Lipid Metabolism Research Articles

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report

BACKGROUND Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

Histology and transcriptomic analysis reveal effects of dietary fish oil and soybean oil on lipid absorption and immune inflammation in the foregut of adult female spotted scat (Scatophagus argus)

The foregut is the main site of lipid absorption in fish, but the effect of different lipid sources on the foregut lipid absorption and metabolism in adult female spotted scat is still unclear. In this experiment, adult female spotted scat (length = 19.48 ± 1.13cm, weight = 242.83 ± 50.90g) were fed two iso-nitrogenous (45% crude protein) and iso-lipidic (12.5% crude lipid) diets configured with either 8% fish oil (FO) or 8% soybean oil (SO) for 60 days. Histological observations, serum measurements and transcriptome sequencing were used to investigate the effects of the oil sources on the foregut. Histological observation showed that the foregut folds of the SO group were shorter and narrower than those of the FO group, and nuclear vacuolation and villous atrophy were observed in the intestinal cells of fish in the SO group, indicating an inflammatory reaction. Both serum triglyceride and total cholesterol levels were significantly higher in the FO group than in the SO group. Transcriptome analysis revealed 1355 differentially expressed genes between the FO and SO groups. Genes related to lipid metabolism (adipor2 and creb3l3) and cholesterol absorption and efflux (npc1l1 and sphk2) were up-regulated, whereas genes related to fatty acid synthesis and transport (fad1 and mfsd2ab) were down-regulated in the FO group. Circadian rhythm related genes ciart and nfil3, which are also involved in lipid metabolism, were up- and down-regulated, respectively in the FO group. The immune-related genes steap4, ddit4 and cldn6 which can inhibit inflammation, were up-regulated in the FO group, whereas pro-inflammation gene rnf225 was up-regulated in the SO group. In conclusion, compared with SO, FO may enhance the lipid absorption and reduce the inflammatory response in the foregut of the spotted scat. The results of this study provide a reference for the selection of dietary oil sources for adult female spotted scat.

Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species.

Asprosin (ASP) is a newly-identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP-deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP-deficiency significantly alleviated the high-fat diet-induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator-activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP-deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF-κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl-CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.

Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis.

The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans. This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS). We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and StarBase databases assisted in the construction of diagnostic molecule regulatory networks. The DrugBank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles. From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were down-regulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets.

Characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition in urological malignancies.

Being implicated during tumor migration, invasion, clonogenicity, and proliferation, the nicotinamide adenine dinucleotide (NAD)/-phosphate (NADP)-dependent dehydrogenase/reductase member 2 (DHRS2) has been considered to be induced upon inhibition of histone deacetylases (HDACi). In this study, we evaluated the current knowledge on the underlying mechanisms of the (epi)genetic regulation of DHRS2, as well as its function during tumor progression. DHRS2 expression was evaluated on mRNA- and protein-level upon treatment with HDACi by means of qRT-PCR and western blot analyses, respectively. Re-analysis of RNA-sequencing data gained insight into expression of specific DHRS2 isoforms, while re-analysis of ATAC-sequencing data shed light on the chromatin accessibility at the DHRS2 locus. Further examination of the energy and lipid metabolism of HDACi-treated urologic tumor cells was performed using liquid chromatography-mass spectrometry. Enhanced DHRS2 expression levels upon HDACi treatment were directly linked to an enhanced chromatin accessibility at the DHRS2 locus. Particularly the DHRS2 ENST00000250383.11 protein-coding isoform was increased upon HDACi treatment. Application of the HDACi quisinostat only mildly influenced the energy metabolism of urologic tumor cells, though, the analysis of the lipid metabolism showed diminished sphingosine levels, as well as decreased S1P levels. Also the ratios of S1P/sphingosine and S1P/ceramides were reduced in all four quisinostat-treated urologic tumor cells. With the emphasis on urologic malignancies (testicular germ cell tumors, urothelial, prostate, and renal cell carcinoma), this study concluded that elevated DHRS2 levels are indicative of a successful HDACi treatment and, thereby offering a novel putative predictive biomarker.

