Lipid Accumulation Process Research Articles

Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro

Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (Heloderma suspectum) and crotamine (Crotalus durissus terrificus) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A2 and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of C. aquilus, C. ravus, and C. scutulatus scutulatus were capable of reverting insulin resistance, enhancing glucose consumption to normal control; C. culminatus, C. molossus oaxacus, and C. polystictus diminished the lipid accumulation on adipocytes by 20%; C. aquilus, C. ravus, and C. s. salvini had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. C. aquilus, C. pyrrhus, and C. s. salvini inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from Crotalus venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that Crotalus venom peptide fractions have antioxidant and inflammatory properties in vitro models.

Single and combined effects of high-fat diet and ammonia nitrogen on oxidative stress, lipid accumulation and inflammation in liver of grass carp Ctenopharyngodon idella

The current study aims to investigate the role of high-fat diet (HFD) and ammonia nitrogen (AN) in the fatty liver disease progression in farmed fish. In the present study, grass carp were fed the normal fat diet or HFD for 4 weeks to set up the Control group, HFD group, AN group and HFD + AN group. In the AN group and HFD + AN group, grass carp were exposed to 0.52 mg/L NH3-N for the last week. The results show that HFD feeding had no effect on the growth of grass carp but AN stress significantly inhibited it. Further, the HFD feeding and AN challenge both significantly increased the level of alanine aminotransferase (ALT) and reduced the total antioxidant capacity (T-AOC) significantly. Moreover, a further aggravated liver injury appeared in HFD-fed grass carp after AN challenge, as evidenced by the significant increasing of the level of ALT, AST and malondialdehyde (MDA) and marked reducing of glutathione (GSH) and T-AOC. Moreover, the results of Oil Red O and TG contents in liver all indicate that HFD and AN challenge both promoted the lipid accumulation in grass carp liver. Corresponding to this, the results of genes and protein related to lipid metabolism reveal that AN challenge dramatically inhibited lipid hydrolysis, lipophagy and fatty acid oxidation in HFD-fed grass carp liver but the single HFD feeding or AN challenge did not have this effect. Moreover, the single HFD feeding and AN challenge both promoted fatty acid transport to the liver and lipid synthesis in grass carp liver. In summary, the HFD feeding and AN challenge both can disturb the lipid metabolism in grass carp liver. In parallel, the results of expression levels of genes and protein related to inflammation indicate that the single HFD feeding might not significantly contribute to the inflammation in grass carp liver, but the single AN challenge apparently promoted the inflammatory process. Most importantly, inflammatory progression in liver was further aggravated in the HFD-fed grass carp after AN challenge compared to grass carp with only AN stress, mostly evidenced by the increased levels of inflammatory factors (il1β, il2, TNF-α, etc.). In summary, AN challenge significantly promoted the lipid accumulation and inflammatory process in the liver of HFD-fed grass carp, which might have further aggravated liver injury.

Fatty acid metabolization and insulin regulation prevent liver injury from lipid accumulation in Himalayan marmots

Fat storage and weight gain are dominant traits for hibernating mammals. However, excessive fat accumulation may cause liver damage. Here, we explore the lipid accumulation and metabolic processes of the Himalayan marmot (Marmota himalayana), a hibernating rodent species. We find that the unsaturated fatty acid (UFA) content in food was consistent with a large increase in the body mass of Himalayan marmots. Metagenomic analysis shows that Firmicutes Bacterium CAG:110 plays a synergistic role by synthesizing UFAs, which is demonstrated by fecal transplantation experiments, indicating that the gut microbiome promotes fat storage in Himalayan marmots for hibernation. Microscopic examination results indicate that the risk of fatty liver appears at maximum weight; however, liver function is not affected. Upregulations of UFA catabolism and insulin-like growth factor binding protein genes provide an entry point for avoiding liver injury.

Improvement of obesity-induced fatty liver disease by intermittent hypoxia exposure in a murine model.

Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) in the world raises an important concern for human health. The western diet containing high fat and fructose is the risk factor for NAFLD development. Intermittent hypoxia (IH), known as the basis of obstructive sleep apnea (OSA), normally is correlated with impaired liver function. However, the role of IH in liver injury prevention has been revealed by many other studies based on the different IH paradigms. The current study, therefore, tests the impact of IH on the liver of high-fat and high-fructose diet (HFHFD) fed mice. Material and Method: Mice were exposed to IH (2min cycle, FiO2 8% for 20s, FiO2 20.9% for 100s; 12h/day) or intermittent air (FiO2 20.9%) for 15weeks, with normal diet (ND) or high-fat and high-fructose diet (HFHFD). Indices of liver injury and metabolism were measured. Results: IH causes no overt liver injury in mice fed an ND. However, HFHFD-induced lipid accumulation, lipid peroxidation, neutrophil infiltration, and apoptotic process were significantly attenuated by IH exposure. Importantly, IH exposure altered bile acids composition and shifted the hepatic bile acids towards FXR agonism, which was involved in the protection of IH against HFHFD. Conclusion: These results support that the IH pattern in our model prevents liver injury from HFHFD in experimental NAFLD.

PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.

Background & aimsTransient regeneration–associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid β‐oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism‐associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high‐fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknownMethods Park7 knockout (Park7 −/−), hepatocyte‐specific Park7 knockout (Park7 △hep) and hepatocyte‐specific Park7‐Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx)ResultsIncreased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx. Park7 −/− and Park7 △hep mice showed delayed liver regeneration and enhanced TRAS after PHx. PPARa, a key regulator of β‐oxidation, and carnitine palmitoyltransferase 1a (CPT1a), a rate‐limiting enzyme of β‐oxidation, had substantially decreased expression in the regenerating liver of Park7 △hep mice. Increased phosphatase and tensin homolog (PTEN) expression was observed in the liver of Park7 △hep mice, which might contribute to delayed liver regeneration in these mice because genomic depletion or pharmacological inhibition of PTEN restored the delayed liver regeneration by reversing the downregulation of PPARa and CPT1a and in turn accelerating the utilization of TRAS in the regenerating liver of Park7 △hep miceConclusion Park7/Dj1 is a novel regulator of PTEN‐dependent fatty acid β‐oxidation, and increasing Park7 expression might be a promising strategy to promote liver regeneration.

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

H2S is generated in the adipose tissue by cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S plays multiple roles in the regulation of various metabolic processes, including insulin resistance. H2S biosynthesis also occurs in adipocytes. Aging is known to be associated with a decline in H2S. Therefore, the question arises whether endogenous H2S deficiency may affect the process of adipocyte maturation and lipid accumulation. Among the three H2S-generating enzymes, the role of 3-MST is the least understood in adipocytes. Here we tested the effect of the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) and the H2S donor (GYY4137) on the differentiation and adipogenesis of the adipocyte-like cells 3T3-L1 in vitro. 3T3-L1 cells were differentiated into mature adipocytes in the presence of GYY4137 or HMPSNE. HMPSNE significantly enhanced lipid accumulation into the maturing adipocytes. On the other hand, suppressed lipid accumulation was observed in cells treated with the H2S donor. 3-MST inhibition increased, while H2S donation suppressed the expression of various H2S-producing enzymes during adipocyte differentiation. 3-MST knockdown also facilitated adipocytic differentiation and lipid uptake. The underlying mechanisms may involve impairment of oxidative phosphorylation and fatty acid oxidation as well as the activation of various differentiation-associated transcription factors. Thus, the 3-MST/H2S system plays a tonic role in suppressing lipid accumulation and limiting the differentiation of adipocytes. Stimulation of 3-MST activity or supplementation of H2S—which has been recently linked to various experimental therapeutic approaches during aging—may be a potential experimental approach to counteract adipogenesis.

MicroRNA Expression Profile Analysis of Chlamydomonas reinhardtii during Lipid Accumulation Process under Nitrogen Deprivation Stresses

Lipid accumulation in various microalgae has been found induced by nitrogen deprivation, and it controls many different genes expression. Yet, the underlying molecular mechanisms still remain largely unknown. MicroRNA (miRNAs) play a critical role in post-transcriptional gene regulation. In this study, miRNAs were hypothesized involved in lipid accumulation by nitrogen deprivation. A deep-sequencing platform was used to explore miRNAs-mediated responses induced by nitrogen deprivation in Chlamydomonas reinhardtii. The eukaryotic orthologous groups of proteins (KOG) function in the predicted target genes of miRNA with response to nitrogen deprivation were mainly involved in signal transduction mechanisms, including transcription, lipid transport, and metabolism. A total of 109 miRNA were predicted, including 79 known miRNA and 30 novel miRNA. A total of 29 miRNAs showed significantly differential expressions after nitrogen deprivation, and most of them were upregulated. A total of 10 miRNAs and their targeting genes might involve in lipid transport and metabolism biological process. This study first investigates nitrogen deprivation-regulated miRNAs in microalgae and broadens perspectives on miRNAs importance in microalgae lipid accumulation via nitrogen deprivation. This study provides theoretical guidance for the application of microalgae in bio-oil engineering production.

Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway.

The lipid metabolism disorder is the key role of Nonalcoholic fatty liver disease (NAFLD). Selenoprotein P plays an important role in the pathological process of lipid accumulation. Coix lacryma-jboi seed oil (CLSO) is an active component extracted from Coix lacryma-jobi seed (CLS) which has been found to be effective of reducing blood fat and antioxidative. But the effect and mechanism of CLSO on NAFLD are not clear. The aim of this study was to explore the therapeutic effect and mechanism of CLSO in the treatment of NAFLD. Our result showed that CLSO decreased the liver/body weight ratio, lowered the total cholesterol (TC) and triacylglycerol (TG), and elevated the high density lipoprotein (HDL) in serum. CLSO reduced the lipid deposition in the liver of NAFLD rats. In addition, CLSO could bring down the abnormal expression of superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, CLSO significantly declined the liver apolipoprotein E (apoE), apolipoprotein E receptor (apoER) and selenoprotein P 1 (SePP1) expression. In vivo, CLSO decreased the lipid droplets and TG level, reduced the protein expression of SePP1, apoER, phosphor-adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) in the cytoplasm of HepG2 cells induced by oleic acid and palmitic acid (OP). At the same time, lipid accumulation was observed in the Sepp1 high expression cells induced by endoplasmic reticulum (ER) activator tunicamycin (Tm). CLSO could identically reduce the protein expression of SePP1, apoER, p-AMPK in the cytoplasm of HepG2 cells induced by Tm. This result not only proved the CLSO had therapeutic effect on NAFLD, but also confirmed its mechanism associated with degrading the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) which led to the decrease of the expression SePP1/apoER2 in order to reduce lipid accumulation. The study suggests CLSO has great medicinal value in treating NAFLD besides its edibility.

Green energy from Coelastrella sp. M-60: Bio-nanoparticles mediated whole biomass transesterification for biodiesel production

Application of nanoparticles in microalgal biodiesel production comprise of nanoparticle usage for lipid accumulation, lipid extraction and transesterification process. Conventionally, microalgal biomass/oil are converted into fatty acid methyl esters (FAME) using methanol in the presence of homogeneous acid/base catalysis through transesterification. In this study, bio-nanoparticles were synthesized from bio-waste (seashell) and employed them as heterogeneous catalysts in the direct/whole-cell transesterification of wet microalgal biomass. Bio-nano CaO and bio-nano CaCO3 were characterized by Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FT-IR) analyses. Specific surface areas of bio-nano CaCO3 and bio-nano CaO were found to be 73.519 and 19.810 m2/g with an average pore size diameter of 7.141 and 2.348 nm respectively through BET analysis. FT-IR analysis of the synthesized bio-nanoparticles showed similar absorption frequencies as that of bulk counterpart with noticeable differences in absorption at some frequencies. Thus, the present study employs the as-synthesized bio-nanoparticles from waste seashell as heterogeneous catalysts for whole-cell/direct transesterification of N starved Coelastrella sp. M-60 for FAME conversion and compared with (i) conventional acid catalyst and (ii) commercial TiO2 nanocatalyst. The above mentioned direct transesterification reactions had yielded C 16:0 (7.5–22.3%) and C 18:1 (63.2–78%) as the major FAME products. Bio-nano CaCO3 and bio-nano CaO had yielded an average of 1.29 and 1.02 folds increase in FAME proportions respectively than conventional acid catalysis. Hence, this study shows the potential of bio-nanocatalysts for direct transesterifcation of Coelastrella sp. M-60 as a greener approach for biodiesel production.

