Lipid Metabolism Research Articles

Bach2 repression of CD36 regulates lipid-metabolism-linked effector functions in follicular B cells

The transcription repressor Bach2 plays a crucial role in shaping humoral immunity, but its cell-autonomous function remains elusive. Here, we reveal the mechanism by which Bach2 regulates effector cell maturation in peripheral B cells. In response to Toll-like receptor (TLR) agonists, Bach2 deficiency promotes the differentiation of follicular, but not marginal zone, B cells into effector cells, producing interleukin (IL)-6 and antibodies. This phenomenon is associated with changes in lipid metabolism, such as increases in CD36 expression, lipid influx, and fatty acid oxidation. Consistent with this, Bach2-deficient B cells exhibit elevated levels of mitochondrial oxidative stress, lipid peroxidation, and p38 activation. Mechanistically, Bach2 acts as a repressor of Cd36, and inhibition of CD36 or fatty acid oxidation reduces the differentiation of naive B cells into IL-6- and antibody-secreting cells. These results indicate Bach2 as a key metabolic checkpoint regulator crucial for maintaining a functionally quiescent state of follicular B cells.

Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.

Polypeptides from Sea Cucumber Acaudina molpadioides Ameliorate Glucolipid Metabolism Disorder and Reverse Gut Microbiota Dysbiosis in Type 2 Diabetic Rats

ABSTRACT The therapeutic effects of polypeptides isolated from sea cucumber Acaudina molpadioides (AP) on the intestinal flora and glycolipid metabolic disturbance in high-fat diet/STZ-induced T2DM rats were investigated. The results showed that AP intervention notably ameliorated blood glucose, lipid levels, and pancreas injuries in T2DM rats. The diversity of intestinal microbial communities in T2DM rats was also enhanced by AP. Moreover, microbially derived short-chain fatty acids concentrations markedly improved in the feces of diabetic rats after AP treatment. These results suggest that AP played a protective role in T2DM rats by regulating glucose, lipid metabolism, and altering intestinal microbial.

Association analyses of nutritional markers with Parkinson’s disease and Alzheimer’s disease

IntroductionParkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. MethodsA total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P < 0.0045 after bonferroni correction. ResultsMultifactor risk analysis showed that ApoB, LDL, and TC reduce PD risk, while HCY increase PD risk. ApoA1 and HCY are protective and risk factors for AD, respectively. ConclusionThe cross-sectional study demonstrates that HCY and lipid metabolism markers are associated with PD and AD risks. Our findings support the involvement of one-carbon metabolism and lipid metabolism disturbance in PD and AD.

Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of gall bladder.

Carcinoma of gall bladder (CAGB) has poor prognosis. Molecular analysis of bile could classify indicators of CAGB. Bile samples (n=87; training cohort) were screened for proteomics and metabolomics signatures of cancer detection. In bile, CAGB showed distinct proteomic (217up-, 258 downregulated) and metabolomic phenotype (111 up-, 505 downregulated, p<0.05, FC>1.5, FDR<0.01) linked to significantly increased inflammation (coagulation, arachidonic acid, bile acid) and alternate energy pathways (pentose-phosphate pathway, amino-acid, lipid metabolism) and decreased glycolysis, cholesterol metabolism, PPAR, RAS and RAP1 signaling, oxidative phosphorylation, and others compared to GS or HC (p<0.05). Bile proteins/metabolites signatures showed significant correlation (r2>0.5, p<0.05) with clinical parameters. Metabolite/protein signature-based probability of detection for CAGB (cancer) was >90% (p<0.05) with AUC>0.94. Validation of top four metabolites: Toluene, 5,6-DHET, Creatine, and Phenylacetaldehyde in separate cohorts (n=80; bile [T1] and paired plasma [T2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. Tissue validation showed bile 5,6 DHET positively correlated with tissue PCNA (proliferation), and Caspase-3 linked to cancer development (r2>0.5, p<0.05). In conclusion, the bile molecular landscape provides critical molecular understanding and outlines metabolomic indicator panels for early CAGB detection.

Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy

BackgroundThe cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson’s disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis.MethodsTo this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc.ResultsOral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling.ConclusionOur study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.

