G-protein coupled receptors (GPCR) are one of the frequently investigated drug targets. GPCRs are involved in many human pathophysiologies that lead to various disease conditions, such as cancer, diabetes, and obesity. GPCR receptor activates multiple signaling pathways depending on the ligand and tissue type. However, this review will be limited to the GPCR-mediated metabolic modulations and the activation of relevant signaling pathways in cancer therapy. Cancer cells often have reprogrammed cell metabolism to support tumor growth and metastatic plasticity. Many aggressive cancer cells maintain a hybrid metabolic status, using both glycolysis and mitochondrial metabolism for better metabolic plasticity. In addition to glucose and glutamine pathways, fatty acid is a key mitochondrial energy source in some cancer subtypes. Recently, targeting alternative energy pathways like fatty acid beta-oxidation (FAO) has attracted great interest in cancer therapy. Several in vitro and in vivo experiments in different cancer models reported encouraging responses to FAO inhibitors. However, due to the potential liver toxicity of FAO inhibitors in clinical trials, new approaches to indirectly target metabolic reprogramming are necessary for in vivo targeting of cancer cells. This review specifically focused on free fatty acid receptors (FFAR) and β-adrenergic receptors (β-AR) because of their reported significance in mitochondrial metabolism and cancer. Further understanding the pharmacology of GPCRs and their role in cancer metabolism will help repurpose GPCR-targeting drugs for cancer therapy and develop novel drug discovery strategies to combine them with standard cancer therapy to increase anticancer potential and overcome drug resistance.

This study investigated the effects of dietary short-chain fatty acid (SCFA) supplementation, on growth performance, metabolism, and antioxidant status of European seabass juveniles. Six isoproteic (43 % crude protein) and isolipidic (18 % crude lipid) diets were formulated to include 0.25 and 0.50 % Sodium acetate (SA), Sodium propionate (SP), or Sodium butyrate (SB). A diet without SCFA supplementation was used as a control. The diets were fed to triplicate groups of European seabass juveniles (initial body weight of 15 g) for 56 days. The supplementation of SCFA in the diet had no impact on the growth, feed utilization, or body composition of seabass. In the intestine, gene expression of pyruvate kinase (pk) and glucokinase (gk), phosphoenolpyruvate carboxykinase (pepck), glucose facilitative carrier type 2 (glut2), and citrate synthase (cs) was lower in fish fed the SP0.50 diet than in the other groups. Moreover, fatty acid synthase (fas) gene expression was lower in fish fed the SA0.25, SA0.50, and SB0.25 diets than in the other groups. Further, catalase (CAT) and glutathione reductase (GR) activity and lipid peroxidation (LPO) levels showed no differences between groups. In contrast, glutathione peroxidase (GPX) activity was higher in fish fed the SP0.50 diet. In the liver, GR activity and LPO levels showed no differences between groups. In contrast, CAT activity was lower in all dietary treatments than in control, and GPX and G6PDH activity was lower in fish fed with the SB (0.25 and 0.50 %) diet than in the other diets. Overall, SCFA supplementation did not affect growth performance and feed utilization and only had minor effects on metabolism and antioxidant defense mechanisms.

Butyrate is a four-carbon short-chain fatty acid produced from microbial fermentation of dietary fibers present at high millimolar concentrations in the colonic lumen. However, in an intact epithelium, macrophages residing in the lamina propria are exposed to only micromolar butyrate concentrations. Current studies show anti-inflammatory properties of butyrate and suggest that it might have therapeutic applications in inflammatory bowel disease and colonic cancer. We now show that the effect of butyrate on human macrophages is strongly concentration dependent: 0.1 mM butyrate suppresses LPS-induced production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. Experiments with siRNA knockdown and small molecule inhibitors suggest that this is mediated by a mechanism involving PPAR-γ signaling, whereas we observed no or only a minor effect of histone acetylation. In contrast, 10 mM butyrate promotes macrophage cell death, does not inhibit LPS-induced production of TNF-α, and promotes production of IL-1β, while production of anti-inflammatory IL-10 is reduced in a mechanism involving G protein-coupled receptors, the lipid transporter CD36, and the kinase SRC. We propose that butyrate is a signaling molecule for intestinal integrity, since intestinal disruption exposes macrophages to high butyrate concentrations.

Fat composition of milk replacer (MR) for calves differs from that of bovine milk fat, resulting in lower levels of butyric (C4:0) and caproic acid (C6:0). These fatty acids play a critical role in the gastrointestinal and metabolic development of calves by supporting rumen epithelial growth, enhancing energy metabolism, and promoting overall gut health. The objective of this study was to evaluate the effects of inclusion of a spray-dried fat concentrate containing tributyrin (TB) and tricaproin (TC) in a high-fat MR on growth, feed intake, and metabolic profiles of ad libitum-fed calves. Forty-eight newborn Holstein calves were blocked based on arrival sequence. Within each block of 2 calves, calves were randomly assigned to a control MR (CON, n = 24) including vegetable fats from palm, coconut, and linseed fats, or to an experimental MR including the same fat blend, to which TB and TC (TRI, n = 24) was added to the same levels found in milk fat. Both MR contained 23.7% crude protein, 27.7% fat, and 35.6% lactose (DM basis) and were fed at 13.5% solids. Calves were group housed and fed ad libitum MR with automated feeders. Weaning was gradual and induced between wk 7-10, after which calves were only fed solid feeds. Starter feed, chopped straw, and water were offered ad libitum throughout the whole study period. Calves were weighed and blood was collected once weekly at 1300h. Calves fed TRI showed a ∼50% reduction in therapeutic intervention days compared with CON. In addition, calves fed TRI consumed significantly more MR and starter feed, resulting in a greater growth. Serum NEFA and plasma total cholesterol were lower, whereas the enzymatic activity of serum ALP was higher in calves fed TRI than in CON. In addition, calves fed TRI had lower serum ghrelin and higher insulin-like growth factor-I concentrations. Incorporating TB and TC is a suitable strategy to increase solid feed intake upon weaning, resulting in better growth performance in ad libitum systems, and to improve health of dairy rearing calves.

Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). β-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms.

This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship.

Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk.

Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

Type 2 diabetes is an inflammatory, non-infectious disease characterized by dysfunctional pancreatic β-cells and insulin resistance. Although lifestyle, genetic, and environmental factors are associated with a high risk of type 2 diabetes, nutrition remains one of the most significant factors. Specific types and increased amounts of dietary fatty acids are associated with type 2 diabetes and its complications. Dietary recommendations for the prevention of type 2 diabetes advocate for a diet that is characterized by reduced saturated fatty acids and trans fatty acids alongside an increased consumption of monounsaturated fatty acids, polyunsaturated fatty acids, and omega-3 fatty acids. Although following the recommendations for dietary fatty acid intake is important for reducing type 2 diabetes and its related complications, the underlying mechanisms remain unclear. This review will provide an update on the mechanisms of action of fatty acids on glucose metabolism and type 2 diabetes, as well as dietary recommendations for the prevention of type 2 diabetes.

Infancy is a vulnerable and critical phase in the acquisition of the gut microbiome and the establishment of immune function. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are compounds mostly produced by the microbiome through various metabolic pathways and play an indispensable role in connecting the microbiome and the adaptive immune system. This review aims to summarise recent findings regarding the intricate relationship between SCFAs, the gut microbiome, and T lymphocytes with a focus on early life interactions. The paper discusses factors affecting the establishment of the neonatal microbiome, especially human milk versus formula milk, and how these influence SCFA concentrations in feces, which in turn directly impact T cell development and function. Despite recent advances in understanding the role of gut microbiome derived SCFAs in adults, a significant knowledge gap remains in translating these findings to neonates and exploring the utility of SCFAs as a potential therapeutic intervention in inflammatory complications of preterm and term neonates. IMPACT: This review highlights potential therapeutic applications of short-chain fatty acids (SCFAs) in neonatal care, particularly in preventing and treating inflammatory conditions. This could lead to new treatment strategies for conditions like NEC and other immune-mediated disorders in neonates. By identifying significant knowledge gaps in neonatal SCFA research, this review helps future investigations toward understanding SCFA mechanisms specifically in neonates, potentially leading to age-appropriate therapeutic interventions. Understanding the relationship between early-life factors (such as feeding methods and microbiome development) and immune system development through SCFAs could inform public health policies and recommendations for infant nutrition and care practices.

Medium-chain fatty acids (MCFAs) refer to a mixture of fatty acids typically composed of 6 to 12 carbon atoms. The unique transport and rapid metabolism of MCFAs provide more clinical benefits than other substrates, such as long-chain fatty acids. Although many studies have shown that MCFAs may improve exercise capacity and muscle strength, applications have mainly been limited to low doses. This study explores the effects of high-dose MCFA intake on muscle strength and exercise endurance. Mice were fed high-fat diets containing 30, 35, and 40% (w/w) MCFAs for 12 weeks, and measurements of grip strength and submaximal endurance exercise capacity were conducted to evaluate muscle function. Results showed that compared to the 30% MCFAs group, the absolute grip strength in the 35 and 40% MCFAs groups significantly increased; in terms of endurance performance, the 35% MCFAs group showed a significant increase compared to the 40% MCFAs group. These results were mainly achieved by promoting muscle regeneration and differentiation and inhibiting the expression of the ubiquitin-proteasome pathway. This study demonstrates that moderately increasing MCFA intake can improve the effects of obesity-induced muscle atrophy. However, excessive intake may reduce the impact of improvement.

The n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have a key role in maintaining fish growth and health. However, fish oil (FO), the main source of n-3 LC-PUFAs, is in relative shortage due to the rapid development of the aquaculture industry. In this study, we investigated the efficacy of replacing fish oil with mixtures of algal oil (AO) from Schizochytrium sp. and terrestrially sourced oils (animal oil poultry oil (PO) or vegetable oil rapeseed oil (RO)) in the diets of juvenile tiger puffer (average initial body weight 23.8 ± 1.51 g). An 8-week feeding trial was conducted using three experimental diets: a control diet containing 6% added FO (control FO-C) and two diets with 3% AO + 3% PO or RO (groups AO+PO and AO+RO, respectively), replacing FO. Each diet was fed to triplicate tanks with 25 fish in each tank. The weight gain, feed conversion ratio, body composition, and serum biochemical parameters were not significantly different among the three groups, except that the AO+PO group had a significantly lower muscle lipid content than the other two groups. The AO-added diets significantly increased the DHA content in whole fish, muscle, and liver samples but significantly reduced the EPA content. The oil mixture treatments significantly increased the contents of monounsaturated fatty acid (MUFA) but significantly decreased the contents of saturated fatty acids (SFAs) in the liver and whole fish samples. However, the MUFA and SFA contents in the muscle samples were not significantly different among the dietary groups. The diets with oil mixtures did not affect the hepatic histology but tended to result in the atrophy of intestinal villi. The treatment diets downregulated the hepatic gene expression of proinflammatory cytokines (il-1β and tnf-α) and the fibrosis marker gene, acta2. However, the AO+PO diet inhibited the intestinal gene expression of the tight junction protein, claudin 18. In the muscle, the treatment diets upregulated the expression of genes related to cell differentiation and apoptosis (myod, myog, myf6, myf5, bcl-2, and bax). In conclusion, Schizochytrium sp. oil in combination with terrestrial oils (poultry oil or rapeseed oil) can be an effective alternative to fish oil in the diets of tiger puffer, but the mixing strategy may be better modified in consideration of intestinal health.