Lipid Accumulation Modulation by Garcinia atroviridis Fruit Extract in 3T3-L1 Adipocyte Cells

Garcinia atroviridis contains hydroxycitric acid (HCA) that affects obesity and obesity-related diseases. This paper aims to quantify the amount of (HCA) available in the fruit extract of Garcinia atroviridis and investigate the lipid modulation properties possessed by the extract in the 3T3-L1 adipocyte cell line. High-performance liquid chromatography (HPLC) analysis was used to quantify HCA in the extract, whereas differentiated adipocytes were evaluated Oil Red O staining. The expression of PPARγ and C/EBPα was investigated using western blot, and the lipid content was confirmed using leptin ELISA assay. HPLC analysis quantified about 11.35 ± 0.55 % (w/w) of HCA in the fruit extract, with a retention time of 0.9 minutes corresponding to the standard. In the adipogenesis assay, an increased co-treatment concentration was observed and inhibited the formation of intracellular lipids. According to the western blot analysis, the treatment was found to significantly affect the expression of C/EBPα proteins solely. Meanwhile, the leptin assay finding was in agreement with the adipogenesis analysis as a decrement of leptin released was noted at increased treatment concentrations. Finally, the fruit extract enhanced the adipocyte breakdown (adipolysis) process as revealed by the glycerol concentration measured in the adipolysis assay. The findings indicated that the fruit extract of G. atroviridis played a role in the alteration of lipid accumulation processes by the intervention of proteins associated with adipogenesis and enhanced adipolysis.

Early cell-autonomous accumulation of neutral lipids during infection promotes mycobacterial growth.

Lipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process and importance of lipid accumulation, we developed methods for direct in vivo visualization and quantification of this process using the zebrafish-M. marinum larval model of infection. We find that neutral lipids accumulate cell-autonomously in mycobacterium-infected macrophages in vivo during early infection, with detectable levels of accumulation by two days post-infection. Treatment with ezetimibe, an FDA-approved drug, resulted in decreased levels of free cholesterol and neutral lipids, and a reduction of bacterial growth in vivo. The effect of ezetimibe in reducing bacterial growth was dependent on the mce4 operon, a key bacterial determinant of lipid utilization. Thus, in vivo, lipid accumulation can occur cell-autonomously at early timepoints of mycobacterial infection, and limitation of this process results in decreased bacterial burden.

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism.

The dysregulation of hepatic lipid metabolism is one of the hallmarks in many liver diseases including alcoholic liver diseases (ALD) and non-alcoholic fatty liver diseases (NAFLD). Hepatic inflammation, lipoperoxidative stress as well as the imbalance between lipid availability and lipid disposal, are direct causes of liver steatosis. The application of herbal medicines with anti-oxidative stress and lipid-balancing properties has been extensively attempted as pharmaceutical intervention for liver disorders in experimental and clinical studies. Although the molecular mechanisms underlying their hepatoprotective effects warrant further exploration, increasing evidence demonstrated that many herbal medicines are involved in regulating lipid accumulation processes including hepatic lipolytic and lipogenic pathways, such as mitochondrial and peroxisomal β-oxidation, the secretion of very low density lipoprotein (VLDL), the non-esterified fatty acid (NEFA) uptake, and some vital hepatic lipogenic enzymes. Therefore, in this review, the pathways or crucial mediators participated in the dysregulation of hepatic lipid metabolism are systematically summarized, followed by the current evidences and advances in the positive impacts of herbal medicines and natural products on the lipid metabolism pathways are detailed. Furthermore, several herbal formulas, herbs or herbal derivatives, such as Erchen Dection, Danshen, resveratrol, and berberine, which have been extensively studied for their promising potential in mediating lipid metabolism, are particularly highlighted in this review.

In situ and non-destructive detection of the lipid concentration of Scenedesmus obliquus using hyperspectral imaging technique

Microalgae can be used as a raw material for biodiesel production. Monitoring the lipid accumulation process of microalgae is crucial for optimizing the microalgae culture environment and the breeding of microalgae species with a high yield of lipid. Current methods for the detection of the lipid accumulation of microalgae are tedious and require trained professionals. Thus, a fast visual and intuitive approach for the detection of the lipid concentration of microalgae with a living status is desirable for microalgae culture and bioprocess control. In this study, a fast and nondestructive method based on hyperspectral imaging (HSI) was proposed to obtain the concentration and distribution of microalgae lipids from liquid suspension culture. Several data preprocessing, regression and model development methods were tested. Savitzky-Golay data smoothing followed by a competitive adaptive reweighted sampling in a multiple linear regression model performed the best. Finally, a chemical map was provided to visualize the lipid distribution of microalgae in a suspension. The distribution map of microalgae lipids showed a dynamic process of lipid accumulation, which could be useful for the investigation of the mechanism of lipid accumulation in microalgae. Hyperspectral imaging is a promising approach to inspect the lipid concentration of microalgae in an intuitive way, which can be widely used for the screening of strains and monitoring the lipid production in microalgae industries.

