Expression Of Lipid Metabolism Genes Research Articles

Choline Alleviates Disorders of Lipid Metabolism in Hybrid Grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) Caused by High-Lipid Diet

This study was conducted to evaluate the effect of dietary choline levels on growth performance, liver histology, lipid metabolism and related gene expression of hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) fed high-lipid diets. The fish (initial body weight 6.86 ± 0.01 g ) were fed diets containing different choline levels (0, 5, 10, 15, and 20 g/kg, named D1, D2, D3, D4, and D5, respectively) for 8 weeks. The results shows that (a) dietary choline levels had no significant effect on the final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) compared with the control group ( P > 0.05 ); (b) with the increase in choline levels, triglyceride (TG), total cholesterol (TC), lipoprotein lipase (LDL), and high-density lipoprotein (HDL) of serum, all showed a tendency to increase and then decrease, and the maximum values were obtained in the D4 group ( P < 0.05 ); (c) TG and TC in the liver showed a tendency to decrease first and then increase with the dietary choline levels and reached the minimum value in D3 and D4 groups, respectively ( P < 0.05 ); (d) with increased choline levels, hepatic lipase (HL), lipoprotein lipase (LPL), adipose triglyceride lipase (ATGL), and fatty acid synthetase (FAS) in the liver all showed a tendency to increase and then decrease, and the maximum values were obtained in the D4 group, except ATGL that the maximum value was obtained in the D3 group ( P < 0.05 ); (e) oil red staining showed that dietary choline significantly reduced hepatic lipid deposition; (f) choline supplementation significantly upregulated the expression of lipolytic genes lipoprotein lipase (lpl), hormone-sensitive lipase (hsl), and peroxisome proliferator-activated receptor α (pparα) and inhibited the expression of lipid synthesis genes fatty acid synthetase (fas), acetyl-CoA carboxylase α (accα), and peroxisome proliferator-activated receptor γ (pparγ). In summary, choline can promote lipid metabolism of hybrid grouper by regulating lipid metabolism-related enzyme activity and gene expression and mitigating the negative effects of high-lipid diets.

Exercise increases the expression of glucose transport and lipid metabolism genes at optimum level time point 6 hours post exercise in rat skeletal muscle

AimType 2 diabetes constitutes more than 90% of all diabetic cases and is characterized by persistent increase in glucose level in the blood (hyperglycemia) as well as lipid and protein metabolic disorders that may induce insulin resistance. Increased lipid levels induce type 2 diabetes by interfering with the insulin‐signaling pathway responsible for glucose transport. Individuals who suffer from type 2 diabetes are usually characterized in part by down‐regulation of glucose transport genes such as glut4 and down‐regulation of mitochondrial lipid oxidizing genes such as carnitine palmitoyltransferase‐1 (Cpt‐1). Nuclear respiratory factor (NRF)‐1 is a mitochondrial transcriptional factor which is shown to be involved in glucose transport and is set as a potential therapeutic modality in the treatment and management of type 2 diabetes. In this study, we sought to access NRF‐1 and its target genes expression during exercise which is crucial in glucose transport and lipid oxidation.MethodFive to six weeks old male Wistar rats were exercised to identify the time point for an optimum increase in the levels of NRF‐1 and its target genes. Gastrocnemius muscles were harvested after 0, 2, 4, 6, 8, 10, 12, and 15 h post‐exercise and non‐exercise rats (control). Primers were used to amplify the region of following genes; Nrf‐1, glut 4, carnitine palmitoyl transferase (Cpt‐1 & Cpt‐2), peroxisome proliferator‐activated receptor gamma co‐activator 1 (Pgc‐1), mef2a, and acetyl‐CoA carboxylase‐1 (Acc‐1). Relative mRNA expression was normalized to the Actin reference gene.ResultsFrom the result of this study, cpt‐1, Nrf‐1, mef2a, glut4, cpt2, and Pgc‐1 showed 2.5, 8, 1.2, 4.1, 4.6, 3.5‐folds increases respectively after 8h post‐exercise compared with control whereas Acc‐1 showed a 3.1‐fold decrease in gene expression ratio after 6 h post‐exercise compared with control. Nrf‐1 binding to cpt‐1 and mef2a increased with 3 and 3.5‐folds respectively 6h post‐exercise compared with control.ConclusionConclusively, nrf‐1 was increased by exercise and also, it's binding to target genes which has huge implications in ameliorating type 2 diabetes and insulin resistance.