The importance of fatty acids in human health and their potential in treating various brain diseases is increasingly acknowledged. Research indicates that ultra-long-chain fatty acids adversely affect dietary habits, while omega (ω)-3 polyunsaturated fatty acids confer health benefits. Eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, manifests diverse protective activities, including anti-oxidative effects and the attenuation of brain diseases. Previous studies have suggested that EPA can alleviate oxidative stress and forestall diseases stemming from oxidative damage. Nevertheless, EPA's precise antioxidant mechanism and signaling pathway in human astrocytes remain elusive. To address this knowledge gap, we established an H2O2-induced oxidative damage model in Gibco® Human Astrocytes (GHA cells) and elucidated the underlying mechanisms and signaling pathways.

Our assessments included cell viability through the CCK-8 assay, morphological examination via microscopy, ROS quantification using the DCFH-DA fluorescent probe, GSH content evaluation with the CMF-DA fluorescent probe, and protein expression analysis for antioxidant and apoptotic markers through Western blotting. The results showed that pretreatment with 3 µM of EPA countered the cytotoxicity, ROS production, and GSH depletion caused by H2O2 (250 µM) in GHA cells. Additionally, EPA pretreatment effectively reduced the cytotoxicity and oxidative stress resulting from H2O2 by modulating the Nrf2/HO-1/NQO1 and Bax/Bcl-2/caspase-9/caspase-3 signaling pathways in GHA cells.

These findings enhance our understanding of EPA's antioxidant mechanisms in the oxidative stress model of human astrocytes, illuminate the interplay between antioxidant and apoptotic signals, and offer promise for exploring potential preventive and therapeutic interventions for brain diseases.

The present study aimed to investigate the effects of exogenous carnitine treatments on maize seed germination by stimulating lipid metabolism and regulating the mitochondrial respiratory pathway. Maize seeds were grown as control, 5, 7.5, and 10 μM carnitine treatment groups in a germination chamber at 25 °C under dark conditions for 5 d. It was determined that carnitine treatments increased the germination rate (GR), germination index (GI), germination potential (GP), vigor index (VI), root and hypocotyl length, fresh weight (FW), and content of total soluble protein but decreased the total carbohydrate content. It was also found that it increased the activities of α-amylase, isocitrate lyase (ICL), and malate synthase (MS) enzymes, which are critical in the germination process, and upregulated the expression of ICL and MS genes. To clarify the potential of carnitine treatments to promote the participation of lipids in respiration in roots and hypocotyls, lipase, carnitine acyltransferases (CATI and CATII), and citrate synthase (CS) enzyme activities were examined, and significant increases in these activities were detected. It was also found that gene levels of respiratory enzymes cytochrome oxidase (COX), pyruvate dehydrogenase (PDH), and Atp synthase, lipase, and CS proteins were upregulated by carnitine treatment. In support of the enzyme and gene change findings, significant changes were determined in fatty acid contents, free carnitine, and long-chain acylcarnitine levels in seeds, roots, and hypocotyls depending on carnitine application. In roots and hypocotyls, carnitine treatments significantly increased glutamine synthase (GS) and glutamate dehydrogenase (NADH-GDH) activities and gene expression levels, which are closely related to the tricarboxylic acid cycle (TCA). It was also noted that all proteins analyzed at the gene expression level were upregulated by carnitine applications in seeds. In addition, significant increases were recorded in antioxidant enzyme ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities and total ascorbate (AsA) and glutathione (GSH) contents in roots and hypocotyls, while decreases were determined in guaiacol peroxidase (GPX) and catalase activities. Significant changes were recorded in all parameters examined, especially with 7.5 µM carnitine application. The findings suggest that carnitine may promote the transport of fatty acids to mitochondrial respiration by accelerating lipid catabolism in five-day-old maize and contribute to seed germination and growth and development processes by activating other metabolic pathways associated with respiration in this process.

Non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and has become the greatest potential risk for cirrhosis and hepatocellular carcinoma. The metabolites produced by the gut microbiota act as signal molecules that mediate the interaction between microorganisms and the host and have biphasic effects on human health. The gut microbiota and its metabolites, short-chain fatty acids (SCFAs), have been discovered to ameliorate many prevalent liver diseases, including NAFLD. Currently, SCFAs have attracted widespread attention as potential therapeutic targets for NAFLD, but the mechanism of action has not been fully elucidated. This article summarizes the mechanisms of short-chain fatty acids of gut microbiota metabolites to regulate the metabolism of glucose and lipid, maintain the intestinal barrier, alleviate the inflammatory response, and improve the oxidative stress to improve NAFLD, in order to provide a reference for clinical application.

Feeding low crude protein (LCP) diets supplemented with crystalline amino acids improves environmental and welfare parameters of broilers. However, increased body fat contents in broilers fed LCP diets have become a concern. Black soldier fly larvae oil (BSFLO), rich in lauric acid, has been reported to inhibit lipogenesis and reduce body fat. A 3 × 2 factorial experiment was conducted to evaluate the effect of BSFLO on performance, blood biochemistry, carcass quality, fat metabolism gene expression, and litter quality in broilers fed protein-reduced diets. A total of 288 broilers were divided into 6 treatments: three CP levels (200, 185, or 170 g/kg; high [HCP], medium [MCP], or low [LCP]) and two oil sources (BSFLO and Crude Palm Oil [CPO]), with 6 replicate pens of 8 birds each. Results showed a 15 g/kg CP reduction had no effect on body weight and feed intake (P > 0.05) but increased FCR (P = 0.001). A 30 g/kg CP significantly reduced the body weight and feed intake with inferior FCR (P < 0.05). However, negative effect of low CP diets on FCR was mitigated by BSFLO (P = 0.008). Reducing CP by 30 g/kg increased fat pads (P = 0.033), whereas BSFLO reduced fat pads (P = 0.049) at all three CP levels. Protein-reduced diets increased blood cholesterol (P = 0.002), HDL (P < 0.001), and LDL (P = 0.002). BSFLO decreased blood triglyceride (P = 0.026) and cholesterol (P < 0.001). Reducing 30 g/kg CP increased meat cooking loss (P = 0.035), while BSFLO decreased cooking loss (P < 0.001). BSFLO increased meat protein (P < 0.001) and decreased cholesterol (P = 0.003). The inclusion of BSFLO in protein-reduced diet down-regulated the gene expression of FAS, ACC, SREBP-1, and HMGR in broilers (P < 0.001). Reducing CP levels decreased litter pH (P = 0.011), nitrogen (P < 0.001), ammonia (P < 0.001) and moisture (P = 0.018). The study concludes that BSFLO reduced body fat by down-regulating the lipogenesis gene expression. In addition, BSFLO enhanced feed efficiency in broilers fed protein-reduced diet.