Expression of the Biologically Active Insulin Analog SCI-57 in Nicotiana Benthamiana.

Diabetes mellitus is a growing problem worldwide; however, only 23% of low-income countries have access to insulin, and ironically it costs higher in such countries than high-income ones. Therefore, new strategies for insulin and insulin analogs production are urgently required to improve low-cost access to therapeutic products, so as to contain the diabetes epidemic. SCI-57 is an insulin analog with a greater affinity for the insulin receptor and lower thermal degradation than native insulin. It also shows native mitogenicity and insulin-like biological activity. In this work, SCI-57 was transiently expressed in the Nicotiana benthamiana (Nb) plant, and we also evaluated some of its relevant biological effects. An expression plasmid was engineered to translate an N-terminal ubiquitin and C-terminal endoplasmic reticulum-targeting signal KDEL, in order to increase protein expression and stability. Likewise, the effect of co-expression of influenza M2 ion channel (M2) on the expression of insulin analog SCI-57 (SCI-57/M2) was evaluated. Although using M2 increases yield, it tends to alter the SCI-57 amino acid sequence, possibly promoting the formation of oligomers. Purification of SCI-57 was achieved by FPLC cation exchange and ultrafiltration of N. benthamiana leaf extract (NLE). SCI-57 exerts its anti-diabetic properties by stimulating glucose uptake in adipocytes, without affecting the lipid accumulation process. Expression of the insulin analog in agroinfiltrated plants was confirmed by SDS-PAGE, RP-HPLC, and MS. Proteome changes related to the expression of heterologous proteins on N. benthamiana were not observed; up-regulated proteins were related to the agroinfiltration process. Our results demonstrate the potential for producing a biologically active insulin analog, SCI-57, by transient expression in Nb.

Tributyltin chloride (TBT) induces RXRA down-regulation and lipid accumulation in human liver cells.

A subset of environmental chemicals acts as “obesogens” as they increase adipose mass and lipid content in livers of treated rodents. One of the most studied class of obesogens are the tin-containing chemicals that have as a central moiety tributyltin (TBT), which bind and activate two nuclear hormone receptors, Peroxisome Proliferator Activated Receptor Gamma (PPARG) and Retinoid X Receptor Alpha (RXRA), at nanomolar concentrations. Here, we have tested whether TBT chloride at such concentrations may affect the neutral lipid level in two cell line models of human liver. Indeed, using high content image analysis (HCA), TBT significantly increased neutral lipid content in a time- and concentration-dependent manner. Consistent with the observed increased lipid accumulation, RNA fluorescence in situ hybridization (RNA FISH) and RT-qPCR experiments revealed that TBT enhanced the steady-state mRNA levels of two key genes for de novo lipogenesis, the transcription factor SREBF1 and its downstream enzymatic target, FASN. Importantly, pre-treatment of cells with 2-deoxy-D-glucose reduced TBT-mediated lipid accumulation, thereby suggesting a role for active glycolysis during the process of lipid accumulation. As other RXRA binding ligands can promote RXRA protein turnover via the 26S proteasome, TBT was tested for such an effect in the two liver cell lines. We found that TBT, in a time- and dose-dependent manner, significantly reduced steady-state RXRA levels in a proteasome-dependent manner. While TBT promotes both RXRA protein turnover and lipid accumulation, we found no correlation between these two events at the single cell level, thereby suggesting an additional mechanism may be involved in TBT promotion of lipid accumulation, such as glycolysis.

Soy Isoflavones Ameliorate Fatty Acid Metabolism of Visceral Adipose Tissue by Increasing the AMPK Activity in Male Rats with Diet-Induced Obesity (DIO).

Soy isoflavones are natural active ingredients of soy plants that are beneficial to many metabolic diseases, especially obesity. Many studies have reported that obesity is closely related to visceral fatty acid metabolism, but the effect has not been well defined. In this study, we show that soy isoflavones improve visceral fatty acid metabolism in diet-induced obese male rats, which was indicated by reduced body weight and visceral fat cell area, as well as suppressed visceral fat synthesis and accelerated fat hydrolysis. We also found that common components of soy isoflavones, daidzein and genistein, were able to inhibit the lipid accumulation process in 3T3-L1 cells. Moreover, we showed that soy isoflavones can promote on AMP-activated protein kinase (AMPK) activity both in vivo and in vitro, which may be implicated in lipid metabolism regulation of soy isoflavones. Our study demonstrates the potential of soy isoflavones as a mechanism for regulating lipid homeostasis in visceral adipose tissue, proven to be beneficial for obesity treatment.