Enhancing lysosomal lipid metabolism prevents the loss of Kupffer cells in non-alcoholic steatohepatitis and attenuates liver pathology

Abstract During the development of non-alcoholic steatohepatitis (NASH), liver resident Kupffer cells (KCs) are progressively lost and replaced by monocyte-derived macrophages (MdMs). The impact of KC loss on NASH pathology is not currently known. Given the important role of KCs in maintaining tissue homeostasis and clearing blood-borne antigens, we hypothesized that KC depletion contributes to NASH pathogenesis. Thus, we aimed to elucidate the mechanism(s) of KC loss and to devise a strategy to enhance KC survival during NASH. We had previously shown that lipids can cause lysosomal cell death in macrophages. Using a mouse model of NASH, we discovered that KCs also develop phagolysosomal pathology. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and lipid metabolism that has been shown to rescue lysosomal dysfunction in other metabolic diseases. To test whether TFEB activation could protect against KC death in NASH, we generated a mouse model in which a KC-specific Cre induces expression of a TFEB overexpression construct (KCTFEB). Despite having similar body and liver weight as WT mice fed a NASH-inducing diet, KCTFEB mice had a striking preservation of KC number. Moreover, KCTFEB mice had reduced recruitment of pro-inflammatory MdMs and this was associated with lower liver triglyceride and injury. RNA sequencing of KCs from transgenic and WT mice revealed that TFEB induced the expression of several lysosomal and lipid metabolic genes. Together these findings provide important proof-of-concept evidence that KC loss contributes to disease pathology in NASH and suggest that targeting macrophage lysosomal/lipid metabolic function could be a useful strategy to enhance resident macrophage survival. Supported by grants from ADA-118IBS280, DDRCC-P30DK052574, NIH T32-AI007163, and NSF GRFP-DGE-1745038

Metabolic Reprogramming and Lipophagy Mediates Survival of Ascites Derived Metastatic Ovarian Cancer Cells.

Objective:The study was aimed at understanding the survival of metastatic ovarian cancer spheroids in the malignant ascites microenvironment. Methods:All the assays were performed using aseptically collected patient samples. The cells were characterized for the expression of ovarian and cancer stem cell markers using immunocytochemistry. The presence of lipid in the primary metastatic cancer spheroids were confirmed by neutral fat staining using Oil Red-O and transmission electron microscopy. The mRNA expression of autophagy and lipid metabolism genes was analyzed using RT-PCR. The lipid content was analyzed using lipidomics analysis. Etomoxir and chloroquine were used to study the effect of inhibition of autophagy in the metastatic cells. The data were analyzed using appropriate statistical tools and a p-value <0.05 was considered to be statistically significant.Results:Metastatic ovarian cancer spheroids exhibit cancer stem like properties and undergo a metabolic reprogramming when they disseminate from the primary tumor. We report here the accumulation of numerous cytoplasmic lipid droplets and lipophagic vesicles in the metastatic cells in contrast to their primary tumors. In addition we also report that these cells depend on lipophagy for the utilization of lipids rather than the conventional lipolytic pathway. The lipidomics analysis data reveals that the metastatic cells possess high levels of unsaturated fatty acids. We have also reported the occurrence of distinct accumulation of multiple nuclei in the patient derived metastatic cells. Inhibition of beta-oxidation and autophagic machinery using etomoxir and chloroquine resulted in cell death suggesting a potential mode to suppress metastatic cancer cells. Conclusion: Metabolic reprogramming is a characteristic feature of the metastatic ovarian cancer cells that are persisting in the malignant ascites. Targeting of the metastatic cells by gaining an insight into the various metabolic and molecular changes that occur in the metastatic niche provides a promising therapeutic approach in management of the disease.

Neuronal apoptosis drives remodeling states of microglia and shifts in survival pathway dependence.