The potential of insects as alternative ingredients in animal feeds is well-established. However, limited information is available on the use of insect oils as alternative lipid sources in aquafeeds. To address this, a study was conducted on gilthead seabream (Sparus aurata) juveniles to evaluate the effects of including black soldier fly (Hermetia illucens) larvae oil (HIO). Diets were formulated to include 4, 7.9, and 9.5 % HIO, replacing a vegetable oil blend at 42, 84, or 100 %, respectively. After 70 days, the effects on liver fatty acid profiles, plasma metabolites, and lipid metabolism gene expression were assessed. The results showed that HIO inclusion led to a linear decrease in plasma lipids and triglycerides, while high-density lipoprotein levels increased. The experimental diets also altered the liver's fatty acid composition without affecting total lipid content. There was an increase in the liver's saturated fatty acid content, like lauric acid, and monounsaturated fatty acids, like oleic acid. In contrast, n-3 and n-6 polyunsaturated fatty acid content was reduced, although EPA and DHA levels remained unaffected. Additionally, the content of C16:0 and C18:0 (% of total fatty acids) was higher in the liver than in the corresponding diets. The inclusion of HIO had minimal impact on the expression of genes associated with fatty acid synthesis, transport, and β-oxidation. However, a downregulation of elongation of very long-chain fatty acids proteins 6 and 1b (elovl6 and elovl1b) was observed with increasing HIO levels. Overall, the study indicates that up to 9.5 % HIO inclusion in diets is well tolerated by gilthead seabream juveniles, with minimal effects on plasma metabolites and key gene expression related to fatty acid metabolism. These findings support the use of HIO as a viable alternative lipid source for juvenile gilthead seabream, contributing to the sustainable development of aquafeeds.

Endometriosis affects about 10 % of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.

The ketogenic diet (KD) is a dietary regimen characterized by low carbohydrate intake and moderate protein levels, designed to simulate a fasting state and induce ketosis for the production of ketone bodies from fat. Emerging research underscores KD's potential in improving cognitive functions and regulating mood. Investigations into its safety and efficacy have centered on its anti-inflammatory properties and its impact on neurological health and the gut-brain axis (GBA). This review delves into the relationship between the KD and gut microbiota, emphasizing its potential role in cognitive enhancement and mood stabilization, particularly for managing mood disorders and depression. The investigation of the KD's physiological effects and its role in promoting cognition and emotion through gut microbiota will pave the way for innovative approaches to personalized dietary interventions.

This study aims to explore the characteristics and functional changes of intestinal metabolites in children with obstructive sleep apnea hypopnea syndrome (OSAHS) aged 4-6 years old through metabolomic approaches, screen potential biomarkers and analyze their correlation with clinical indicators and preliminary discuss the roles of intestinal metabolites in the occurrence and development of OSAHS.

We collected fecal samples from 40 OSAHS children and 40 healthy controls aged 4-6 years and recorded some OSAHS-related clinical indicators. Fecal specimens were used to detect all metabolites through untargeted metabolomics.

This study identified a total of 1164 intestinal metabolites and screened out 254 differential metabolites. In the OSAHS group, the relative content of 96 metabolites were higher than the control group, while the relative content of 158 metabolites were lower. The receiver operating characteristic curve analysis results showed that the area under the curve of 14 differential metabolites was greater than 0.8. The area under the curve of Formononetin is the highest, at 0.9100, with sensitivity and specificity of 82.5% and 90.0%, respectively, and is positively correlated with OAHI. The differential metabolite functions mainly include the metabolism of fatty acids and other lipid substances, cellular signaling, protein and amino acid related metabolism, disease-related functions, glucose metabolism, and vitamin metabolism.

The intestinal metabolites and metabolic function of 4-to-6-year-old children with OSAHS altered. There was a correlation between differential metabolites and clinical indicators such as uric acid, hemoglobin, and blood sugar, which has potential diagnostic value for OSAHS screening.

Traditionally, the carnitine pool is closely related to fatty acid metabolism. However, with increasing research, the pleiotropic effects of the carnitine pool have gradually emerged. The purpose of this review is to comprehensively investigate of the emerging understanding of the pleiotropic role of the carnitine pool, carnitine/acylcarnitines are not only auxiliaries or metabolites of fatty acid oxidation, but also play more complex and diverse roles, including energy metabolism, mitochondrial homeostasis, epigenetic regulation, regulation of inflammation and the immune system, tumor biology, signal transduction, and neuroprotection. This review provides an overview of the complex network of carnitine synthesis, transport, shuttle, and regulation, carnitine/acylcarnitines have the potential to be used as communication molecules, biomarkers and therapeutic targets for multiple diseases, with profound effects on intercellular communication, metabolic interactions between organs and overall metabolic health. The purpose of this review is to comprehensively summarize the multidimensional biological effects of the carnitine pool beyond its traditional role in fatty acid oxidation and to summarize the systemic effects mediated by carnitine/acylcarnitine to provide new perspectives for pharmacological research and treatment innovation and new strategies for the prevention and treatment of a variety of diseases.

