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Takahito Otani, Miho Matsuda, Akiko Mizokami, Norio Kitagawa, Hiroshi Takeuchi, Eijiro Jimi, Tetsuichiro Inai, Masato Hirata
The uncarboxylated form of osteocalcin (GluOC) regulates glucose and lipid metabolism in mice. We previously showed that low-dose (≤10 ng/ml) GluOC induces the expression of adiponectin and peroxisome proliferator-activated receptor γ (PPARγ) via a cAMP-PKA-ERK-CREB signaling pathway in 3T3-L1 adipocytes. We also noticed that high-dose (≥20 ng/ml) GluOC inhibits the expression of adiponectin and PPARγ in these cells. We have here explored the mechanism underlying these effects of high-dose GluOC...
December 13, 2018: Cell Death & Disease
Kuang-Tzu Huang, Li-Wen Hsu, Kuang-Den Chen, Chao-Pin Kung, Shigeru Goto, Chao-Long Chen
Adipogenesis is a tightly regulated cellular process that involves the action of multiple signaling pathways. Characterization of regulators that are associated with adipose development is crucial to understanding the mechanisms underlying obesity and other metabolic disorders. Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that was first described as a neurotrophic factor. The role of PEDF in lipid metabolism was established when adipose triglyceride lipase (ATGL), a major triglyceride hydrolase, was characterized as its binding partner...
December 11, 2018: International Journal of Molecular Sciences
Mi-Kyoung Kim, Hyun-Joo Park, Yeon Kim, Soo-Kyung Bae, Hyung Joon Kim, Moon-Kyoung Bae
Gastrin-releasing peptide (GRP), a member of bombesin-like peptides, and its receptor (GRP-R) play an important role in various physiological and pathological conditions. In this work, we investigated the role of GRP-R on adipogenesis in 3T3-L1 adipocytes. The expression of GRP-R was significantly increased during the adipocyte differentiation of 3T3-L1 cells. The inhibition of GRP-R by the antagonist RC-3095 affected adipogenesis in 3T3-L1 cells, which reduced lipid accumulation and regulated the expression of adipogenic genes...
December 10, 2018: International Journal of Molecular Sciences
Christoph Schmid, Claudia Ghirlanda, Cornelia Zwimpfer, Oliver Tschopp, Richard A Zuellig, Markus Niessen
Cystatin C (CysC) is a marker for estimation of glomerular filtration rate (GFR). CysC levels may depend not only on clearance/GFR but possibly also on changes in production. Our studies on tissue distribution of CysC protein in mice showed that adipose tissue expresses significant amounts of CysC, suggesting that adipocytes could contribute to circulating CysC levels in vivo. As growth hormone (GH) and triiodothyronine (T3 ) increase both GFR and CysC (increased in acromegaly and hyperthyroidism) in vivo, we studied whether they could increase CysC production in 3T3-L1 adipocytes in vitro...
December 10, 2018: Molecular and Cellular Endocrinology
Andreas Schmid, Jutta Schlegel, Miriam Thomalla, Thomas Karrasch, Andreas Schäffler
BACKGROUND AND AIM: Bile acids (BA) are increasingly recognized as pleiotropic and hormone-like signaling molecules with metabolic and endocrine functions. However, the role of BA in white adipocyte physiology remains somewhat obscure. It was the aim to investigate the BA receptors (FXR, TGR5) and FGFR1 (Fibroblast growth factor receptor 1) as well as Bsep (bile salt export pump) in white adipocytes and in murine and human adipose tissue (AT) and to investigate effects of different BA species in adipocyte physiology...
December 10, 2018: Molecular and Cellular Endocrinology
Meghan J Bloom, Sachit D Saksena, George P Swain, Marcelo S Behar, Thomas E Yankeelov, Anna G Sorace
Small molecule approaches targeting the nuclear factor kappa B (NF-kB) pathway, a regulator of inflammation, have thus far proven unsuccessful in the clinic in part due to the complex pleiotropic nature of this network. Downstream effects depend on multiple factors including stimulus-specific temporal patterns of NF-kB activity. Despite considerable advances, genome-level impact of changes in temporal NF-kB activity caused by inhibitors and their stimulus dependency remains unexplored. This study evaluates the effects of pathway inhibitors on early NF-κB activity and downstream gene transcription...