Microglia serve critical remodeling roles that shape the developing nervous system, responding to the changing neural environment with phagocytosis or soluble factor secretion. Recent single-cell sequencing (scRNAseq) studies have revealed the context-dependent diversity in microglial properties and gene expression, but the cues promoting this diversity are not well defined. Here, we ask how interactions with apoptotic neurons shape microglial state, including lysosomal and lipid metabolism gene expression and dependence on Colony-stimulating factor 1 receptor (CSF1R) for survival. Using early postnatal mouse retina, a CNS region undergoing significant developmental remodeling, we performed scRNAseq on microglia from mice that are wild-type, lack neuronal apoptosis (Bax KO), or are treated with CSF1R inhibitor (PLX3397). We find that interactions with apoptotic neurons drive multiple microglial remodeling states, subsets of which are resistant to CSF1R inhibition. We find that TAM receptor Mer and complement receptor 3 are required for clearance of apoptotic neurons, but that Mer does not drive expression of remodeling genes. We show TAM receptor Axl is negligible for phagocytosis or remodeling gene expression but is consequential for microglial survival in the absence of CSF1R signaling. Thus, interactions with apoptotic neurons shift microglia toward distinct remodeling states and through Axl, alter microglial dependence on survival pathway, CSF1R.

Modulation Mechanism of Proanthocyanidins from Leaves of Bayberry (Myrica rubra Sieb. Et Zucc.) on Hyperlipemic Rats Induced by High-fat-diet

Aim: To investigate the lipid-lowering effect of proanthocyanidins from Bayberry leaf (BLP) in rat model of hyperlipidemia and to clarify the underlying molecular mechanism.&#x0D; Study Design: The study includes in-vitro and in-vivo experiments in rat model.&#x0D; Place and Duration of Study: College of Life Sciences, China Jiliang University, Zhejiang Province, China, between March 2021 to December 2021.&#x0D; Methodology: BLP were preliminarily characterized. The adsorption rate of BLP was determined based on in-vitro binding to bile acids. The effect of BLP on membrane transport of bile acids was examined through Caco-2 mono-layer in trans-well. The effect of BLP on serum enzyme activity and lipid metabolism genes expression were also investigated in a high-fat diet rat model.&#x0D; Results: Total poly-phenol and proanthocyanidins contents were 97.93% and 82.25% respectively, using gallic acid and Epigallocatechin-3-O-Gallate (EGCG) as equivalent. The total flavonoid content was 12.05% (quercetin as equivalent) and the average polymerization degree of BLP was determined as 4.51. And the in-vitro average binding rates of BLP to bile acids were all higher than 80%. Meanwhile, the membrane transport of bile acids in Caco-2 monolayer cells were significantly obstructed by BLP. Furthermore, the total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) concentrations in rat serum were markedly decreased after 28-day of BLP treatment. And the hepatic steatosis was significantly ameliorated in high-dose BLP treatment group compared with high fat group. High-dose administration of BLP significantly reduced the levels of 3-hydroxy-3-3methylglutary-CoA (HMG-CoA) reductase, while the levels of ATP binding cassette transporters (ABCG-5), liver X receptor-α (LXR-α) and cholesterol-7α-hydroxylase (CYP7A1) were significantly increased.&#x0D; Conclusion: BLP can mediate the serum lipid metabolism via preventing bile acids re-absorption, reducing oxidative stress and regulating the expression of lipid metabolism-related genes.

Epigallocatechin-3-gallate ameliorates hepatic damages by relieve FGF21 resistance and promotion of FGF21\u2013AMPK pathway in mice fed a high fat diet

BackgroundNon-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Epigallocatechin-3-gallate (EGCG) derived from extract of green tea and is well known for beneficial effects on anti-oxidative, anti-inflammatory, and anti-tumor activity. The present study aimed to implore its underlying mechanism for protective effect of NAFLD.MethodsMice were fed either high fat diet (HFD) or chow diet with or without EGCG treatment in HFD group, for up to 16 weeks. Histopathology, expression of lipid and glucose metabolism and lipogenesis-related gene expression were assessed. Primary mouse hepatocytes were treated with free fatty acids combined with different doses of EGCG for 48 h, expression of lipid and lipogenesis-related gene expression were assessed.ResultsThe results showed that EGCG attenuated HFD- and FFA-induced lipid accumulation in vivo and in vitro. EGCG can decrease the oxidative stress and promote Nrf2 level. Meanwhile EGCG alleviated FGF21 resistance and elevated FGFR/AMPK expression, which suggested an unrecognized mechanism of EGCG in ameliorating NAFLD.ConclusionsEGCG attenuated hepatocytes damage and dysfunction in NAFLD by alleviating FGF21 resistance and improve FGFR/AMPK pathway, mitigating oxidative stress. Our studies verified that EGCG may become a promising drug to treat or relieve NAFLD.