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulated renal PPARα signaling and restored FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing showed that renal metabolic pathways were impaired in Alport mice and activated by NR in both sexes. These transcriptional changes were confirmed by orthogonal imaging techniques and biochemical assays. Single-nuclei RNA sequencing and spatial transcriptomics, both the first of their kind to our knowledge from Alport mice, showed that NAD+ supplementation restored FAO in proximal tubule cells. Finally, we also report, for the first time to our knowledge, sex differences at the transcriptional level in this Alport model. In summary, the data herein identify a nephroprotective mechanism of NAD+ supplementation in CKD, and they demonstrate that this benefit localizes to the proximal tubule cells.

This study evaluated the effect of maternal glycerol monolaurate (GML) supplementation during late gestation and lactation on sow reproductive performance, transfer of immunity and redox status, milk fat and fatty acid profile, and fecal microbiota. Eighty multiparous sows (Landrace × Large white) were randomly allocated to two treatment groups (with or without 1000 mg/kg GML) with 40 replicates per treatment. The feeding experiment lasted from d 85 of gestation (G85) to d 23 of lactation (L23). The samples were collected on d 1 (L1) and 21 (L21) of lactation. Our results showed that maternal GML supplementation significantly increased litter weight (P = 0.002), average daily gain of piglets (P = 0.048), and sow average daily feed intake (P = 0.032). Compared with CON group, the concentrations of lauric acid (C12:0; P = 0.022), C16:0 (P = 0.001), and total saturated fatty acids (P = 0.006) in colostrum as well as C12:0 in L21 milk (P = 0.001) were higher in GML group. Besides, the concentrations of immunoglobulin A (IgA) and IgG in colostrum as well as sow and piglet plasma, the total antioxidant capacity and superoxide dismutase activity in sow colostrum were also significantly higher in the GML group (P < 0.05). Microbiome results showed that GML addition increased fecal microbial alpha diversity as well as the relative abundances of short chain fatty acids producing bacteria Ruminococcaceae and Parabacteroides; and decreased the harmful Proteobacteria of sows (P < 0.05). The Spearman analysis showed that the microbial biomarkers Prevotellaceae, Ruminococcaceae, and Parabacteroides were positively correlated with IgA and IgG of sow plasma and milk (P < 0.05). Besides, maternal GML addition up-regulated the relative protein expressions of proliferating cell nuclear antigen, cyclin D1, G protein-coupled receptor 84 (GPR84) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in the duodenum and jejunum of piglets. Collectively, current findings suggested that maternal GML supplementation enhanced piglet growth during lactation, which might be associated with improving milk fat and lauric acid contents, microbiota derived immunoglobulins transfer, and gut health through potential involvement of GPR84 and PI3K/Akt signaling pathway.

Viral infections can cause cellular pathway derangements, cell death, and immunopathological responses, leading to host inflammation. Short-chain fatty acids (SCFAs), produced by the microbiota, have emerged as a potential therapeutic for viral infections due to their ability to modulate these processes. However, SCFAs have been reported to have both beneficial and detrimental effects, necessitating a comprehensive understanding of the underlying mechanisms. This review highlights the complex mechanisms underlying SCFAs' effects on viral infection outcomes. We also emphasize the importance of considering how SCFAs' activities may differ under diverse contexts, including but not limited to target cells with different metabolic wiring, different viral causes of infection, the target organism/cell's nutrient availability and/or energy balance, and hosts with varying microbiome compositions.

Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope labelling with [U-13C]butyrate and [1,2-13C]acetate to map metabolism via mass spectrometry. Metabolic competition assays in cerebral cortical slices revealed no competition between butyrate and the ketone body, β-hydroxybutyrate, but competition with acetate. Astrocytes favoured butyrate metabolism compared to neurons, suggesting that the astrocytic compartment is the primary site of butyrate metabolism. In-vivo metabolism investigated in the 5xFAD mouse, an AD pathology model, showed no difference in 13C-labelling of TCA cycle metabolites between wild-type and 5xFAD brains, but butyrate metabolism remained elevated compared to acetate in both groups, indicating sustained uptake and metabolism in 5xFAD mice. Overall, these findings highlight the role of astrocytes in butyrate metabolism and the potential use of butyrate as an alternative brain fuel source.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

Oral administration of acetic acid, a short-chain fatty acid, has been shown to efficiently reduce obesity and insulin resistance in both experimental animals and humans. The anti-atherosclerotic effect of acetate is expected owing to its anti-inflammatory and anti-oxidative stress characteristics; however, this remains to be fully understood.

For 12 weeks, apolipoprotein E-deficient mice were administered 0.6 % sodium acetate water or vehicle water. Plaque formation and progression were investigated using histological analysis of dissected aortic root sections. Flow cytometry and gene expression analyses were employed to assess plaque macrophage characteristics and functional states. In vitro tests were performed on mouse peritoneal primary macrophages and bone marrow-derived macrophages isolated from wild-type or GPR43-deficient mice.

Atherosclerotic plaque formation was inhibited in acetate-treated ApoE-deficient mice, and AMPK activation was directly validated in plaque macrophages. Acetate inhibited macrophage proliferation, reactive oxygen species production, and pro-inflammatory molecule expression, all of which were reversed by AMPK inhibition. Bone marrow transplantation study revealed the role of GPR43-mediated AMPK activation by acetic acid in anti-atherosclerotic effect.

Oral acetate administration suppressed arteriosclerosis formation and progression in ApoE-deficient mice. Acetate inhibited macrophage proliferation, inflammatory cytokine release, and reactive oxygen species production via GPR43-mediated AMPK activation in macrophages, ameliorating plaque formation and progression.