NUTRIGENOMICS AS A TOOL IN THE PREVENTION OF LIPOTOXICITY: THE CASE OF SOY PROTEIN.

Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.

Metabolic traits specific for lipid-overproducing strain of Mucor circinelloides WJ11 identified by genome-scale modeling approach.

The genome-scale metabolic model of a lipid-overproducing strain of Mucor circinelloides WJ11 was developed. The model (iNI1159) contained 1,159 genes, 648 EC numbers, 1,537 metabolites, and 1,355 metabolic reactions, which were localized in different compartments of the cell. Using flux balance analysis (FBA), the iNI1159 model was validated by predicting the specific growth rate. The metabolic traits investigated by phenotypic phase plane analysis (PhPP) showed a relationship between the nutrient uptake rate, cell growth, and the triacylglycerol production rate, demonstrating the strength of the model. A putative set of metabolic reactions affecting the lipid-accumulation process was identified when the metabolic flux distributions under nitrogen-limited conditions were altered by performing fast flux variability analysis (fastFVA) and relative flux change. Comparative analysis of the metabolic models of the lipid-overproducing strain WJ11 (iNI1159) and the reference strain CBS277.49 (iWV1213) using both fastFVA and coordinate hit-and-run with rounding (CHRR) showed that the flux distributions between these two models were significantly different. Notably, a higher flux distribution through lipid metabolisms such as lanosterol, zymosterol, glycerolipid and fatty acids biosynthesis in iNI1159 was observed, leading to an increased lipid production when compared to iWV1213. In contrast, iWV1213 exhibited a higher flux distribution across carbohydrate and amino acid metabolisms and thus generated a high flux for biomass production. This study demonstrated that iNI1159 is an effective predictive tool for the pathway engineering of oleaginous strains for the production of diversified oleochemicals with industrial relevance.

Resistin up-regulates LPL expression through the PPARγ-dependent PI3K/AKT signaling pathway impacting lipid accumulation in RAW264.7 macrophages

Resistin is a cysteine-rich cytokine, which has been indicated as a mediator of insulin resistance and inflammation. Previous studies demonstrated that lipoprotein lipase (LPL) was an important enzyme that could mediate lipid accumulation in macrophages. Additionally, the intracellular molecules phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/peroxisome proliferator-activated receptor (PPARγ) were supposed to be involved in the lipid accumulation process in cells. However, it remains unclear whether resistin was correlated with the dysregulation of lipid metabolism in macrophages. The present study investigated that resistin could up-regulate the expression of LPL and increase the contents of intracellular triglyceride (TG) and total cholesterol (TC) in RAW264.7 macrophages. In addition, intracellular molecules PI3K, AKT and PPARγ were significantly up-regulated and activated in resitin-stimulated RAW264.7 macrophages (P < 0.05). In contrast, the effects of resistin on RAW264.7 macrophages could be abrogated by specific inhibitors for LPL (LPL-siRNA) and PI3K/AKT signaling pathway (LY294002). All together, this study demonstrated that resistin could up-regulate the expression of LPL and induce lipid accumulation in RAW264.7 macrophages. More importantly, the PPARγ-dependent PI3K/AKT signaling pathway was relevant to the lipid accumulation process in resistin-stimulated macrophages.

Production of Fame (Fatty Acid Methyl Esters) From Waste Carbon Sources by Aspergillus Niger

Single cell organism based oil from oleaginous microorganisms has involved the attention because of its significance in the production of biodiesel as well as reducing pollution and waste. The fungi Aspergillus niger was isolated from the soil and used for FAME extraction. Different waste containing carbon source on biomass and lipid production of Aspergillus niger were used. Optimization of FAME production from Aspergillus niger using waste was studied. Different low cost and easily available carbon based feedstock substrate such as Orange peel, Potato peel, Sugarcane bagasse and Rice husk was characterized as carbon source. These feedstocks were used for the culturing of Aspergillus niger. There was a significant difference in the lipid accumulation process as related to these carbon sources. The FAME produced from the fungal lipid contains long chain fatty acids and higher number of saturated fatty acids and so it has the efficiency of acquiring high fuel and lubricating properties. This process leads to the integrated process for production of alternative fuel with integration of waste management.