Licochalcone A alleviates ferroptosis in doxorubicin-induced cardiotoxicity via the PI3K/AKT/MDM2/p53 pathway.

Licochalcone A (Lico A), a flavonoid found in licorice, possesses multiple pharmacological activities in modulating oxidative stress, glycemia, inflammation, and lipid metabolism. This study aimed to explore the potential mechanism of Lico A in mitigating ferroptosis associated with doxorubicin-induced cardiotoxicity (DIC). Initially, network pharmacology analysis was applied to identify the active components present in licorice and their targeted genes associated with DIC. Subsequently, to assess the role of Lico A in a DIC mouse model, electrocardiograms, myocardial injury markers, and myocardial histopathological changes were measured. Additionally, cell viability, reactive oxygen species (ROS), ferrous iron, glutathione/glutathione disulfide (GSH/GSSG), and malondialdehyde (MDA) were measured in the cell model as hallmarks of ferroptosis. Finally, the PI3K/AKT/MDM2/p53 signaling pathway and ferroptosis-related proteins were measured in vitro and in vivo. Bioinformatics results revealed that 8 major compounds of licorice, including Lico A, primarily regulated targets such as p53 and the PI3K/AKT signaling pathways in DIC. In the mouse model of DIC, Lico A significantly ameliorated serum biomarkers, histopathology, and electrocardiogram abnormalities. Pretreatment with Lico A enhanced the viability of H9C2 cells treated with doxorubicin. Furthermore, Lico A administration resulted in decreased levels of ROS, ferrous iron, and MDA and increased levels of GSH/GSSG. At the protein level, Lico A increased the phosphorylation of PI3K/AKT/MDM2, reduced p53 accumulation, and induced the upregulation of SLC7A11 and GPX4 expression. However, selective inhibition of PI3K/AKT and plasmid-based overexpression of p53 significantly abolished the anti-ferroptosis functions of Lico A. In conclusion, Lico A attenuates DIC by suppressing p53-mediated ferroptosis through activating PI3K/AKT/MDM2 signaling.

In vitro toxicity of Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) on Human Renal and Hepatoma Cells

We evaluate the cytotoxicity, intracellular redox conditions, apoptosis, and methylation of DNMTs/TETs upon exposure to LiTFSI, a novel Per and Polyfluoroalkyl Substances (PFAS) commonly found in lithium-ion batteries, on human renal carcinoma cells (A498) and hepatoma cells (HepG2). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed both Perfluorooctane sulfonate (PFOS) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) had a dose-dependent effect on A498 and HepG2, with LiTFSI being less toxic. Intracellular redox conditions were assessed with a microplate reader and confocal, which showed a significant decrease in Reactive Oxygen Species (ROS) levels and an increase in Superoxide dismutase (SOD) content in both cells. Exposure to LiTFSI enhanced cell apoptosis, with HepG2 being more susceptible than A498. Quantitative analysis of mRNA expression levels of 19 genes associated with kidney injury, methylation, lipid metabolism and transportation was performed. LiTFSI exposure impacted kidney function by downregulating smooth muscle alpha-actin (Acta2) and upregulating transforming growth factor beta 1 (Tgfb1), B-cell lymphoma 2-like 1) Bcl2l1, hepatitis A virus cellular receptor 1 (Harvcr1), nuclear factor erythroid 2-like 2 (Nfe2l2), and hairy and enhancer of split 1 (Hes1) expression. LiTFSI exposure also affected the abundance of transcripts associated with DNA methylation by the expression of ten-eleven translocation (TET) and DNA methyltransferase (DNMT) genes. Furthermore, LiTFSI exposure induced an increase in lipid anabolism and alterations in lipid catabolism in HepG2. Our results provide new insight on the potential role of a new contaminant, LiTFSI in the regulation of oxidative stress, apoptosis and methylation in human renal carcinoma and hepatoma cells.