Beige adipocytes, crucial for thermogenesis, offer a potential therapeutic strategy for obesity. This study investigated the anti-obesity effects of nonanoic acid (NoA), medium-chain fatty acids, and cholecystokinin-8 (CCK-8) on beige adipogenesis in C3H10T1/2 mesenchymal stem cells (C3H10T1/2 MSCs). We observed a significant increase in cholecystokinin B receptor expression in beige adipocytes compared to preadipocytes. The co-treatment with NoA and CCK-8 enhanced beige adipocyte differentiation and lipid accumulation. Moreover, the co-treatment with NoA and CCK-8 upregulated the mRNA expression of thermogenic genes and increased mitochondrial activity more effectively than individual treatment. Specifically, NoA and CCK-8 co-treatment also elevated the protein expression of uncoupling protein 1 and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. These findings suggest that the additive effect of NoA and CCK-8 promotes the beiging/browning of body fat in beige adipogenesis, potentially serving as an effective approach in the prevention and treatment of obesity and insulin resistance.

The online version contains supplementary material available at 10.1007/s10068-024-01699-6.

Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA). Therefore, we explored the utility of 2-[18F]fluoropropionic acid ([18F]FPA), an SCFA analog, as an imaging biomarker of cardiac injury in mice exposed to doxorubicin.

Cardiotoxicity and cardiac dysfunction were induced in mice by an 8-dose regimen of doxorubicin (cumulative dose 24 mg/kg) administered over 14 days. The effects of doxorubicin exposure were assessed by measurement of heart weights, left ventricular ejection fractions, and blood cardiac troponin levels. Whole body and cardiac [18F]FPA uptakes were determined by PET and tissue gamma counting in the presence or absence of AZD3965, a pharmacological inhibitor of monocarboxylate transporter 1 (MCT1). Radiation absorbed doses were estimated using tissue time-activity concentrations.

Significantly higher cardiac [18F]FPA uptake was observed in doxorubicin-treated animals. This uptake remained constant from 30 to 120 min post-injection. Pharmacological inhibition of MCT1-mediated transport by AZD3965 selectively decreased the uptake of [18F]FPA in tissues other than the heart. Co-administration of [18F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity.

[18F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.

Quantity and source of dietary protein intakes impact the gut microbiota differently. However, these effects have not been systematically studied. This review aimed to investigate these effects whilst controlling for fiber intake. Seven databases were searched, with 50 and 15 randomized controlled trials selected for the systematic review and network meta-analysis respectively. Most gut microbiota-related outcomes showed no significant differences between different protein and fiber intake combinations. Compared to Normal Protein, High Fiber intakes, High Protein, Low Fiber (HPLF) intakes showed greater fecal valerate (SMD = 0.79, 95% CrI: 0.35, 1.24) and plasma trimethylamine N-oxide (TMAO) (SMD = 2.90, 95% CrI: 0.16, 5.65) levels. HPLF intakes also showed greater fecal propionate (SMD = 0.49, 95% CrI: 0.02, 1.07) and valerate (SMD = 0.79, 95% CrI: 0.31, 1.28) levels compared to High Protein, High Fiber intakes. Greater plasma TMAO levels were observed with greater animal protein intakes. Overall, protein quantity and source do not generally alter the gut microbiota composition, although protein quantity can influence microbiota function via modulations in proteolytic fermentation. Both protein and fiber intake should be considered when assessing the impact of dietary protein on the gut microbiota. This trial was registered at PROSPERO (CRD42023391270).

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. Increasing evidence suggests that it is potentially related to gut microbiota, but no prior bibliometric analysis has been performed to explore the most influential works in the relationships between ASD and gut microbiota. In this study, we conducted an in-depth analysis of the most-cited articles in this field, aiming to provide insights to the existing body of research and guide future directions.

A search strategy was constructed and conducted in the Web of Science database to identify the 100 most-cited papers in ASD and gut microbiota. The Biblioshiny package in R was used to analyze and visualize the relevant information, including citation counts, country distributions, authors, journals, and thematic analysis. Correlation and comparison analyses were performed using SPSS software.

The top 100 influential manuscripts were published between 2000 and 2021, with a total citation of 40,662. The average number of citations annually increased over the years and was significantly correlated to the year of publication (r = 0.481, p < 0.01, Spearman's rho test). The United States was involved in the highest number of publications (n = 42). The number of publications in the journal was not significantly related to the journal's latest impact factor (r = 0.016, p > 0.05, Spearman's rho test). Co-occurrence network and thematic analysis identified several important areas, such as microbial metabolites of short-chain fatty acids and overlaps with irritable bowel syndrome.

This bibliometric analysis provides the key information of the most influential studies in the area of ASD and gut microbiota, and suggests the hot topics and future directions. The findings of this study can serve as a valuable reference for researchers and policymakers, guiding the development and implementation of the scientific research strategies in this area.

This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.

Glucose is the main energy source of the brain, yet recent studies demonstrate that fatty acid oxidation (FAO) plays a relevant role in the pathogenesis of central nervous system disorders. We evaluated FAO in brain mitochondria under physiological conditions, in the aging brain, and after stroke. Using high-resolution respirometry we compared medium-chain (MC, octanoylcarnitine) and long-chain (LC, palmitoylcarnitine) acylcarnitines as substrates of β-oxidation in the brain. The protocols developed avoid FAO overestimation by malate-linked anaplerotic activity in brain mitochondria. The capacity of FA oxidative phosphorylation (F-OXPHOS) with palmitoylcarnitine was up to 4 times higher than respiration with octanoylcarnitine. The optimal concentration of palmitoylcarnitine was 10 μM which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20 μM, however, this concentration exceeds MC acylcarnitine concentrations in the brain 15 times. F-OXPHOS capacity was highest in mouse cerebellum, intermediate in cortex, prefrontal cortex, and hypothalamus, and hardly detectable in hippocampus. F-OXPHOS capacity was 2-fold lower and concentrations of LC acylcarnitines were 2-fold higher in brain of aged rats. A similar trend was observed in the rat model of endothelin-1-induced stroke, but reduction of OXPHOS capacity was not limited to FAO. In conclusion, although FAO is not a dominant pathway in brain bioenergetics, it deserves specific attention in studies of brain metabolism.

