Accumulation Of Lipid Content Research Articles

The interplay of transcriptional coregulator NUPR1 with SREBP1 promotes hepatocellular carcinoma progression via upregulation of lipogenesis

Nuclear protein 1 (NUPR1) is a transcriptional coregulator that has been implicated in the development of various cancer types. In addition, de novo fatty acid synthesis plays a pivotal role in hepatocellular carcinoma (HCC) development. However, little is currently known on the role of NUPR1 in hepatocellular carcinoma. In this study, bioinformatics analysis was conducted to analyze the expression level, prognosis value and enriched pathways of NUPR1 in Liver Hepatocellular Carcinoma (LIHC). We found that NUPR1 was significantly upregulated in human hepatocellular carcinoma cells compared with normal hepatocytes from LIHC patients in TCGA cohorts and our patients. Kaplan–Meier analysis and COX proportional hazard progression model showed that high expression of NUPR1 was correlated with a poor prognosis of LIHC patients. CCK-8, EdU and colony formation assays were performed to explore the effect of NUPR1 on the proliferation of HCC cells, then wound healing and transwell migration assays were performed to evaluate the effects of NUPR1 on cell migration. Furthermore, subcutaneous xenograft models were established to study tumor growth. Results showed that NUPR1 overexpression correlated with a highly proliferative and aggressive phenotype. In addition, NUPR1 knockdown significantly inhibited hepatocellular carcinoma cell proliferation and migration in vitro and hindered tumorigenesis in vivo. Mechanistically, endogenous NUPR1 could interact with sterol regulatory element binding protein 1 (SREBP1) and upregulated lipogenic gene expression of fatty acid synthase (FASN), resulting in the accumulation of lipid content. Moreover, pharmacological or genetic blockade of the NUPR1-SREBP1/FASN pathway enhanced anticancer activity in vitro and in vivo. Overall, we identified a novel function of NUPR1 in regulating hepatocellular carcinoma progression via modulation of SREBP1-mediated de novo lipogenesis. Targeting NUPR1-SREBP1/FASN pathway may be a therapeutic alternative for hepatocellular carcinoma.

Anti-lipid droplets accumulation effect of Annona montana (mountain soursop) leaves extract on differentiation of preadipocytes.

The Annona genus is a member of Annonaceae, one of the largest families of plants across tropical and subtropical regions. This family has been used in several ethnomedicinal practices to treat a multitude of human diseases. However, the molecular mechanism underlying its effect on the lipid droplet formation and on the expression of adipogenic markers of this plant remain to be investigated. In this study, we examined whether the extracts from the aerial part of Annona montana affect in vitro differentiation of preadipocytes. For our investigations, both mouse embryo fibroblast 3T3-L1 and normal human primary subcutaneous preadipocytes were incubated with Annona montana extracts (-and its subfractions-) and then analyzed on preadipocyte differentiation, lipid content, lipid droplet size and number, the expression of adipogenic-specific transcriptional factors, as well as cell survival. From our examinations, we found the Annona montana ethyl acetate extract to exhibit a potent inhibitory effect on adipogenesis, without affecting cell survival, in a dose-dependent manner. Such inhibitory effects included a significant decrease in the accumulation of lipid content by both a dramatic reduction of size and number of lipid droplets. This extract strongly attenuated the expression of PPARγ and HMGB2. It also inhibited the expression of CEBPα, FAS, and Akt without influencing Erk1/2 activities. Our findings suggest that specifically, the Annona montana ethyl acetate extract has a prominent inhibitory effect in cellular pathways of adipocyte differentiation by modulating specific gene expression, which is known to perform a pivotal role during adipogenesis.

Anti-obesity effect of Melandrium firmum Rohrbach extract in 3T3-L1 cells and high-fat diet-induced obese C57BL/6N mice.

In this study, we first investigated the influence of Melandrium firmum Rohrbach (MF) on the accumulation of lipid content in 3T3‐L1 cells and in vitro results showed that MF extraction suppressed the differentiation of 3T3‐L1 pre‐adipocytes in a concentration‐dependent manner without showing cytotoxicity. Hence, we studied the effects of MF on preventing obesity in C57BL/6N mice. The results showed that MF decreased food efficiency ratio, body weight, epididymal adipose and hepatic tissue weight, hepatic lipid metabolites, and triacylglycerol and cholesterol serum levels, when compared with the high‐fat diet group. Moreover, MF significantly inhibited the expression of genes related to adipogenesis, such as PPAR‐γ, C/EBP‐α, and aP2, and those related to lipogenesis, such as SREBP‐1c, FAS, SCD‐1, and CD36 in epididymal adipose and liver tissues. These anti‐adipogenic and anti‐lipogenic effects of MF suggest that it could be used as a food including potential functional ingredient to prevent high‐fat diet‐induced obesity.

Effects of Light-emitting Diodes (LEDs) on the Accumulation of Lipid Content in Microalgae

Microalgae is a popular condidate for the sustainable biodiesel due to its high growth rate and lipid content. This paper reviewed the effects of light conditions, including light intensity, photoperiod and spectrum on the lipid accumulation in microalgae and selects the spectrum as the variable. In this paper, the effects of different light emitting diodes (LEDs) spectra such as red, blue and white on the lipid accumulation in two microalgae species were discussed. The results showed that the total lipid content was the highest (13.76% and 31.18% of dry cell weight) in the two microalgae species, Ankistrodesmus falcatus and Chlorella vulgaris, cultured under blue light. The fatty acid methyl esters (FAME) composition was significantly influenced by the light spectrum

Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice.

