Consequences of the deletion of the major specialized metabolite biosynthetic pathways of Streptomyces coelicolor on the metabolome and lipidome of this strain.

Chassis strains, derived from Streptomyces coelicolor M145, deleted for one or more of its four main specialized metabolites biosynthetic pathways (CPK, CDA, RED and ACT), in various combinations, were constructed for the heterologous expression of specialized metabolites biosynthetic pathways of various types and origins. To determine consequences of these deletions on the metabolism of the deleted strains comparative lipidomic and metabolomic analyses of these strains and of the original strain were carried out. These studies unexpectedly revealed that the deletion of the peptidic clusters, RED and/or CDA, in a strain deleted for the ACT cluster, resulted into a great increase in the triacylglycerol (TAG) content, whereas the deletion of polyketide clusters, ACT and CPK had no impact on TAG content. Low or high TAG content of the deleted strains was correlated with abundance or paucity in amino acids, respectively, reflecting high or low activity of oxidative metabolism. Hypotheses based on what is known on the bio-activity and the nature of the precursors of these specialized metabolites are proposed to explain the unexpected consequences of the deletion of these pathways on the metabolism of the bacteria and on the efficiency of the deleted strains as chassis strains.

The effects of a diet with high fat content from lard on the health and adipose-markers' mRNA expression in mice.

Pork is one type of the most frequently consumed meat with about 30% globally. Thus, the questions regarding to the health effects of diet with high fat content from lard are raised. Here, we developed a model of mice fed with high fat (HF) from lard to investigate and have more insights on the effects of long-time feeding with HF on health. The results showed that 66 days on HF induced a significant gain in the body weight of mice, and this weight gain was associated to the deposits in the white fat, but not brown fat. The glucose tolerance, not insulin resistance, in mice was decreased by the HF diet, and this was accompanied with significantly higher blood levels of total cholesterol and triglycerides. Furthermore, the weight gains in mice fed with HF seemed to link to increased mRNA levels of adipose biomarkers in lipogenesis, including Acly and Acaca genes, in white fat tissues. Thus, our study shows that a diet with high fat from lard induced the increase in body weight, white fat depots' expansion, disruption of glucose tolerance, blood dyslipidemia, and seemed to start affecting the mRNA expression of some adipose biomarkers in a murine model.

The synthesis of triacylglycerol by diacylglycerol acyltransferases (CsDGAT1A and CsDGAT2D) is essential for tolerance of cucumber's resistance to low-temperature stress.

KEY MESSAGE: CsDGAT1A and CsDGAT2D play a positive regulatory role in cucumber's response to low-temperature stress and positively regulate the synthesis of triacylglycerol (TAG). Triacylglycerol (TAG), a highly abundant and significant organic compound in plants, plays crucial roles in plant growth, development, and stress responses. The final acetylation step of TAG synthesis is catalyzed by diacylglycerol acyltransferases (DGATs). However, the involvement of DGATs in cucumber's low-temperature stress response remains unexplored. This study focused on two DGAT genes, CsDGAT1A and CsDGAT2D, investigating their function in enhancing cucumber's low-temperature stress tolerance. Our results revealed that both proteins were the members of the diacylglycerol acyltransferase family and were predominantly localized in the endoplasmic reticulum. Functional analysis demonstrated that transient silencing of CsDGAT1A and CsDGAT2D significantly compromised cucumber's low-temperature stress tolerance, whereas transient overexpression enhanced it. Furthermore, the TAG content quantification indicated that CsDGAT1A and CsDGAT2D promoted TAG accumulation. In conclusion, this study elucidates the lipid metabolism mechanism in cucumber's low-temperature stress response and offers valuable insights for the cultivation of cold-tolerant cucumber plants.

Functional Characterization of the Effects of CsDGAT1 and CsDGAT2 on Fatty Acid Composition in Camelina sativa.

Triacylglycerols (TAGs) are the storage oils of plant seeds, and these lipids provide energy for seed germination and valuable oils for human consumption. Three diacylglycerol acyltransferases (DGAT1, DGAT2, and DGAT3) and phospholipid:diacylglycerol acyltransferases participate in the biosynthesis of TAGs. DGAT1 and DGAT2 participate in the biosynthesis of TAGs through the endoplasmic reticulum (ER) pathway. In this study, we functionally characterized CsDGAT1 and CsDGAT2 from camelina (Camelina sativa). Green fluorescent protein-fused CsDGAT1 and CsDGAT2 localized to the ER when transiently expressed in Nicotiana benthamiana leaves. To generate Csdgat1 and Csdgat2 mutants using the CRISPR/Cas9 system, camelina was transformed with a binary vector carrying Cas9 and the respective guide RNAs targeting CsDGAT1s and CsDGAT2s via the Agrobacterium-mediated floral dip method. The EDD1 lines had missense and nonsense mutations in the CsDGAT1 homoeologs, suggesting that they retained some CsDGAT1 function, and their seeds showed decreased eicosaenoic acid (C20:1) contents and increased C18:3 contents compared to the wild type (WT). The EDD2 lines had a complete knockout of all CsDGAT2 homoeologs and a slightly decreased C18:3 content compared to the WT. In conclusion, CsDGAT1 and CsDGAT2 have a small influence on the seed oil content and have an acyl preference for C20:1 and C18:3, respectively. This finding can be applied to develop oilseed plants containing high omega-3 fatty acids or high oleic acid.