Nitric oxide alleviates programmed cell death induced by cadmium in Solanum lycopersicum seedlings through protein S-nitrosylation

Cadmium (Cd), as a non-essential and toxic heavy metal in plants, has deleterious effects on plant physiological and biochemical processes. Nitric oxide (NO) is one of the most important signaling molecules for plants to response diverse stresses. Here, we found that Cd-induced programmed cell death (PCD) was accompanied by NO bursts, which exacerbated cell death when NO was removed and vice versa. Proteomic analysis of S-nitrosylated proteins showed that the differential proteins in Cd-induced PCD and in NO-alleviated PCD mainly exist together in carbohydrate metabolism and amino acid metabolism, while some of the differential proteins exist alone in metabolism of cofactors and vitamins and lipid metabolism. Meanwhile, S-nitrosylation of proteins in porphyrin and chlorophyll metabolism and starch and sucrose metabolism could explain the leaf chlorosis induced by PCD. Moreover, protein transport protein SEC23, ubiquitinyl hydrolase 1 and pathogenesis-related protein 1 were identified to be S-nitrosylated in vivo, and their expressions were increased in Cd-induced PCD while decreased in NO treatment. Similar results were obtained in tomato seedlings with higher S-nitrosylation. Taken together, our results indicate that NO might be involved in the regulation of Cd-induced PCD through protein S-nitrosylation, especially proteins involved in PCD response.

Setd1A-mediated methylation of h3k4me3 inhibits ferroptosis in non-small cell lung cancer by regulating the WTAPP1/WTAP axis.

SETD1A is upregulated in non-small cell lung cancer (NSCLC) tissues. This study investigated the molecular mechanism of the SETD1A/WTAPP1/WTAP axis in NSCLC. Ferroptosis is a unique cell death mode driven by iron-reliant phospholipid peroxidation, which is regulated by multiple cellular metabolic pathways, including REDOX homeostasis, iron metabolism, mitochondrial activity and metabolism of amino acids, lipids and sugars. Thus, the levels of ferroptosis markers (MDA, SOD, GSH) were measured in vitro, and NSCLC cell behaviors were assessed. SETD1A-mediated H3K4me3 methylation was analyzed. SETD1A-exerted effects on ferroptosis and tumor growth in vivo were verified in nude mouse models. SETD1A was highly expressed in NSCLC cells. Silencing SETD1A suppressed NSCLC cell proliferation and migration, inhibited MDA, and enhanced GPX4, SOD, and GSH levels. SETD1A elevated WTAP expression through WTAPP1 upregulation by mediating H3K4me3 methylation in the WTAPP1 promoter region. WTAPP1 overexpression partly averted the promotional effect of silencing SETD1A on NSCLC cell ferroptosis. WTAP interference abrogated the inhibitory effects of WTAPP1 on NSCLC cell ferroptosis. Silencing SETD1A facilitated ferroptosis and accelerated tumor growth in nude mice through the WTAPP1/WTAP axis. SETD1A amplified WTAP expression through WTAPP1 upregulation by mediating H3K4me3 modification in the WTAPP1 promoter region, thus promoting NSCLC cell proliferation and migration and inhibiting ferroptosis.

Effects of dietary carbohydrate levels on growth performance, feed utilization, liver histology and intestinal microflora of juvenile tiger puffer, Takifugu rubripes