Valeriana dageletiana Nakai ex F. Maek (VD) has been used as traditional medicine for the treatment of restlessness and sleeping disorders. However, it is still unclear whether obesity in mice can be altered by diet supplementation with VD. In this study, we first investigated the influences of VD on the accumulation of lipid content in 3T3-L1 cells; and the results showed that the above-ground VD extracts (VDAE) suppressed the differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner without cytotoxicity. Thus, the effects of VDAE on preventing obesity were then studied in the C57BL/6N mice for 10 weeks (n = 6): normal-fat diet, high-fat diet (HFD), HFD supplemented with 1% (10 g/kg) Garcinia combogia extract (positive control), and HFD supplemented with 1% (10 g/kg) VDAE. The results showed that VDAE reduced food efficiency ratio, body weight, epididymal adipose and hepatic tissue weight, hepatic lipid metabolites, and triacylglycerol and cholesterol serum levels compared to the high-fat diet group. Moreover, VD significantly inhibited the expression of adipogenic genes, such as PPAR-γ, C/EBP-α, and aP2, and lipogenic genes, such as SREBP-1c, FAS, SCD-1, and CD36, in epididymal adipose tissue and hepatic tissue. These findings indicate anti-adipogenic and anti-lipogenic effects of VDAE and suggest that it could be a potent functional food ingredient for the prevention of high-fat diet-induced obesity.

Effects of light-emitting diodes (LEDs) on the accumulation of lipid content using a two-phase culture process with three microalgae

Conditions of light-emitting diode (LED) wavelength, light intensity, nitrate concentration, and time of exposure to green LED light stress in a two-phase culture were optimized for lipid production with three species of microalgae. Among the three microalgae, Nannochloropsis oculata showed the highest specific growth rate (μmax) of 0.037h−1 and the lowest saturation constant (Ks) of 1.32mg/L. The highest lipid contents of the three microalgae in the second phase under green LED light stress were 52.0% (w/w) for Nannochloropsis salina at 2days, 53.0% (w/w) for Nannochloropsis oceanica at 2days, and 56.0% for N. oculata at 2days. Fatty acid analysis of the microalgae showed that 85–87% (w/w) of total fatty acids from N. salina, N. oceanica, and N. oculata consisted of palmitic acid (C16:0) and oleic acid (C18:1).

Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes

6-Gingerol has been reported to inhibit adipogenesis and lipid content accumulation. However, the mechanism of its anti-adipogenic effect remains unclear. Our aim is to investigate the molecular mechanism of the anti-adipogenic effect of 6-gingerol. The lipid content in adipocytes was measured by Oil Red O staining and cell viability was analyzed by MTT assay. The extent of suppression of differentiation by 6-gingerol was characterized by measuring the triglyceride content and GPDH activity. The regulation of adipogenic markers and the components of the Wnt/β-catenin pathway were analyzed by real-time PCR and Western blotting. The nuclear location of β-catenin was identified using immunofluorescence assay. Small interfering RNA transfection was conducted to elucidate the crucial role of β-catenin in anti-adipogenic effect of 6-gingerol. Our results showed that 6-gingerol inhibited the adipogenesis and lowered the mRNA expression levels of transcription factors and the key lipogenic enzymes in 3T3-L1 cells. The effect of 6-gingerol on adipogenic differentiation was accompanied by stimulating the activation of the Wnt/β-catenin signaling. In addition, we found that 6-gingerol induced phosphorylations of glycogen synthase kinase-3β(GSK-3β), and promoted the nuclear accumulation of β-catenin. Importantly, the inhibitory effect of 6-gingerol on adipogenic differentiation was reversed after the siRNA knockdown of β-catenin was added. Our findings demonstrated that 6-gingerol inhibits the adipogenic differentiation of 3T3-L1 cells through activating the Wnt/β-catenin signaling pathway.

The effect of dehydroleucodine in adipocyte differentiation

Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric cytoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes. The addition of DhL significantly inhibited the differentiation of 3T3-L1 preadipocytes along with a significant decrease in the accumulation of lipid content by a dramatic downregulation of the expression of adipogenic-specific transcriptional factors PPARγ and C-EBPα. However, phosphorylation of AMPKα, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we also found that 11,13-dihydrodehydroleucodine, a derivative of DhL with inactivated α-methylene-γ-lactone function, also inhibited the differentiation of 3T3-L1 preadipocytes. Taken together, these data suggest that DhL has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis.

Pathological mechanisms and dose dependency of erythrocyte-induced vulnerability of atherosclerotic plaques

To test our hypothesis that erythrocytes may induce plaque vulnerability and investigate the mechanism involved, we established a novel model of intraplaque hemorrhage in 56 New Zealand white rabbits with established plaques. Three distinct abdominal aortic plaques with similar thickness were identified in each rabbit with use of intravascular ultrasound (IVUS) imaging. Rabbits were equally divided into 4 groups depending on dosage of treatment; with the guidance of IVUS, one of the three plaques from each rabbit was injected from adventitia with autologous erythrocytes (RBC) or cholesterol (CH) for the following groups: RBC, 50 μL or 100 μL, and CH, 50 μL or 100 μL. One of the other two plaques in each rabbit received an equal volume of normal saline (NS) and one received no injection. Plaques in the 100 μL RBC group had a higher plaque rupture rate than its respective NS or blank controls plaques (57.1% vs. 14.3% or 14.3%, P < 0.05). Plaques from the RBC or cholesterol groups showed, dose-dependently, more macrophage infiltration, more superoxide and lipid content, thinner plaque fibrous cap, higher mRNA level of MCP-1, IL-1 or IFN-gamma and higher vulnerability index than controls, especially in the RBC group. Thus, erythrocyte treatment can dose-dependently induce the vulnerability of plaques. Accumulation of lipid content and augmentation of oxidative stress and inflammation in the plaques are the probable pathological mechanisms involved.