Grape Seed Proanthocyanidin Extract Attenuates Cafeteria-Diet-Induced Liver Metabolic Disturbances in Rats: Influence of Photoperiod.

This study investigated the influence of photoperiod (day length) on the efficacy of grape seed proanthocyanidin extract (GSPE) in mitigating metabolic disorders in obese rats fed a cafeteria diet. Rats were exposed to standard (L12), long (L18), or short (L6) photoperiods and treated with GSPE or vehicle. In the standard photoperiod, GSPE reduced body weight gain (50.5%), total cholesterol (37%), and triglycerides (34.8%), while increasing the expression of hepatic metabolic genes. In the long photoperiod, GSPE tended to decrease body weight gain, increased testosterone levels (68.3%), decreased liver weight (12.4%), and decreased reverse serum amino acids. In the short photoperiod, GSPE reduced glycemia (~10%) and lowered triglyceride levels (38.5%), with effects modified by diet. The standard photoperiod showed the greatest efficacy against metabolic syndrome-associated diseases. The study showed how day length affects GSPE's benefits and underscores considering biological rhythms in metabolic disease therapies.

Macromolecular Interactions of Lipoprotein Lipase (LPL).

Lipoprotein lipase (LPL) is a critical enzyme in humans that provides fuel to peripheral tissues. LPL hydrolyzes triglycerides from the cores of lipoproteins that are circulating in plasma and interacts with receptors to mediate lipoprotein uptake, thus directing lipid distribution via catalytic and non-catalytic functions. Functional losses in LPL or any of its myriad of regulators alter lipid homeostasis and potentially affect the risk of developing cardiovascular disease-either increasing or decreasing the risk depending on the mutated protein. The extensive LPL regulatory network tunes LPL activity to allocate fatty acids according to the energetic needs of the organism and thus is nutritionally responsive and tissue dependent. Multiple pharmaceuticals in development manipulate or mimic these regulators, demonstrating their translational importance. Another facet of LPL biology is that the oligomeric state of the enzyme is also central to its regulation. Recent structural studies have solidified the idea that LPL is regulated not only by interactions with other binding partners but also by self-associations. Here, we review the complexities of the protein-protein and protein-lipid interactions that govern LPL structure and function.

Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Metabolic Changes Induced by Bariatric Surgery May be Mediated by PAI-1 and PCSK9 Crosstalk.

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

The integral role of de novo lipogenesis in the preparation for seasonal dormancy.

Animals can alter their body compositions in anticipation of dormancy to endure seasons with limited food availability. Accumulation of lipid reserves, mostly in the form of triglycerides (TAGs), is observed during the preparation for dormancy in diverse animals, including insects (diapause) and mammals (hibernation). However, the mechanisms involved in the regulation of lipid accumulation and the ecological consequences of failure to accumulate adequate lipid stores in preparation for animal dormancy remain understudied. In the broadest sense, lipid reserves can be accumulated in two ways: the animal either receives lipids directly from the environment or converts the sugars and amino acids present in food to fatty acids through de novo lipogenesis and then to TAGs. Here, we show that preparation for diapause in the Colorado potato beetle (Leptinotarsa decemlineata) involves orchestrated upregulation of genes involved in lipid metabolism with a transcript peak in 8- and 10-d-old diapause-destined insects. Regulation at the transcript abundance level was associated with the accumulation of substantial fat stores. Furthermore, the knockdown of de novo lipogenesis enzymes (ACCase and FAS-1) prolonged the preparatory phase, while the knockdown of fatty acid transportation genes shortened the preparatory phase. Our findings suggest a model in which the insects dynamically decide when to transition from the preparation phase into diapause, depending on the progress in lipid accumulation through de novo lipogenesis.

Lipophilic and Hydrophilic Metabolites as Descriptors of Different Coffee Beverages.