An 8-week feeding trial was conducted to investigate the effects of dietary carbohydrate levels on growth performance, body composition, and plasma biochemical parameters, liver and gut histology, and intestinal microbiota of Takifugu rubripes. Five isonitrogenous and isolipidic experimental diets were formulated with graded levels of cassava starch: 0% (C0), 8% (C8), 16% (C16), 24% (C24), and 32% (C32). The results showed that weight gain rate, specific growth rate (SGR) and protein efficiency ratio significantly increased in C16 and C24 groups (P < 0.05), while the feed conversion ratio expressed an opposite trend. Feeding rate is decreased with the increasing of carbohydrate levels (P < 0.05). Liver lipid content was dramatically increased in C24 treatment (P < 0.05). The intestinal amylase activity and muscle glycogen content were higher than other groups (P < 0.05). Plasma glucose levels were increased in C24 and C32 groups (P < 0.05). In addition, the abundance of intestinal potentially pathogenic bacteria (Staphylococcus) decreased, and the intestinal probiotics (Lactobacillus) increased with the increasing of dietary carbohydrate level (P < 0.05). The intestinal bacteria, indicated by Sobs, Chao and Shannon indexes, were more diverse with the increasing of the carbohydrate level (P < 0.05), meanwhile the abundance of transport and metabolism of carbohydrate, lipid and amino acid were enhanced with the increasing of carbohydrate levels (P < 0.05). In conclusion, appropriate supplementation of carbohydrate in diet promoted growth performance and feed utilization of juvenile Takifugu rubripes, and increased the liver lipid and muscle glycogen content, as well as intestinal microbial diversity. Based on the quadratic regression between SGR and carbohydrate levels, the optimal dietary carbohydrate level of juvenile Takifugu rubripes is 21.6%.

Integrated multiple-omics reveals the regulatory mechanism underlying the effects of homologous Bacillus tequilensis (GCB-3) on growth performance of grass carp (Ctenopharyngodon idellus)

The purpose of this study was to investigate the regulatory mechanism of Bacillus tequilensis (GCB-3) in improving the growth performance of grass carp by microbiome and targeted metabolomics analysis. Fish were fed with different amounts of GCB-3 including B0 (0 CFU/g), B6 (1×106 CFU/g), B7 (1×107 CFU/g), B8 (1×108 CFU/g), and B9 (1×109 CFU/g) for 8 weeks. The results indicate that with the increase of dietary GCB-3 concentration, grass carp showed a significant linear trend in growth performance, and appetite factors showed a significant linear and quadratic trend, the growth performance and appetite-promoting factors in the B8 group reach their maximum value in the B8 group. Microbiome analysis found that Proteobacteria and Actinobacteria were the most abundant phylum in the gut microbiota of grass carp. The functional potential predicted that GCB-3 affected the synthesis and degradation of carbohydrates, amino acids, fatty acids and lipids. It found that GCB-3 also affected the tricarboxylic acid (TCA) cycle VII (acetate-producers) pathway. The results of targeted metabolomics showed a significant linear and quadratic increase in intestinal acetate with GCB-3 concentration and a maximum in the B8 group. The results of the correlation analysis showed a significant positive correlation between Actinobacteria abundance and acetic acid content, and also between TCA cycle VII (acetate-producers) pathway abundance and Actinobacteria abundance and acetic acid content. In B8 group, grass carp showed a faster regulation speed of blood glucose levels after glucose injection, and the GLP-1 content remained stable. The activities of glycolytic enzymes, lipolytic enzymes, protein metabolism enzymes, and their related mRNA expression levels in grass carp showed a linear or quadratic increasing trend. However, the expression levels of gluconeogenic enzymes and fatty acid synthesis enzyme related mRNA showed an opposite trend. In summary, the addition of 1×108 CFU/g GCB-3 in grass carp feed can improve the abundance of dominant bacterial phyla in the intestine, especially Actinobacteria, increase the concentration of intestinal acetate, provide substrate for the TCA cycle VII (acetate-producers) pathway, thereby regulating the nutrient metabolism of grass carp and ultimately promoting growth.