A Comprehensive Review on the Anti-Obesity Potential of Limonia acidissima L., and its Bioactive Compounds: Mechanisms and Applications in Weight Management

Introduction: Obesity is a global health challenge associated with numerous metabolic disorders, including diabetes and cardiovascular disease. With growing interest in natural remedies for weight management, Limonia acidissima L., has garnered attention due to its rich bioactive composition. Objectives: This systematic review evaluates the anti-obesity potential of Limonia acidissima L., and its key bioactive compounds, including fibres, phytosterols, saponins, polyphenols, flavonoids, and ascorbic acid. Methods: A comprehensive search of databases such as PubMed, Scopus, and Google Scholar was conducted, focusing on studies published between 2000 and 2023 that investigated the metabolic effects of these compounds on lipid and carbohydrate metabolism, fat absorption, and glucose regulation. Results: The results demonstrated that Limonia acidissima L., significantly reduced body weight and fat mass, improved lipid profiles, and enhanced insulin sensitivity in both animal and human studies.Phytosterols and saponins played key roles in modulating lipid metabolism, while fibres and polyphenols were found to regulate carbohydrate metabolism and improve glycemic control. Additionally, the synergistic effects of multiple bioactive compounds amplified their collective anti-obesity potential, with few reported adverse effects, suggesting a favourable safety profile. The discussion highlights the multifaceted mechanisms through which Limonia acidissima L., combats obesity, emphasizing its ability to target multiple metabolic pathways simultaneously.While the findings are promising, the need for further large-scale clinical trials to validate these effects in diverse populations is underscored. Conclusions: In conclusion, Limonia acidissima L., emerges as a potent natural remedy for obesity management, with strong potential for inclusion in weight loss supplements and functional foods.Its bioactive compounds offer a comprehensive and safe approach to addressing the global obesity epidemic, although further research is needed to establish its long-term efficacy and optimal use.

ARMC5 selectively degrades SCAP-free SREBF1 and is essential for fatty acid desaturation in adipocytes

SREBF1 plays the central role in lipid metabolism. It has been known that full-length SREBF1 that did not associate with SCAP (SCAP-free SREBF1) is actively degraded, but its molecular mechanism and its biological meaning remain unclear. ARMC5-CUL3 complex was recently identified as E3 ubiquitin ligase of full-length SREBF. Although ARMC5 was involved in SREBF pathway in adrenocortical cells, the role of ARMC5 in adipocytes has not been investigated. In this study, adipocyte-specific Armc5 knockout mice were generated. In the white adipose tissue (WAT) of these mice, all the stearoyl-CoA desaturase (Scd) were drastically downregulated. Consistently, unsaturated fatty acids were decreased and saturated fatty acids were increased. The protein amount of full-length SREBF1 were increased, but ATAC-Seq peaks at the SREBF1-binding sites were markedly diminished around the Scd1 locus in the WAT of Armc5 knockout mice. Armc5-deficient 3T3-L1 adipocytes also exhibited downregulation of Scd. Mechanistically, disruption of Armc5 restored decreased full-length SREBF1 in CHO cells deficient for Scap. Overexpression of Scap inhibited ARMC5-mediated degradation of full-length SREBF1, and overexpression of Armc5 increased nuclear SREBF1/full-length SREBF1 ratio and SREBF1 transcriptional activity in the presence of exogenous SCAP. These results demonstrated that ARMC5 selectively removes SCAP-free SREBF1 and stimulates SCAP-mediated SREBF1 processing, hence is essential for fatty acid desaturation in vivo.

The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium

Age-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype. Chronic CSE altered the metabolic profile in both LR and HR iPSC-RPE and caused a dose-dependent reduction in mitochondrial function despite an increase in mitochondrial content. Notably, cells with the HR CFH SNP showed a greater reduction in maximal respiration and ATP production. Significant genotype-dependent changes in the proteome were observed for HR RPE at baseline (cytoskeleton, MAPK signaling) and after CSE exposure, where a less robust upregulation of the antioxidants and significant downregulation in proteins involved in nucleic acid metabolism and membrane trafficking were noted compared to LR cells. In LR cells, uniquely upregulated proteins were involved in lipid metabolism and chemical detoxification. These genotype-dependent differences at baseline and in response to chronic CSE exposure suggest a broader role for CFH in modulating the response to oxidative stress in RPE and provides insight into the interaction between environmental and genetic factors in AMD pathogenesis.