Coffee is a widely consumed beverage rich in bioactive phytochemicals. This study investigated the effect of brewing method on the profile of potential bioactive compounds in different coffee beverages using metabolomics and lipidomics based on UHPLC-MS/QTOF. The oil contents of the espresso coffee (EC), pot coffee (PC), instant coffee (IC), and filter coffee (FC) beverages studied were 0.13% ± 0.002, 0.12% ± 0.001, 0.04% ± 0.002, and 0.03% ± 0.003, respectively. Univariate analysis indicated significant differences (P < 0.001) in oil content when EC and PC beverages were compared with IC and FC beverages. Principal component analysis revealed similarities in the lipid profiles of FC and EC beverages and the hydrophilic profiles of PC and FC beverages. The EC beverage had the highest intensity of hydrophilic compounds such as adenine, theobromine, chlorogenic acid, and caffeine. The PC beverage was the most abundant in triglycerides, phosphatidylcholine, and diterpenes. Cafestol and kahweol esters, but not their free forms, were the most abundant diterpenes in the PC beverage. This work provides information on the differences in the profile of potentially bioactive compounds in four commonly consumed coffee beverage types and, thus, on the possible differences in the health effects of these coffee beverage types.

Bta-miR-200a Regulates Milk Fat Biosynthesis by Targeting IRS2 to Inhibit the PI3K/Akt Signal Pathway in Bovine Mammary Epithelial Cells.

Milk fat synthesis has garnered significant attention due to its influence on the quality of milk. Recently, an increasing amount of proofs have elucidated that microRNAs (miRNAs) are important post-transcriptional factor involved in regulating gene expression and play a significant role in milk fat synthesis. MiR-200a was differentially expressed in the mammary gland tissue of dairy cows during different lactation periods, which indicated that miR-200a was a candidate miRNA involved in regulating milk fat synthesis. In our research, we investigated the potential function of miR-200a in regulating milk fat biosynthesis in bovine mammary epithelial cells (BMECs). We discovered that miR-200a inhibited cellular triacylglycerol (TAG) synthesis and suppressed lipid droplet formation; at the same time, miR-200a overexpression suppressed the mRNA and protein expression of milk fat metabolism-related genes, such as fatty acid synthase (FASN), peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), CCAAT enhancer binding protein alpha (CEBPα), etc. However, knocking down miR-200a displayed the opposite results. We uncovered that insulin receptor substrate 2 (IRS2) was a candidate target gene of miR-200a through the bioinformatics online program TargetScan. Subsequently, it was confirmed that miR-200a directly targeted the 3'-untranslated region (3'-UTR) of IRS2 via real-time fluorescence quantitative PCR (RT-qPCR), western blot analysis, and dual-luciferase reporter gene assay. Additionally, IRS2 knockdown in BMECs has similar effects to miR-200a overexpression. Our research set up the mechanism by which miR-200a interacted with IRS2 and discovered that miR-200a targeted IRS2 and modulated the activity of the PI3K/Akt signaling pathway, thereby taking part in regulating milk fat synthesis in BMECs. Our research results provided valuable information on the molecular mechanisms for enhancing milk quality from the view of miRNA-mRNA regulatory networks.

Studying microbial triglyceride production from corn stover saccharides unveils insights into the galactose metabolism of Ustilago maydis.

The global demand for plant oil has reached unprecedented levels and is relevant in all industrial sectors. Driven by the growing awareness for environmental issues of traditional plant oils and the need for eco-friendly alternatives, microbial oil emerges as a promising product with significant potential. Harnessing the capabilities of oleaginous microorganisms is an innovative approach for achieving sustainable oil production. To increase economic feasibility, it is crucial to explore feedstocks such as agricultural waste streams as renewable resource for microbial bioprocesses. The fungal model Ustilago maydis is one promising organism in the field of microbial triglyceride production. It has the ability to metabolize a wide variety of carbon sources for cell growth and accumulates high amounts of triglycerides intracellularly. In this study we asked whether this large variety of usable carbon sources can also be utilized for triglyceride production, using corn stover saccharides as a showcase.Our experiments revealed metabolization of the major saccharide building blocks present in corn stover, demonstrating the remarkable potential of U. maydis. The microorganism exhibited the capacity to synthesize triglycerides using the saccharides glucose, fructose, sucrose, xylose, arabinose, and galactose as carbon source. Notably, while galactose has been formerly considered as toxic to U. maydis, we found that the fungus can metabolize this saccharide, albeit with an extended lag phase of around 100 hours. We identified two distinct methods to significantly reduce or even prevent this lag phase, challenging previous assumptions and expanding the understanding of U. maydis metabolism.Our findings suggest that the two tested methods can prevent long lag phases on feedstocks with high galactose content and that U. maydis can produce microbial triglycerides very efficiently on many different carbon sources. Looking forward, exploring the metabolic capabilities of U. maydis on additional polymeric components of corn stover and beyond holds promise for innovative applications, marking a significant step toward environmentally sustainable bioprocessing technologies.

Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis.

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (-Fe). Cells grown in -Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.

Massive stocking of chum salmon (Oncorhynchus keta) fry fattens non-native brown trout (Salmo trutta) in Hokkaido, Japan.