Membrane lipid metabolism influences chilling injury during cold storage of peach fruit

Peach fruit is prone to chilling injury (CI) during long-term low temperature (LT) storage, and develops protective mechanisms against LT stress. This study revealed that 4 °C storage induced the occurrence of CI in peach fruit by promoting the expression of membrane lipid metabolism genes and phosphatidic acid (PA) accumulation, and stimulated a protective mechanism for peach fruit against LT by increasing diacylglycerol (DAG), triacylglycerol (TAG) and several phosphatidylcholine (PC) components in the later storage stage. In contrast, 0 °C delayed the occurrence of CI in peach fruit by delaying the degradation of phospholipids, upregulation of fatty acid desaturase (FAD) and the process of fatty acid unsaturation, and maintaining higher levels of PC and PE. Results from this study provide new information on the mechanism of CI in peach fruit, and lay the foundation for the transcriptional regulation mechanism of CI and cold tolerance in peach fruit mediated by membrane lipid metabolism.

Cnot8 eliminates naïve regulation networks and is essential for naïve-to-formative pluripotency transition.

Mammalian early epiblasts at different phases are characterized by naïve, formative, and primed pluripotency states, involving extensive transcriptome changes. Here, we report that deadenylase Cnot8 of Ccr4-Not complex plays essential roles during the transition from naïve to formative state. Knock out (KO) Cnot8 resulted in early embryonic lethality in mice, but Cnot8 KO embryonic stem cells (ESCs) could be established. Compared with the cells differentiated from normal ESCs, Cnot8 KO cells highly expressed a great many genes during their differentiation into the formative state, including several hundred naïve-like genes enriched in lipid metabolic process and gene expression regulation that may form the naïve regulation networks. Knockdown expression of the selected genes of naïve regulation networks partially rescued the differentiation defects of Cnot8 KO ESCs. Cnot8 depletion led to the deadenylation defects of its targets, increasing their poly(A) tail lengths and half-life, eventually elevating their expression levels. We further found that Cnot8 was involved in the clearance of targets through its deadenylase activity and the binding of Ccr4-Not complex, as well as the interacting with Tob1 and Pabpc1. Our results suggest that Cnot8 eliminates naïve regulation networks through mRNA clearance, and is essential for naïve-to-formative pluripotency transition.

Identification of novel lipid biomarkers in xmrk- and Myc-induced models of hepatocellular carcinoma in zebrafish

BackgroundHepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by complex dysregulation of lipids. Increasing evidence suggests that particular lipid species are associated with HCC progression. Here, we aimed to identify lipid biomarkers of HCC associated with the induction of two oncogenes, xmrk, a zebrafish homolog of the human epidermal growth factor receptor (EGFR), and Myc, a regulator of EGFR expression during HCC.MethodsWe induced HCC in transgenic xmrk, Myc, and xmrk/Myc zebrafish models. Liver specimens were histologically analyzed to characterize the HCC stage, Oil-Red-O stained to detect lipids, and liquid chromatography/mass spectrometry analyzed to assign and quantify lipid species. Quantitative real-time polymerase chain reaction was used to measure lipid metabolic gene expression in liver samples. Lipid species data was analyzed using univariate and multivariate logistic modeling to correlate lipid class levels with HCC progression.ResultsWe found that induction of xmrk, Myc and xmrk/Myc caused different stages of HCC. Lipid deposition and class levels generally increased during tumor progression, but triglyceride levels decreased. Myc appears to control early HCC stage lipid species levels in double transgenics, whereas xmrk may take over this role in later stages. Lipid metabolic gene expression can be regulated by either xmrk, Myc, or both oncogenes. Our computational models showed that variations in total levels of several lipid classes are associated with HCC progression.ConclusionsThese data indicate that xmrk and Myc can temporally regulate lipid species that may serve as effective biomarkers of HCC progression.

Knockout of Stearoyl-CoA Desaturase 1 Decreased Milk Fat and Unsaturated Fatty Acid Contents of the Goat Model Generated by CRISPR/Cas9.