The Combined Inhibition of SREBP and mTORC1 Signaling Synergistically Inhibits B-Cell Lymphoma.

The sterol regulatory element-binding protein (SREBP) pathway is essential for maintaining sterol homeostasis during B cell activation and germinal center B cell proliferation. However, its potential as a therapeutic target to treat B-cell lymphoma remains unclear. We examined SREBP protein expression in human B-cell lymphoma samples using immunohistochemistry. Additionally, we conducted invitro studies using SREBP signaling inhibitors in combination with rapamycin to assess their effects on cell proliferation and lipid metabolism in B-cell lymphoma cells. Our analysis revealed high levels of SREBP2 protein expression in human B-cell lymphoma samples. Inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) with Fatostatin or Simvastatin effectively suppressed B-cell lymphoma cell proliferation. However, B-cell lymphoma cells responded to statin treatment by activating the mTORC1-pS6 pathway, suggesting a compensatory mechanism to overcome statin-induced cell cycle arrest. Combining low-dose statin treatment with the mTOR inhibitor rapamycin produced a synergistic effect, significantly inhibiting B-cell lymphoma proliferation, cell cycle progression, and lipid raft formation. These results highlight the potential of a combined therapeutic approach targeting both SREBP and mTORC1 as a novel strategy for treating B-cell lymphoma.

The Impact of Various Types of Exercise on Lipid Metabolism in Patients with Type 2 Diabetes and Concurrent Overweight/Obesity: A Narrative Review

The Impact of Various Types of Exercise on Lipid Metabolism in Patients with Type 2 Diabetes and Concurrent Overweight/Obesity: A Narrative Review

Pharmacophore-guided in-silico discovery of SIRT1 inhibitors for targeted cancer therapy

Epigenetic modifier, Sirtuin (SIRTs) is a family of seven isoforms (SIRT1-7) and nicotinamide adenine dinucleotide (NAD+) dependent class III histone deacetylase (HDACs) protein. SIRT1 in association with the p53 protein can regulate crucial cell processes such as glucose metabolism, lipid metabolism, mitochondrial biogenesis, DNA repair, oxidative stress, apoptosis, and inflammation through the process of deacetylation. When SIRT1 deacetylates p53, it loses its tumor suppression property. To promote apoptosis and decrease cell proliferation by inhibiting SIRT1 protein and ultimately raising the acetylation of p53 to regain its tumor suppressor function. Though we have many SIRT1 protein inhibitors, they exhibited off-target effects and inefficiency at the clinical trial stage. This study has been executed to identify more potentially effective and reliable SIRT1 inhibitors that can perform better than the existing options. To do so, pharmacophore-based screening of compound libraries followed by virtual screening, pharmacokinetic, drug-likeness, and toxicity studies were conducted which gave 42 compounds to evaluate further. Subsequently, exhaustive molecular docking and molecular dynamics simulation predicted four potential hits to inhibit the SIRT1 protein better than the reference compound. Further studies such as principal components analysis, free energy landscape, and estimation of binding free energy were done which concluded Hit4 (PubChem ID: 55753455) to be a novel and potent SIRT1 small molecule inhibitor among the others. The total binding free energy for Hit4 was found to be -44.68kcal/mol much better than the reference complex i.e., -29.38kcal/mol.

Heightened TPD52 linked to metabolic dysfunction and associated abnormalities in zebrafish