Ginseng polysaccharide components attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

Insights into the antibacterial effectiveness of linalool against Shigella flexneri on pork surface: Changes in bacterial growth and pork quality

Shigella flexneri has the ability to contaminate pork and cause foodborne diseases. This study aimed to examine the effectiveness of linalool (a natural preservative) against S. flexneri and explore its potential application in contaminated pork. The results showed that linalool was capable of damaging the cell membrane and binding to the DNA of S. flexneri, and inhibiting biofilm formation and disrupting mature biofilms. The antibacterial effectiveness of linalool on the surface of pork was further demonstrated by analyzing the physicochemical properties of the pork (i.e., weight loss rate, pH value, color index, and TVB-N value) and its protein profiles. Linalool did not completely kill S. flexneri in pork at minimum bactericidal concentration (MBC) concentration and its antibacterial effect of linalool was stronger during the initial stage of storage. During storage, linalool influenced the abundance of specific proteins in the pork, particularly those involved in pathways related to fat metabolism. These findings offer novel insights into the antibacterial efficacy of linalool and its underlying mechanism in pork.

Whole transcriptome sequencing reveals the activity of the PLA2 family members in Androctonus crassicauda (Scorpionida: Buthidae) venom gland.

Phospholipase A2 is the most abundant venom gland enzyme, whose activity leads to the activation of the inflammatory response by accumulating lipid mediators. This study aimed to identify, classify, and investigate the properties of venom PLA2 isoforms. Then, the present findings were confirmed by chemically measuring the activity of PLA2. The sequences representing PLA2 annotation were extracted from the Androctonus crassicauda transcriptome dataset using BLAS searches against the local PLA2 database. We found several cDNA sequences of PLA2 classified and named by conducting multiple searches as platelet-activating factor acetylhydrolases, calcium-dependent PLA2s, calcium-independent PLA2s, and secreted PLA2s. The largest and smallest isoforms of these proteins range between approximately 70.34 kDa (iPLA2) and 17.75 kDa (cPLA2). Among sPLA2 isoforms, sPLA2GXIIA and sPLA2G3 with ORF encoding 169 and 299 amino acids are the smallest and largest secreted PLA2, respectively. These results collectively suggested that A. crassicauda venom has PLA2 activity, and the members of this protein family may have important biological roles in lipid metabolism. This study also revealed the interaction between members of PLA2s in the PPI network. The results of this study would greatly help with the classification, evolutionary relationships, and interactions between PLA2 family proteins in the gene network.

Thyroid function changes during growth hormone therapy in pediatric patients: a controlled study and review of recent data

Introduction: Growth hormone therapy is a cornerstone treatment for children with GHD and ISS. Its impact on the hypothalamic-pituitary-thyroid axis, however, has been a subject of ongoing research. This review compiles findings from several studies spanning three decades and contrasts them with recent data to enhance our understanding of thyroid function dynamics during GH therapy. Review of Literature: Early Observations (1992-2005) Pirazzoli et al. (1992) and Tang et al. (1997) were among the first to document changes in thyroid function due to GH therapy, noting enhanced peripheral conversion of T4 to T3 and a prevalence of subclinical hypothyroidism. Wyatt et al. (1998) reported significant decreases in T4 and increases in T3, indicating a notable shift in thyroid hormone levels early in GH therapy. Mid-Term Studies (2005-2015) Seminara et al. (2005) and Kalina-Faska et al. (2004) reported changes in thyroid function, particularly a decrease in T4 levels and a transient increase in fT3 during the early stages of GH therapy. · Recent Developments (2016-Present) Wang Ying and Liang Furong (2016) emphasized the need for vigilant monitoring of thyroid hormone levels, aligning with Zheng et al. (2014) who noted improvements in lipid metabolism without significant thyroid function impacts. Glynn et al. (2017, 2018) and Kucharska et al. (2021) focused on the complexities of the biological effects of GH-induced changes in thyroid hormones. Comparison with our Data Our recent study reveals subtle changes in thyroid function in GH-treated children with GHD and ISS. We observed a slight decrease in mean FT4 and an increase in mean TSH in the GH treatment group, stable TSH and decreased FT4 in the ISS treatment group, and significant decreases in both FT4 and TSH in the no-treatment group. These findings corroborate the trend seen in earlier studies, highlighting the multifaceted nature of thyroid function changes during GH therapy. Conclusions: The review underscores that GH therapy can significantly influence thyroid function, necessitating regular monitoring of thyroid hormone levels. The variation in thyroid responses suggests a complex interaction between GH therapy and the hypothalamic-pituitary-thyroid axis, which may be influenced by factors like age, severity of GHD, and duration of GH treatment.