December 10, 2018: Cellular Signalling
D Torres-Villarreal, A Camacho, H Castro, R Ortiz-Lopez, A L de la Garza
Kaempferol is a natural flavonoid widely found in fruits, vegetables, and tea. Kaempferol possesses beneficial biological properties such as anti-inflammatory and antioxidant activities. Positive energy balance during obesity correlates with a pro-inflammatory chronic state. In this context, we hypothesized that kaempferol might promote anti-obesity effects by modulating adipogenesis and lipolytic pathways. Adipocyte viability at 24, 48, and 72 h was measured by an ATP-based assay. Pre-adipocytes (day 0) or mature adipocytes (day 12) were treated with 60 μM kaempferol until day 21 to evaluate its potential anti-adipogenic and lipolytic effect, respectively...
December 12, 2018: Journal of Physiology and Biochemistry
Menglin Fan, Yanan Li, Chunhua Yao, Xiufeng Liu, Jihua Liu, Boyang Yu
Artemisinins have been reported to have diverse functions, such as antimalaria, anticancer, anti-inflammation, and immunoregulation activities. DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative possessing potent immunosuppressive properties, was synthesized in our previous study. Collagen-induced arthritis (CIA) in DBA/1 mice and inflammatory model in NIH-3T3 cells were established to evaluate the effect of DC32 on RA and discover the underlying mechanisms. The results showed that DC32 could markedly alleviate footpad inflammation, reduce cartilage degradation, activate the Nrf2/HO-1 signaling pathway, and increase the transcription of p62 in DBA/1 mice with CIA...
2018: Frontiers in Immunology
Yeon-Seop Jung, Hyo-Seon Lee, Hye-Rin Cho, Keuk-Jun Kim, Joung-Hee Kim, Stephen Safe, Syng-Ook Lee
BACKGROUND: Suppression of adipogenesis has been considered as a potential target for the prevention and treatment of obesity and associated metabolic disorders, and the nuclear receptor 4A1 (NR4A1/Nur77) and AMPKα are known to play important roles during early and intermediate stages of adipogenesis. Therefore, we hypothesized that dual targeting Nur77 and AMPKα would show strong inhibitory effect on adipogenesis. METHODS: We screened a herbal medicine-based small molecule library to identify novel natural compounds dual targeting Nur77 and AMPKα, and the antiadipogenic effects and mechanisms of action of a "hit" compound were studied in 3T3-L1 cells...
December 11, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Eleanor Cave, Nigel J Crowther
The 3T3-L1 murine preadipocyte cell line is a commonly used tool for analysis of the subcellular pathways involved in preadipocytic cell differentiation (a process also commonly known as adipogenesis). The major characteristic of adipogenesis is the intracellular accumulation of membrane-bound lipid droplets. Here, we describe methods used for the culture and transformation of these preadipocytes into mature adipocytes and quantification of intracellular lipid accumulation using the lipid specific dye, Oil Red O...
2019: Methods in Molecular Biology
Wen-Chung Huang, Ya-Ling Chen, Hui-Chia Liu, Shu-Ju Wu, Chian-Jiun Liou
Ginkgolide C, isolated from Ginkgo biloba , is a diterpene lactone that has multiple biological functions and can improve Alzheimer disease and platelet aggregation. Ginkgolide C also inhibits adipogenesis in 3T3-L1 adipocytes. The present study evaluated whether ginkgolide C reduced lipid accumulation and regulated the molecular mechanism of lipogenesis in oleic acid-induced HepG2 hepatocytes. HepG2 cells were treated with 0.5 mM oleic acid for 48 h to induce a fatty liver cell model. Then, the cells were exposed to various concentrations of ginkgolide C for 24 h...
December 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
María-Luisa Nueda, María-Julia González-Gómez, María-Milagros Rodríguez-Cano, Eva-María Monsalve, María José M Díaz-Guerra, Beatriz Sánchez-Solana, Jorge Laborda, Victoriano Baladrón
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
December 7, 2018: Scientific Reports
Florentina Negoita, Johanna Säll, Björn Morén, Karin Stenkula, Olga Göransson
Dysregulation of autophagy has been observed in obesity and type 2 diabetes. Salt-inducible kinase 2 (SIK2), a member of the AMPK-related kinase family, is downregulated in adipocytes from obese or insulin resistant individuals and was previously demonstrated to regulate autophagy in cancer and normal cell lines. The aim of this study was thus to investigate a potential role of SIK2 in the regulation of adipocyte autophagy. To do so, SIK2 siRNA silencing or SIKs pharmacological inhibition of SIK2 was employed in murine differentiated 3T3-L1 adipocytes and autophagic flux was monitored...
