIR microspectroscopy has potential application for evaluation of the effectiveness of medicinal plants and for the development of infrared biochemical obesity markers useful for treating patients with obesity. These results suggested that use of CSE and GIE alone and in combination may be efficacious as a complementary therapy for hyperlipidemia and obesity management. However, clinical trials in animals and humans must first be completed.


2019 ◽  
Vol 21 (1) ◽  
pp. 1 ◽  
Author(s):  
Saira Hussain ◽  
Ata Ur Rehman ◽  
David J. Luckett ◽  
Christopher L. Blanchard ◽  
Hassan K. Obied ◽  
...  

The extraction of phenolic compounds from canola meal produces functional health products and renders the canola meal a more digestible animal feed. The extracted phenolics may have novel bioactivity worth investigation. In this study, several solvents were evaluated for their ability to extract phenolic compounds from canola meal: water (WE) and various 80% organic solvent/water mixtures of methanol (ME), acetone (AE), ethanol (EE), butanol (BE), chloroform (CE) and hexane (HE). The in vitro antioxidant and anti-obesity properties of various extracts were investigated. Anti-obesity properties were studied using adipogenic differentiation inhibition of a murine mesenchymal stem cell line (C3H10T1/2) and a pancreatic lipase inhibition assay. AE, ME, and BE showed significant (p < 0.05) adipogenesis and pancreatic lipase inhibitory activities and may have more pharmacological properties. AE down-regulated the gene expression of the major adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), correlating to phenolic content in a dose-dependent manner. The chemical characterization of AE revealed the presence of sinapic acid, ferulic acid, and kaempferol derivatives as main bioactive phenols.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Cecilia Moreno Valdespino ◽  
Elvira Gonzalez de Mejia ◽  
Luis Mojica ◽  
Diego Luna-Vital ◽  
Rosa Camacho

Abstract Objectives Food-based products such as common bean peptides may contribute to reduce the risk of complications associated with obesity. The objective of this research was to produce and characterize peptides from common bean protein isolates and evaluate their potential to prevent adipogenesis. Methods Protein hydrolysates of raw common black bean (BBPH) were generated using a simulated gastrointestinal digestion by either pepsin/pancreatin (p/p) or a protease: alcalase. SDS-PAGE was performed for visualization of the protein profile and the generated peptides were characterized using LC-ESI-MS/MS. Bioactive peptides potential was evaluated using BIOPEP database. The antiadipogenic potential was evaluated by the pancreatic lipase (triglyceride lipases, EC 3.1.1.3) inhibition assay. Determination of lipid accumulation in 3T3-L1 adipocytes was evaluated with Oil Red lipid staining. Results Hydrolysates either with pepsin/pancreatin or alcalase showed strong inhibitory activity against pancreatic lipase with no statistical differences between them (IC50 = 3.21 and 1.23 mg/mL, respectively). Results from the SDS-PAGE indicate both BBPH had an average size of <15 kDa. It was possible to identify a higher number of peptide sequences with alcalase BBPH than using pepsin/pancreatin. Physical properties of identified peptides from pepsin/pancreatin were: SGNGGGGGASM, pI = 6, net charge = +1; SKPGGGSPVA pI = 10.1, net charge = +1; VELVGPK, pI = 6.9, net charge = +1; KPTTGKGALA, pI = 10.6, net charge = +1; the main reported bioactivities were DPP-IV and ACE inhibitors. BPPH inhibited 3T3-L1 adipocyte differentiation in a dose-dependent manner. Hydrolysates generated by simulated gastrointestinal digestion prevented lipid accumulation on adipocytes in basal conditions (IC50 = 1.08 mg/mL). Pepsin/pancreatin and alcalase BBPH promoted an important decrease in fat accumulation (45.28% and 12.08%, respectively) in comparison to non-treated adipocytes. Conclusions Common black bean peptides generated by either simulated gastrointestinal digestion or alcalase play an influential role in lipid metabolism. They could be considered a promising alternative to be integrated as functional ingredients into a food matrix. Funding Sources Scientific Projects Grant “Para Atender problemas Nacionales” 2016 No. 2081. CONACYT, and USDA-NIFA-HATCH project 1,014,457.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyuan Mi ◽  
Jia Liu ◽  
Xiaojing Liu ◽  
Yishan Fu ◽  
Junjie Yi ◽  
...  

The aim of the current study was to evaluate the interaction effects of myricetrin and dihydromyricetin in inhibiting α-glucosidase and pancreatic lipase at different combination ratios and concentrations and to illuminate the underlying mechanisms of their inhibitions by molecular docking analyses. Results showed that both phenolic compounds possessed good inhibitory effects toward two enzymes in a dose-dependent manner. Myricetrin demonstrated a stronger inhibition against α-glucosidase (IC50, 41.14 ± 2.52 and more than 200 μg/mL, respectively), while dihydromyricetin had a better pancreatic lipase inhibition (IC50, 244.96 ± 4.24 and 373.26 ± 21.36 μg/mL, respectively). Different interaction types were observed when myricetrin and dihydromyricetin inhibited α-glucosidase and pancreatic lipase in combination, which were closely related to the combination ratio and concentration. For α-glucosidase inhibition, synergistic effects were observed at relative low concentrations when the combination ratio of myricetrin to dihydromyricetin was set as 1 : 2, while strong synergistic effects existed at relative high concentrations for pancreatic lipase inhibition. In other combination ratios (1 : 1 or 2 : 1), additive and/or antagonistic effects occurred. Molecular docking analyses showed that myricetrin formed nine hydrogen bonds with α-glucosidase, while only three hydrogen bonds were formed between dihydromyricetin and α-glucosidase. However, these two phenolic compounds had similar hydrogen bonds and hydrophobic interactions with pancreatic lipase. The present study suggested that myricetrin and dihydromyricetin or food materials rich in these two phenolic compounds could be exploited as α-glucosidase and/or pancreatic lipase inhibitors to deal with health problems caused by excessive energy intake, and the combination ratio and concentration of these two phenolic compounds should be considered when producing new functional foods.


Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.


2020 ◽  
Vol 64 (2) ◽  
pp. 383-396
Author(s):  
Lara K. Krüger ◽  
Phong T. Tran

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.


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