Goat milk contains a rich source of nutrients, especially unsaturated fatty acids. However, the regulatory mechanism of milk fat and fatty acid synthesis remains unclear. Stearoyl-CoA desaturase 1 (SCD1) is the key enzyme catalyzing monounsaturated fatty acid synthesis and is essential for milk lipid metabolism. To explore milk lipid synthesis mechanism in vivo, SCD1-knockout goats were generated through CRISPR/Cas9 technology for the first time. SCD1 deficiency did not influence goat growth or serum biochemistry. Plasma phosphatidylcholines increased by lipidomics after SCD1 knockout in goats. Whole-blood RNA-seq indicated alterations in biosynthesis of unsaturated fatty acid synthesis, cAMP, ATPase activity, and Wnt signaling pathways. In SCD1-knockout goats, milk fat percentage and unsaturated fatty acid levels were reduced but other milk components were unchanged. Milk lipidomics revealed decreased triacylglycerols and diacylglycerols levels, and the differential abundance of lipids were enriched in glycerolipid, glycerophospholipids, and thermogenesis metabolism pathways. In milk fat globules, the expression levels of genes related to fatty acid and TAG synthesis including SREBP1 were reduced. ATP content and AMPK activity were promoted, and p-p70S6K protein level was suppressed in SCD1-knockout goat mammary epithelial cells, suggesting that SCD1 affected milk lipid metabolism by influencing AMPK-mTORC1/p70S6K-SREBP1 pathway. The integrative analysis of gene expression levels and lipidomics of milk revealed a crucial role of SCD1 in glycerolipids and glycerophospholipids metabolism pathways. Our observations indicated that SCD1 regulated the synthesis of milk fat and unsaturated fatty acid in goat by affecting lipid metabolism gene expression and lipid metabolic pathways. These findings would be essential for improving goat milk nutritional value which is beneficial to human health.

Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes

Per- and polyfluoroalkyl substances (PFAS) are a class of environmental toxicants, and some, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have been associated with hepatic steatosis in rodents and monkeys. It was hypothesized that perfluorosulfonic acids (C4, 6, 8), perfluorocarboxylic acids (C4–14), perfluoro(2-methyl-3-oxahexanoic) acid (HFPO-DA), 1H, 1H, 2H, 2H-perfluorooctanesulfonic acid (6:2 FTS) along with 3 PFOS precursors could induce expression of lipid metabolism genes and lipid deposition in human hepatocytes. Five-donor pooled cryopreserved human hepatocytes were cultured and treated with 0.1% DMSO vehicle or various PFAS (0.25 to 25 μM) in media. After a 48-h treatment, mRNA transcripts related to lipid transport, metabolism, and synthesis were measured using a Quantigene Plex assay. After 72-h treatments, hepatocytes were stained with Nile Red dye to quantify intracellular lipids. Overall, PFAS were transcriptionally active at 25 μM. In this model, lipid accumulation was not observed with C8-C12 treatments. Shorter chain PFAS (C4-C5), 6:2 FTS, and PFOS precursor, metFOSA, induced significant liver lipid accumulation, and gene activation at lower concentrations than legacy PFAS. In summary short chain PFAS and other alternative PFAS were more potent gene inducers, and potential health effects of replacement PFAS should be critically evaluated in humans.

PM2.5 exposure during pregnancy is associated with altered placental expression of lipid metabolic genes in a US birth cohort

Inhalation of ambient PM2.5, shown to be able to cross the placenta, has been linked to adverse obstetric and postnatal metabolic health outcomes. The placenta regulates fetal growth and influences postnatal development via fetal programming. Placental gene expression may be influenced by intrauterine exposures to PM2.5. Herein, we explore whether maternal PM2.5 exposure during pregnancy alters placental gene expression related to lipid and glucose metabolism in a U.S. birth cohort, the Rhode Island Child Health Study (RICHS). Average PM2.5 exposure level was estimated linking residential addresses and satellite data across the three trimesters using spatio-temporal models. Based on Gene Ontology annotations, we curated a list of 657 lipid and glucose metabolism genes. We conducted a two-staged analysis by leveraging placental RNA-Seq data from 148 subjects to identify top dysregulated metabolic genes associated with PM2.5 (Phase I) and then validated the results in placental samples from 415 participants of the cohort using RT-qPCR (Phase II). Associations between PM2.5 and placental gene expression were explored using multivariable linear regression models in the overall population and in sex-stratified analyses. The average level of PM2.5 exposure across pregnancy was 8.0μg/m3, which is below the national standard of 12μg/m3. Phase I revealed that expression levels of 32 out of the curated list of 657 genes were significantly associated with PM2.5 exposure (FDR P<0.01), 28 genes showed differential expression modified by sex of the infant. Five of these genes (ABHD3, ATP11A, CLTCL1, ST6GALNAC4 and PSCA) were validated using RT-qPCR. Associations were stronger in placentas from male births compared to females, indicating a sex-dependent effect. These genes are involved in inflammation, lipid transport, cell-cell communication or cell invasion. Our results suggest that gestational PM2.5 exposure may alter placental metabolic function. However, whether it confers long-term programming effects postnatally, especially in a sex-specific matter, warrants further studies.