The tumor protein D52 (TPD52) gene encodes a proto-oncogene protein associated with various medical conditions, including breast and prostate cancers. It plays a role in multiple biological pathways such as cell growth, differentiation, and apoptosis. The function of TPD52 in lipid droplet biosynthesis has been investigated in vitro. However, its precise role in lipid metabolism in animal models is not fully understood. To investigate the functions of TPD52 in vivo, we performed a conditional TPD52 protein expression analysis using a Tet-off transgenic system to establish conditionally expressed Tpd52 transgenic zebrafish. The effect of Tpd52 on lipogenesis was assessed using various methods, including whole-mount Oil Red O staining, histological examination, and measurement of inflammatory markers and potential targets using real-time quantitative polymerase chain reaction and immunoblotting in Tpd52 fish. Zebrafish with increased Tpd52 levels exhibited notable weight gain and the enlargement of fat deposits, which were mainly attributed to an increase in the volume of adipocytes. Moreover, Tpd52 overexpression was correlated with the triggering of the adipocyte differentiation signaling pathway. During adipocytic differentiation in response to nutrient status, our observations revealed adipogenesis, nonalcoholic fatty liver disease, and metabolic cardiomyopathy (MCM) in Tpd52 transgenic zebrafish. To gain a deeper understanding of the contribution of these proteins to the regulation of cellular growth, we investigated the expression of their corresponding genes and proteins in zebrafish. In the present study, the activated protein kinase pathway was identified as the primary target of TPD52. Adult Tpd52 zebrafish showed increased lipid accumulation, resulting in the development of visceral obesity, nonalcoholic fatty liver disease, and MCM. These findings strongly suggest that TPD52 actively contributes to adipose tissue expansion and its subsequent effects. This investigation provides compelling evidence that Tpd52 facilitates adipocyte development and related metabolic comorbidities in zebrafish.

Evaluating the therapeutic effect of different forms of silymarin on liver status and expression of some genes involved in fat metabolism, antioxidants and anti-inflammatory in older laying hens.

Silymarin, the predominant compound of milk thistle, is an extract took out from milk thistle (Silybum marianum) seeds, containing a mixture of flavonolignans with strong antioxidant capability. The experiment was conducted using 70 Lohmann LSL-Lite hens at 80 weeks of age with 7 treatments each with 10 replicates. Treatments included: (1) control diet without silymarin, (2) daily intake of 100mg silymarin powder/kg body weight (BW) (PSM100), (3) daily intake of 200mg silymarin powder/kg BW (PSM200), (4) daily intake of 100mg nano-silymarin/kg BW (NSM100), (5) daily intake of 200mg nano-silymarin/kg BW (NSM200), (6) daily intake of 100mg lecithinized silymarin/kg BW (LSM100) and (7) daily intake of 200mg lecithinized silymarin/kg BW (LSM200). The birds were housed individually, and diets were fed for 12 weeks. Scanning electron microscopy showed that NSM was produced with the average particle size of 20.30nm. Silymarin treatment improved serum antioxidant enzyme activity. All groups receiving silymarin showed a decrease in liver malondialdehyde content, expression of fatty acid synthase, tumour necrosis factor alpha, interleukin 6 (IL-6) genes in the liver, and hepatic steatosis than the control, except those fed the PSM100 diet. There were decreases in liver dry matter and fat contents, non-alcoholic fatty liver disease and hepatocyte ballooning, and an increase in glutathione peroxidase gene expression and a decrease in iNOS gene expression in birds fed the NSM100, NSM200, LSM100 and LSM200 diets compared to the control group. Moreover, all groups receiving silymarin showed a significant decrease in liver weight compare to the control group. Overall, the effects of silymarin when converted to NSM or LSM and offered at the level of 200mg/kg BW were more pronounced on the hepatic variables and may be useful in the prevention of the liver disease in older laying hens.

Fresh insights into the light‐induced pineal gland circadian rhythm transmission mechanism derived from mRNA and miRNA profiling

AbstractThe circadian clock significantly impacts animal health and productivity, with light playing a crucial role in regulating circadian rhythms. However, the mechanisms behind light‐induced circadian transmission remain unclear, particularly in light‐sensitive avian species. The pineal gland is a key component acting as the photosensitive master oscillator in the avian clock system. Using transcriptome sequencing and small RNA sequencing technologies, we identified circadian genes and miRNAs in the chick pineal gland under light–dark and sudden constant‐light conditions. We observed rhythmic oscillations in up to 1299 genes during the light–dark cycle, with 400 genes maintaining rhythms under constant light. Our findings highlight the light‐sensitive temporal organization in birds as the phase distribution of circadian genes in the pineal gland correlates with light exposure changes. A novel regulatory mechanism involving light, cyclic adenosine monophosphate, cyclic guanosine monophosphate, light‐sensitive miRNAs, such as gga‐miR‐34b‐5p, and light‐sensitive circadian genes, such as CRY2, was discovered to participate in the light input system of the chick pineal clock, through which light regulates the oscillators and outputs of the circadian clock system. Additionally, transcriptomic analysis, liquid chromatography–mass spectrometry, and Oil Red O staining revealed cyclic changes in lipid synthesis and metabolism throughout the circadian day, which may be a key mechanism through which the circadian clock influences pineal physiology. Our results enhance the understanding of light‐induced circadian transmission mechanisms and identify potential targets for optimizing the circadian clock through light.