Aneurysmal subarachnoid hemorrhage (aSAH) results in a complex systemic response that is critical to the pathophysiology of late complications and has important effects on outcomes. Omics techniques have expanded our investigational scope and depth into this phenomenon. In particular, metabolomics-the study of small molecules, such as blood products, carbohydrates, amino acids, and lipids-can provide a snapshot of dynamic subcellular processes and thus broaden our understanding of molecular-level pathologic changes that lead to the systemic response after aSAH. Lipids are especially important due to their abundance in the circulating blood and numerous physiological roles. They are comprised of a wide variety of subspecies and are critical for cellular energy metabolism, the integrity of the blood-brain barrier, the formation of cell membranes, and intercellular signaling including neuroinflammation and ferroptosis. In this review, metabolomic and lipidomic pathways associated with aSAH are summarized, centering on key metabolites from each metabolomic domain.

Infants with biliary atresia experience gastrointestinal malabsorption of long-chain triglycerides and are commonly supplemented with medium-chain triglyceride (MCTs) that can be passively absorbed. The aim was to investigate the association of MCT supplementation with growth, nutritional status and clinical outcomes in infants with biliary atresia.

Infants who underwent Kasai portoenterostomy and were followed up for at least two years or until death or transplantation were reviewed. Infants with comorbidities affecting growth or outcome were excluded. Data were extracted from medical records from more than a decade in relation to MCT supplementation, growth, nutritional status and clinical outcome at baseline, 6-weeks, 3-, 6-, 12- and 24-months. Mixed-effects modelling was used to test associations of MCT in the first six months with these outcomes.

Of 200 infants (108 male), 108 (54 %) were alive with native liver at two years, 84 (42 %) underwent liver transplantation and eight (4 %) died. MCT percentage prescribed was mean 57.3 % (SD 11.2) while MCT intake was median 2.7 (IQR 2.2, 3.8) g/kg/d. For every g/kg/d MCT consumed, the rate of change in z-score for weight was -0.27 (95 % CI -0.37 to -0.17) and length was -0.31 (-0.42 to -0.17) (both p < 0.001). Compared to the low MCT group (<2.7 g/kg/d), the high group (≥2.7 g/kg/d) consumed more energy (118 vs. 108 kcal/kg; p < 0.001), however, at 3-months they had lower weight (-1.7 (1.2) v. -1.0 (1.2) and length (-1.3 (1.1) v. -0.6 (1.4) z-scores (both p < 0.001) but no differences in growth at later time points. There was no overall association between MCT and nutritional status or clinical outcomes.

This is the first study to investigate the association of MCT with growth, nutritional status and clinical outcomes in biliary atresia. No association was found between MCT with growth beyond 3-months, overall nutritional status or clinical outcomes. The association between MCT (g/kg/d) and poorer growth in the first 3-months may be explained by infants with poorer growth drinking more or being prescribed more MCT formula milk. A randomised controlled trial could help to better understand this association.

Weaning in piglets presents significant physiological and immunological challenges, including gut dysbiosis and increased susceptibility to post-weaning diarrhoea (PWD). Abrupt dietary, environmental, and social changes during this period disrupt the intestinal barrier and microbiota, often necessitating antimicrobial use. Sustainable dietary strategies are critical to addressing these issues while reducing reliance on antimicrobials. Reducing dietary crude protein mitigates the availability of undigested proteins for pathogenic bacteria, lowering harmful by-products like ammonia and branched-chain fatty acids, which exacerbate dysbiosis. Organic acid supplementation improves gastric acidification, nutrient absorption, and microbial balance, while also serving as an energy-efficient alternative to traditional grain preservation methods. Increasing intestinal butyrate, a key short-chain fatty acid with anti-inflammatory and gut-protective properties, is particularly promising. Butyrate strengthens intestinal barrier integrity by upregulating tight junction proteins, reduces inflammation by modulating cytokine responses, and promotes anaerobic microbial stability. Exogenous butyrate supplementation via salts provides immediate benefits, while endogenous stimulation through prebiotics (e.g., resistant starch) and probiotics promotes sustained butyrate production. These interventions selectively enhance butyrate-producing bacteria such as Roseburia and Faecalibacterium prausnitzii, further stabilising the gut microbiota. Integrating these strategies can enhance gut integrity, microbial resilience, and immune responses in weaned piglets. Their combination offers a sustainable, antimicrobial-free approach to improving health and productivity in modern pig production systems.

The present study investigates the impact of supplementing diets with a synergistic blend of short- and medium-chain fatty acids (SCFAs-MCFAs) during the peripartum and lactation phases on early microbial colonization and the subsequent growth performance of newborn pigs. The experiment involved 72 sows and their litters, with a follow-up on 528 weaned pigs. Sows were fed either a control diet or a diet supplemented with SCFAs-MCFAs and the pigs were monitored for their growth performance and microbial populations. Subsequently, selected weaned pigs were allotted to an SCFAs-MCFAs diet according to the maternal diet. Results showed that SCFAs-MCFAs supplementation led to reduced backfat loss in sows and improved pig weight and uniformity at weaning (p < 0.05). Additionally, suckling pigs exhibited significant shifts in gut microbiota, including increased lactic acid bacteria and reduced Streptococcus suis populations (p < 0.05). Although there was no influence of maternal diet on pig growth after weaning, there was a modulation on bacterial populations at 7 and 35 days post-weaning. Pigs fed SCFAs-MCFAs demonstrated improved feed efficiency with notable reductions in E. coli and Streptococcus suis counts. The findings suggest that maternal dietary supplementation with SCFAs-MCFAs can positively influence both sow and pig performance, offering a potential strategy to enhance productivity and health in the commercial swine production.