Tremella fuciformis Crude Polysaccharides Attenuates Steatosis and Suppresses Inflammation in Diet-Induced NAFLD Mice.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder characterized by an enhanced accumulation of lipids, which affects around 40% of the world’s population. The T. fuciformis fungus possesses immunomodulatory activity and other beneficial properties that may alleviate steatosis through a different mechanism. The present study was designed to evaluate the effect T. fuciformis crude polysaccharides (TFCP) on inflammatory and lipid metabolism gene expression, oxidative stress, and lipid profile. Mice were divided into groups receiving (a) a normal chow diet (NCD), (b) a methionine–choline-deficient (MCD) diet, and (c) a MCD diet with TFCP. Liver histopathology was performed, and the hepatic gene expression levels were estimated using qRT-PCR. The lipid profiles, ALT, AST, and efficient oxidative enzymes were analyzed using ELISA. The TFCP administration in the MCD-fed mice suppressed hepatic lipid accumulation, lipid metabolism-associated genes (HMGCR, FABP, SREBP, ACC, and FAS), and inflammation-associated genes (IL-1β, TLR4, TNF-α, and IL-6) whilst enhancing the expression of HNF4α genes. TFCP mitigated against oxidative stress and normalized healthy lipid profiles. These results highlighted that TFCP prevents NAFLD through the inhibition of oxidative stress and inflammation, suggesting TFCP would potentially be an effective therapeutic agent against NAFLD progression.

Comparing the effects of tumor necrosis factor alpha, lipopolysaccharide and palmitic acid on lipid metabolism and inflammation in murine 3T3-L1 adipocytes

AimsThis study aimed to develop a model of dysregulated lipid metabolism and inflammation by treating 3T3-L1 adipocytes with tumor necrosis factor alpha (TNFα), lipopolysaccharide (LPS), and palmitic acid (PA) individually or in combination to assess their effects and mechanism of action. Main methodsDifferentiated 3T3-L1 adipocytes were treated with TNFα (10 ng/mL), LPS (100 ng/mL), and PA (0.75 mM) individually or in combination for 24 h. Lipolysis, lipid content, inflammation, and the expression of lipid metabolism and inflammation genes were assessed by glycerol release quantification, Oil Red O staining, enzyme-linked immunosorbent assays, and quantitative reverse transcription-polymerase chain reaction, respectively. Key findingsExposure of 3T3-L1 adipocytes to TNFα stimulated lipolysis, reduced lipid accumulation, decreased adiponectin (ADIPOQ) secretion, and increased secretion of pro-inflammatory adipokines, monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β). These changes were accompanied by decreased expression of lipid metabolism genes, increased expression of pro-inflammatory genes (MCP-1 and IL-6), and decreased expression of the anti-inflammatory gene, ADIPOQ. Exposure to LPS and PA, alone or in combination did not affect these parameters, while co-treatment with TNFα, LPS, and PA enhanced lipolysis and decreased ADIPOQ secretion compared to TNFα treatment. SignificanceDysregulation of lipid metabolism and inflammation in 3T3-L1 adipocytes is attributed to TNFα rather than LPS and PA. We propose that exposing 3T3-L1 adipocytes to TNFα presents a suitable in vitro model of adipocyte dysfunction that closely resembles the complexity of obesity in vivo.

Different dietary combinations of high/low starch and fat with or without bile acid supplementation on growth, liver histopathology, gene expression and fatty acid composition of largemouth bass, Micropterus salmoides