Comprehensive analysis of changes in expression of lncRNA, microRNA and mRNA in liver tissues of chickens with high or low abdominal fat deposition.

1. The liver of chickens is a dominant lipid biosynthetic tissue and plays a vital role in fat deposition, particularly in the abdomen. To determine the molecular mechanisms involved in its lipid metabolism, the livers of chickens with high (H) or low (L) abdominal fat content were sampled and sequencing on long non-coding RNA (lncRNA), messenger RNA (mRNA) and small RNA (microRNA) was performed.2. In total, 351 expressed protein-coding genes for long non-coding RNA (DEL; 201 upregulated and 150 downregulated), 400 differentially expressed genes (DEG; 223 upregulated and 177 downregulated) and 10 differentially expressed miRNA (DEM; four upregulated and six downregulated) were identified between the two groups. Multiple potential signalling pathways related to lipogenesis and lipid metabolism were identified via pathway enrichment analysis. In addition, 173 lncRNA - miRNA - mRNA interaction regulatory networks were identified, including 30 lncRNA, 27 mRNA and seven miRNA.3. These networks may help regulate lipid metabolism and fat deposition. Five promising candidate genes and two lncRNA may play important roles in the regulation of adipogenesis and lipid metabolism in chickens.

Elucidating the Role of Lipid-Metabolism-Related Signal Transduction and Inhibitors in Skin Cancer

Lipids, as multifunctional molecules, play a crucial role in a variety of cellular processes. These include regulating membrane glycoprotein functions, controlling membrane trafficking, influencing apoptotic pathways, and affecting drug transport. In addition, lipid metabolites can alter the surrounding microenvironment in ways that might encourage tumor progression. The reprogramming of lipid metabolism is pivotal in promoting tumorigenesis and cancer progression, with tumors often displaying significant changes in lipid profiles. This review concentrates on the essential factors that drive lipid metabolic reprogramming, which contributes to the advancement and drug resistance in melanoma. Moreover, we discuss recent advances and current therapeutic strategies that employ small-molecule inhibitors to target lipid metabolism in skin cancers, particularly those associated with inflammation and melanoma.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2=0.319, P=0.037, and BMD was also positively correlated with pectoral muscle density, R2=0.329, P=0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Pinctada martensii Hydrolysate Modulates the Brain Neuropeptidome and Proteome in Diabetic (db/db) Mice via the Gut–Brain Axis

Pinctada martensii hydrolysate (PMH) has been proved to have the effect of ameliorating disorders of glucose and lipid metabolism in db/db mice, but the mechanism of its hyperglycemia effect is still unclear. Bacterial communities in fecal samples from a normal control group, a diabetic control group, and a PMH-treated diabetes mellitus type 2 (T2DM) group were analyzed by 16S gene sequencing. Nano LC-MS/MS was used to analyze mice neuropeptides and proteomes. The 16S rDNA sequencing results showed that PMH modulated the structure and composition of the gut microbiota and improved the structure and composition of Firmicutes and Bacteroidetes at the phylum level and Desulfovibrionaceae and Erysipelatoclostridiaceae at the family level. Furthermore, the expressions of functional proteins of the central nervous system, immune response-related protein, and proteins related to fatty acid oxidation in the brain disrupted by an abnormal diet were recovered by PMH. PMH regulates the brain neuropeptidome and proteome and further regulates blood glucose in diabetic mice through the gut–brain axis. PMH may be used as a prebiotic agent to attenuate T2DM, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

Loss of Bcl-3 regulates macrophage polarization by promoting macrophage glycolysis.

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.