MiRNA novel-216 regulated fatty acid composition and progesterone synthesis in goat granulosa cells by targeting TPD52

Granulosa cells in the ovaries of livestock are crucial for secreting steroid hormones that regulate follicular development, with lipid synthesis and metabolism playing key roles in this process. The molecular mechanisms behind steroid hormone secretion regulated by fatty acid metabolism in goat granulosa cells have been unclear. Our previous transcriptome analysis of Yunshang black goat ovaries revealed that miR-novel-216, which had lower expression in high-fertility goats, might regulate granulosa cell function. We further investigated the role of miR-novel-216 by isolating and culturing goat granulosa cells in vitro, and found that it inhibits cell proliferation, lipid accumulation, and progesterone synthesis in goat granulosa cells. The qTar and miRanda analyses predicted TPD52 as a target of miR-novel-216, confirmed by dual luciferase and transfection assays. Previous studies have shown that progesterone synthesis in granulosa cells is closely related to free fatty acid composition. We investigated the effect of in vitro construction of TPD52 overexpression and interference plasmids on the free fatty acid content of goat granulosa cells using mass spectrometry sequencing. The results showed that overexpression of TPD52 in goat granulosa cells significantly increased free fatty acid content and promoted granulosa cell proliferation, lipid accumulation, and progesterone synthesis, whereas the opposite was true for inhibition of TPD52. It was shown that miR-novel-216 affects granulosa cell proliferation and free fatty acid levels by regulating the expression of TPD52, which increases reproductive hormone secretion and promotes polytocous trait in goats. This provides a foundation for developing breeding strategies to improve goat fertility.

Diosgenin attenuates nonalcoholic fatty liver disease through mTOR-mediated inhibition of lipid accumulation and inflammation

Excessive hepatic lipid accumulation and inflammatory injury are significant pathological manifestations of nonalcoholic fatty liver disease (NAFLD). Our previous research discovered that diosgenin, a natural steroidal saponin derived from Chinese herbs, can reduce hepatic lipid accumulation and steatosis; however, the exact mechanism remains unclear. This study aimed to investigate the protective mechanisms of diosgenin against NAFLD. We utilized network pharmacology and molecular docking approaches to identify the pathways through which diosgenin improves NAFLD. In high-fat diet (HFD)-fed rats, we measured biochemical markers in the serum and liver. Liver histopathology was assessed using HE and oil-red O staining. In free fatty acids (FFAs)-induced HepG2 cells, we employed the cell transfection overexpression method to verify the regulatory relationship of the identified pathways. The mechanisms in vitro and in vivo were examined using quantitative polymerase chain reaction and western blot analyses. Bioinformatics analysis indicated that the mTOR-FASN/HIF-1α/RELA/VEGFA pathway may be the target pathway for diosgenin in alleviating NAFLD. Diosgenin inhibited hepatic lipid accumulation and pro-inflammatory cytokines in HFD-fed rats, and reduced intracellular lipid accumulation as well as TG, TC, IL-1β, and TNF-α levels in FFAs-induced HepG2 cells. Mechanistically, diosgenin downregulated the expression of p-mTOR, FASN, HIF-1α, RELA, and VEGFA, which are associated with lipid synthesis and inflammation. Overexpression of mTOR abolished the beneficial effects of diosgenin on lipid reduction and inflammation, as well as its inhibitory effects on the expression of FASN, HIF-1α, RELA, and VEGFA. In conclusion, diosgenin alleviates NAFLD through mTOR-mediated inhibition of lipid accumulation and inflammation.