In Japan, stocked chum salmon (Oncorhynchus keta) fry may have become the perfect prey for non-native brown trout (Salmo trutta), which are popular targets of anglers. If this is the case, fry stocking which is intended to boost commercial fishing may be helping to sustain the populations of an invasive predator. We used dietary and biochemical analyses to examine whether brown trout quickly restore their nutritional status following wintertime declines by preying upon chum salmon fry that are stocked in spring. We targeted six rivers in Hokkaido, Japan, three with fry stocking and three without. Changes in brown trout condition factor, triglyceride contents in muscle and serum, serum insulin-like growth factor-1 (IGF-1; an indicator of short-term growth), and docosahexaenoic acid (DHA; an essential fatty acid abundant in fish) content in muscle were examined between before stocking and during the stocking period in the six rivers. Dietary analysis showed that brown trout preyed on fry during the stocking period in all stocked rivers. Their nutritional status tended to be higher during the stocking period than before stocking in stocked rivers, but not in unstocked rivers. These results suggest that the massive stocking of chum salmon fry provides brown trout with the perfect prey to quickly restore their nutritional status and fuel increased growth; this may therefore be a controversial issue among stakeholders.

Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression.

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid ß-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased de novo lipogenesis and fatty acid ß-oxidation, but increased lipolysis. These changes lead to elevated free fatty acids and reduced triglyceride (TG) accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes TG accumulation in both larval and adult adipocytes. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Taken together, these findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid ß-oxidation.

The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice.

BACKGROUND: In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood. METHODS: Using deuterated water, we measured DNL in mice fed 18-weeks with standard chow (SC), SC supplemented with 55/45-fructose/glucose in the drinking water at 30% (w/v) (HS), high-fat chow (HF), and HF with HS supplementation (HFHS). Liver glycogen levels and its sources were also measured. For HS and HFHS mice, pentose phosphate (PP) fluxes and fructose contributions to DNL and glycogen were measured using [U-13C]fructose. RESULTS: The lipogenic diets caused significantly higher liver triglyceride levels compared to SC. DNL rates were suppressed in HF compared to SC and were partially restored in HFHS but supplied a minority of the additional triglyceride in HFHS compared to HF. Fructose contributed a significantly greater fraction of newly synthesized saturated fatty acids compared to oleic acid in both HS and HFHS. Glycogen levels were not different between diets, but significant differences in Direct and Indirect pathway contributions to glycogen synthesis were found. PP fluxes were similar in HS and HFHS mice and were insufficient to account for DNL reducing equivalents. CONCLUSIONS: Despite amplifying the lipogenic effects of fat, the fact that sugar-activated DNL per se barely contributes suggests that its role is likely more relevant in the inhibition of fatty acid oxidation. Fructose promotes lipogenesis of saturated over unsaturated fatty acids and contributes to maintenance of glycogen levels. PP fluxes associated with sugar conversion to fat account for a minor fraction of DNL reducing equivalents.

Impaired Fat Absorption from Intestinal Tract in High-Fat Diet Fed Male Mice Deficient in Proglucagon-Derived Peptides.

(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p < 0.05), and Pparα (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Pparα and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced ß-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.

Quinoa Polyphenol Extract Alleviates Non-Alcoholic Fatty Liver Disease via Inhibiting Lipid Accumulation, Inflammation and Oxidative Stress.

Recently, the incidence of NAFLD has exploded globally, but there are currently no officially approved medications for treating the condition. The regulation of NAFLD through plant-derived active substances has become a new area of interest. Quinoa (Chenopodium quinoa Willd.) has been discovered to contain a large quantity of bioactive compounds. In this study, we established a free fatty acid (FFA)-induced steatosis model and explored the effects of quinoa polyphenol extract (QPE) on the major hallmarks of NAFLD. The results indicated that QPE significantly reduced intracellular triglyceride (TG) and total cholesterol (TC) levels. Additionally, QPE remarkably elevated the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) and lowered levels of malondialdehyde (MDA). Further examination revealed that QPE attenuated intracellular inflammation, which was verified by the reduced levels of pro-inflammatory cytokines. Mechanistically, QPE inhibited fatty acid biosynthesis mainly by targeting de novo lipogenesis (DNL) via the AMPK/SREBP-1c signaling pathway. Moreover, network pharmacology was used to analyze key targets for NAFLD mitigation by ferulic acid (FA), a major component of QPE. Taken together, this study suggests that QPE could ameliorate NAFLD by modulating hepatic lipid metabolism and alleviating oxidative stress and inflammation.

Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study.

BACKGROUND: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients. METHODS: This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis. RESULTS: 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), p < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, p < 0.001) and hospital (OR range 1.068-1.445, p = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (p = 0.014, 0.016, and < 0.001, respectively). CONCLUSION: TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.