December 6, 2018: Biochemical and Biophysical Research Communications
Mei Ge, Rui Guo, Hai-Xia Lou, Wen Zhang
BACKGROUND: Cordyceps sinensis has been used for centuries in China as one of the most valued herbal medicine and tonic food. Paecilomyces hepiali, a fungal strain isolated from natural C. sinensis, has been used widely as a substitute of C. sinensis in medicine and health food. P. hepiali has been reported to have various pharmaceutical benefits, including triglyceride-lowing activity. However, its effects on triglyceride metabolism in adipocytes remain unknown. The purpose of the present study was to evaluate the effect of P...
December 7, 2018: BMC Complementary and Alternative Medicine
Ann H Rosendahl, Malin Bergqvist, Barbara Lettiero, Siker Kimbung, Signe Borgquist
The global increase in overweight and obesity rates represent pressing public health concerns associated with severe comorbidities, amongst a rising incidence and impaired outcome of breast cancer. Yet, biological explanations for how obesity affects breast cancer are incompletely mapped. Herein, the joint impact by differentiated 3T3-L1 adipocytes and obesity-related metabolic conditions on breast cancer cells was evaluated in vitro and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines ( n = 47) and primary breast tumors ( n = 1,881), where associations with survival outcomes were investigated...
2018: Frontiers in Endocrinology
Muhammad Imran Khan, Jin Hyuk Shin, Tai Sun Shin, Min Yong Kim, Nam Jun Cho, Jong Deog Kim
Cornus kousa the Korean dogwood has been traditionally used in East Asia as therapeutic traditional medicine however biological activities of Cornus kousa have not been investigated previously. The aim of the present study was to evaluate anti-obesity activities coupled with anti-angiogenic activities of anthocyanins rich fraction of ethanolic leaf extract of Cornus kousa (ELECk) in HUVECs and 3T3- L1 cells. Dried plants leaves were extracted with 70% ethanol and anthocyanin fraction (AnT Fr) was obtained by eluting the ethanolic extract through non-polar macroporous resin and further purification by HPLC...
2018: PloS One
Anuradha A Shastri, Vijay Hegde, Swetha Peddibhotla, Zahra Feizy, Nikhil V Dhurandhar
BACKGROUND: Type 2 diabetes is often linked with impaired proximal insulin signaling. Hence, a therapeutic agent that enhances cellular glucose uptake without requiring proximal insulin signaling would be desirable for improving glycemic control. The E4orf1 peptide (E4) derived from human adenovirus 36 (Ad36) promotes cellular glucose uptake in vitro and in vivo, independent of insulin. E4 bypasses a part of insulin signaling to upregulate cellular glucose uptake. We tested the hypothesis that E4 requires the distal but not proximal insulin signaling to enhance cellular glucose disposal...
2018: PloS One
Maria Yousuf, Nimra Naveed Shaikh, Zaheer Ul-Haq, M Iqbal Choudhary
Identification of hotspot drug-receptor interactions through in-silico prediction methods (Pharmacophore mapping, virtual screening, 3DQSAR, etc), is considered as a key approach in drug designing and development process. In the current design study, advanced in-silico based computational techniques were used for the identification of lead-like molecules against the targeted receptor β-glucuronidase. The binding pattern of a potent inhibitor in the ligand-receptor X-ray co-crystallize complex was used to identify and extract the structure-base Pharmacophore features...
2018: PloS One
Hwa-Jin Kim, Mi-Kyoung You, Young-Hyun Lee, Hyun-Jung Kim, Deepak Adhikari, Hyeon-A Kim
BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at 4℃ (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining...
December 2018: Nutrition Research and Practice
Jae-Kyo Jeong, Ju-Hee Lee, Sung-Wook Kim, Jeong-Min Hong, Jae-Won Seol, Sang-Youel Park
The role of autophagy modulation in adipogenic differentiation and the possible autophagy modulators targeting adipogenesis remain unclear. In this study, we investigated whether normal cellular prion protein (PrP<C>) is involved in the modulation of autophagy and affects adipogenic differentiation in vivo and in vitro. Surprisingly, autophagy flux signals were activated in the adipose tissue of prion protein-deficient mice and PrP<C>-deleted 3T3-L1 adipocytes. The activation of autophagy flux mediated by PrP<C> deletion was confirmed in the adipose tissue via transmission electron microscopy...
December 1, 2018: Molecular and Cellular Endocrinology
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