Effects of compound fermentation of lactic acid bacteria IMAUJBP3 and IMAUJBR3 on the characteristic flavors and metabolites of mutton fermented sausages

Lactobacillus plantarum IMAUJBP3 and Limosilactobacillus reuteri IMAUJBR3 were used to prepare starter cultures. Through the electronic nose (E-nose), it was found that the compound fermentation can enhance the aromatic components in the product. Further analyses using Headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPMEGC–MS) and metabolomics revealed that the complex fermentation affected the oxidative breakdown of amino acids and lipids. HS-SPMEGC-MS identified 72 flavour compounds and found that the Mix group had the highest amount of ester compounds relative to the ZR group. In addition, of the 1402 metabolites identified by metabolomics, dihydroxyacetone phosphate was upregulated and most abundance in the Mix group. Dihydroxyacetone phosphate promotes the metabolism of carbohydrates and lipids, and affects the oxidative decomposition of amino acids and lipids, resulting in differences in flavor among meat products inoculated with different starter cultures. At the same time, it was also found that compound fermentation could down-regulate the compounds affecting product quality such as histamine, putrescine and phenethylamine. Overall, this study found that JBP3 and JBR3 in combination could improve the flavour quality of fermented lamb sausages. These findings may provide a good strain resource for improving the quality of lamb sausage.

Integrative analyses of genetic mechanisms responsible for bone-fat imbalance in osteoporosis.

Osteoporosis manifests through adipocyte accrual and osteoblast diminution within bone marrow. However, the precise mechanisms driving the shift from osteogenesis to adipogenesis in bone marrow mesenchymal stem cells (BMSCs) remain largely undefined. In this study, we harnessed the power of bioinformatic tools to analyze gene expression patterns of BMSCs during adipogenic differentiation and osteoporosis using the data from Gene Expression Omnibus (GEO) repositories (GSE113253 and GSE35956), complemented by in vitro and in vivo experiments to validate the findings. Five distinct expression profiles of differentially expressed genes across the adipogenic timeline were identified. The initial phase is marked by ribosome biogenesis and rRNA processing, which is followed by the metabolism of organic acids and processing of inorganic ions. In contrast, the terminal phase is characterized by lipid transport, accumulation, and metabolism, alongside inorganic cation metabolism, thereby underscoring unique transcriptional signatures during the early and late stages of adipogenic differentiation. In BMSCs derived from osteoporotic samples, there is a notable decline in cellular proliferation and a diminished osteogenic capacity. Critically, the genes common to both adipogenesis and osteoporosis in BMSCs are predominantly involved in the negative regulation of Wnt signaling and cellular proliferation. Key genes including SOCS1, MYC, CEBPB, FYN, AXIN2, and RXRA are identified and show downregulation in BMSCs from aged mice. Subsequent in vitro experiments have validated the regulatory influence of RXRA on both adipogenic and osteogenic differentiations of BMSCs, highlighting its crucial role as a central modulator in bone formation and the pathophysiology of osteoporosis.

Methionine restriction reduced growth performance and exacerbated lipid deposition in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) under high-lipid diets by suppressing the lipid degradation pathways with the single-cell RNA-seq analysis

The experiment mainly focused on the liver of the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) with low methionine levels by single-cell RNA-seq under high-lipid diets. Both weight gain rate (WGR) and specific growth rate (SGR) in the MR group were obviously lower than the C group, and the intraperitoneal fat (IPF) in the MR group was obviously enhanced than HL and C groups, which led to more visible growth inhibition and lipid deposition. By using the scRNA-seq analysis, nine cell types were classified as: liver parenchymal cells, erythrocytes, hepatic stellate cells, cholangiocytes, macrophages, T cells, epidermal cells, eosinophil and fibroblasts. Lipid and carbohydrate metabolisms were mainly enriched in liver parenchymal cells. The lipid degradation pathways were obviously inhibited in the MR group, such as cholesterol degradation pathway. The lipid degradation genes were obviously decreased in the MR group. In conclusion, methionine restriction might suppress the lipid degradation pathways in liver parenchymal cells, led to obvious lipid deposition.