Short-chain fatty acids (SCFAs), primarily derived from gut microbiota, play a role in regulating fetal development; however, the mechanism remains unclear. Fetal SCFAs levels depends on maternal SCFAs transported via the placenta. Metabolic stress, particularly from diabetes and obesity, can disrupt maternal SCFAs levels, impairing fetal metabolic reprogramming. Dysregulated SCFAs may negatively impact the development of the fetal cardiovascular, nervous, and immune systems, potentially contributing to adverse outcomes in adulthood. This review focuses on recent advances regarding the role of maternal SCFAs in shaping the metabolic profile of offspring, especially in the context of various maternal metabolic disorders. Given that SCFAs may influence fetal development through the placenta-embryo axis, targeted SCFAs supplementation could be a promising strategy against developmental diseases associated with intrauterine risk factors.

Postprandial lipemia (PPL) has been recognised as a cardiovascular disease risk factor. Appetite and PPL can be influenced by the length of saturated fatty acids (FAs). Thus, this study aims to investigate if different FA chain lengths have different impacts on appetite and PPL in healthy volunteers.

This is a randomised crossover single-blinded intervention study of 20 healthy adults. Coconut oil and palm oil were consumed in the form of biscuits. Blood serum samples were withdrawn after an overnight fast and 1, 2, 4 and 6 hours after eating the test meals and examined for blood lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and triglycerides (TG)), while Friedewald's equation was used to calculate low-density lipoprotein (LDL). Visual analogue scales were used by participants to rate their appetites, and an ad libitum meal was weighed to determine the energy intake.

The net area under the curve of TG and TC following the coconut oil were significantly lower than following the palm oil (P value ≤0.05). In the mean of the change in TC, LDL and HDL from the baseline, a significant difference was found after 6 hours of eating the biscuits (P value ≤0.05). The perceptions of hunger and fullness did not significantly differ between the two types of FAs. Also, the energy and macronutrient intakes were not significantly different after the two types of oil, neither at the ad libitum meal nor on the day following the treatments.

The selection of FA chain length may influence PPL, and thus cardiovascular disease risk in a way that is functionally significant. However, this study detected no influence of FA chain length on appetite up to 40 hours post-treatment.

NCT05539742.

This study investigated the effects of xylo-oligosaccharide supplementation on the production performance, intestinal morphology, cecal short-chain fatty acid levels, and gut microbiota of laying hens. A total of 800 Lohmann pink layers, each 48 wk old, were randomly divided into 5 dietary treatment groups, namely XOS at 0 (CON), 100 (XOS1), 200 (XOS2), 300 (XOS3) and 400 (X0S4) mg/kg. The experimental period was 24 wk. The results revealed that the egg production rate and the number of eggs laid by each layer between 1 to 12 wk increased as the XOS concentration increased (Plinear < 0.05). The sand-shell egg percentage decreased significantly from 1 to 12 wk in the XOS1, XOS2, and XOS3 groups (PANOVA < 0.05). Compared with the CON group, the 4 XOS dosage groups presented significant increases in the villus height and the ratio of villus height to crypt depth in the jejunum (PANOVA < 0.05), whereas a linear decrease in jejunal crypt depth (Plinear < 0.05) was noted. In addition, XOS supplementation significantly increased the concentrations of butyric acid and isovaleric acid in the caeca (PANOVA < 0.05). High-throughput sequencing analysis of bacterial 16S rRNA revealed that dietary XOS supplementation influenced the cecal microbiota. The alpha diversity analysis indicated that the richness of cecal bacteria was greater in the laying hens fed XOS. The modulation of the cecal microbiota composition upon the addition of XOS was characterized by an increased abundance of Firmicutes and Bifidobacteriaceae, and decreased abundance of Bacteroidetes. At the genus level, dietary XOS supplementation resulted in decreases in the abundances of Bacteroides and Rikenellaceae_RC9_gut_group and an increase in the abundance of Lactobacillus. In conclusion, dietary XOS supplementation improved the production performance of laying hens by increasing the production of short-chain fatty acids and improving their intestinal morphology, which was achieved mainly through changes in the composition of the intestinal microbiota. The recommended level of XOS in the diet of laying hens is 200 mg/kg.

In recent decades, several discoveries have been made that force us to reconsider old ideas about mitochondria and energy metabolism in the light of these discoveries. In this review, we discuss metabolic interaction between various organs, the metabolic significance of the primary substrates and their metabolic pathways, namely aerobic glycolysis, lactate shuttling, and fatty acids β-oxidation. We rely on the new ideas about the supramolecular structure of the mitochondrial respiratory chain (respirasome), the necessity of supporting substrates for fatty acids β-oxidation, and the reverse electron transfer via succinate dehydrogenase during β-oxidation. We conclude that ATP production during fatty acid β-oxidation has its upper limits and thus cannot support high energy demands alone. Meanwhile, β-oxidation creates conditions that significantly accelerate the cycle: glucose-aerobic glycolysis-lactate-gluconeogenesis-glucose. Therefore, glycolytic ATP production becomes an important energy source in high energy demand. In addition, lactate serves as a mitochondrial substrate after converting to pyruvate + H+ by the mitochondrial lactate dehydrogenase. All coupled metabolic pathways are irreversible, and the enzymes are organized into multienzyme structures.

The interaction between the gut-microbiota-derived metabolites and brain has long been recognized in both health and disease. The liver, as the primary metabolic organ for nutrients in animals or humans, plays an indispensable role in signal transduction. Therefore, in recent years, Researcher have proposed the Gut-Liver-Brain Axis (GLBA) as a supplement to the Gut-Brain Axis. The GLBA plays a crucial role in numerous physiological and pathological mechanisms through a complex interplay of signaling pathways. However, gaps remain in our knowledge regarding the developmental and functional influences of the GLBA communication pathway. The gut microbial metabolites serve as communication agents between these three distant organs, functioning prominently within the GLBA. In this review, we provide a comprehensive overview of the current understanding of the GLBA, focusing on signaling molecules role in animal and human health and disease. In this review paper elucidate its mechanisms of communication, explore its implications for immune, and energy metabolism in animal and human, and highlight future research directions. Understanding the intricate communication pathways of the GLBA holds promise for creating innovative treatment approaches for a wide range of immune and metabolic conditions.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.