High dietary levels of fat and/or starch can lower the growth and cause extensive liver inflammation that is linked to mortalities in largemouth bass, Micropterus salmoides. However, bile acids (BA) may mitigate these adverse effects. In a 2 × 2 × 2 factorial feeding trial, M. salmoides juveniles were fed different combinations of dietary high (HF), low fat (LF), high (HS) or low starch (LS) levels with or without BA supplementations at 1% for 8 weeks. A total of 8 isonitrogenous diets were formulated to include, HF/LS, HF/HS, LF/HS, LF/LS, HF/LS-BA, HF/HS-BA, LF/HS-BA and LF/LS-BA. Survival, growth performance, feeding efficiency, whole-body proximate composition, muscle/liver fatty acid composition, hepatic expression of growth regulator (GH/IGF1 axis), lipid metabolism (fatty acid synthase ‘FASN’ and cholesterol 7 alpha-hydroxylase ‘CYP7A1’) and antioxidant capacity (superoxide dismutase ‘SOD’) genes as well as liver histopathology were assessed. Results showed that among diets without BA, there was no significant effect on growth or feeding efficiency, but when BA was included this led to more variable effects including significantly higher weight gain in the LF/HS-BA group compared to all others fed BA. The HF, HS or their combination led to extensive hepatic inflammation, but BA appeared to partially mitigate this in the LF/HS group (i.e. LF/HS-BA). No abnormal liver histopathology was observed in the LF/LS and LF/LS-BA treatments. Muscle 22:6n-3 was significantly higher in the HF/LS and HF/HS-BA groups compared to those fed the HF/HS or LF/LS diets. Dietary fat had a significant effect on the moisture, crude lipid, and caloric content of M. salmoides. Hepatic expression of IGF-I and CYP7A1 were differentially modulated under different treatments. Overall, these results show that BA can alleviate some liver inflammation caused by high dietary starch; however the LF/LS diets led to a better balance between growth performance and liver health.

Exercise increases the expression of glucose transport and lipid metabolism genes at optimum level time point 6 h post-exercise in rat skeletal muscle

Exercise increases the expression of glucose transport and lipid metabolism genes at optimum level time point 6 h post-exercise in rat skeletal muscle

Evaluation of the Mechanism of Modified Lingguizhugan Decoction in the Treatment of Nonalcoholic Fatty Liver Disease.

Nonalcoholic steatohepatitis (NASH) may develop into cirrhosis and liver cancer, which imposes a great burden to individuals and society. Lingguizhugan decoction is a commonly used dampness dispelling medication in traditional Chinese medicine and is often used to treat those with phlegm and retained fluid from various causes and pathogeneses. The objective of this study was to explore the effect and mechanism of modified Lingguizhugan decoction (MLGZG) on lipid metabolism and the inflammatory response to identify a theoretical basis to promote its clinical application in NASH therapy. After treatment with MLGZG for 8 weeks, the weight of high-fat-diet (HFD)-fed NASH rats was significantly higher than that of rats in the normal group, and the weights in each dose group were significantly lower than those in the model group. The treatment groups (low, medium, and high doses) had different degrees of improvement in the changes in hepatocyte tissue structure, steatosis, and inflammatory infiltration. Compared with that in the normal group, the expression of TNF receptor-associated factor-3 (TRAF-3) and nuclear factor κB (NFκB) in the model group significantly increased to varying degrees. Compared with the NASH group, the treatment groups (low, middle, and high doses) showed modified lipid metabolism gene expression and decreased inflammatory factor expression levels. Modified Lingguizhugan decoction can improve the general condition of rats with nonalcoholic fatty liver disease by reducing the expression levels of TRAF3, NF-κB, the Toll-like receptor 4 (TLR-4) pathway, and related proteins, as well as the expression levels of lipid metabolism genes and cytokines.

Nostoc flagelliforme capsular polysaccharides from different culture conditions improve hyperlipidemia and regulate intestinal flora in C57BL/6J mice to varying degrees

Two capsular polysaccharides (WL-CPS-1 and GLU-CPS-1) purified from Nostoc flagelliforme under normal and mixotrophic culture conditions were used to investigate the hypolipidemic activity and effect on intestinal flora in C57BL/6J mice respectively. Their molecular weight and monosaccharide composition have been determined in previous studies. They both improved the lipid level by affecting the expression of lipid metabolism genes. They down-regulated the TNF-α and IL-1β levels in serum and up-regulated the activity of antioxidant enzymes in liver thus decreased the atherosclerosis index and MDA content. They up-regulated the short chain fatty acids (SCFAs) synthesis. They decreased the abundance of pathogenic bacteria and increased the abundance of probiotics positively correlated with SCFAs. Compared with WL-CPS-1, GLU-CPS-1 exhibited higher in vivo activity and enriched Odoribacter and Alloprevotella correlating with the gene expression of lipid metabolism, suggesting that the bioactivity of polysaccharides could be regulated by culture conditions. These findings contributed to application of N. flagelliforme polysaccharides with higher activity in hypolipidemia by adjusting culture conditions.

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p &lt; 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p &lt; 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.