Tissue Metabolism Research Articles

Monitoring of perioperative tissue perfusion and impact on patient outcomes

Monitoring perioperative tissue perfusion is crucial in clinical anesthesia to protect organs and ensure patient safety. Indicators like hemodynamic parameters, tissue metabolism, and microcirculation markers are used for assessment. Studies show intraoperative hypotension negatively impacts outcomes, though blood pressure alone may not reflect tissue perfusion accurately. Cardiac output is a more direct measure, with adequate levels generally indicating good perfusion. However, some conditions cause adequate cardiac output but inadequate perfusion. Non-quantitative markers like skin color and temperature, and quantitative indicators like tissue oxygen saturation and laser Doppler flowmetry, help assess microcirculation but can’t fully evaluate systemic perfusion. Near-Infrared Spectroscopy (NIRS) monitors tissue oxygen metabolism, reflecting oxygen supply and consumption balance. Central venous oxygen saturation offers a better systemic overview but may not always indicate good perfusion, especially in sepsis. Lactic acid levels closely correlate with tissue perfusion and outcomes, with dynamic changes being more indicative than single measurements. Effective monitoring requires evaluating both macro- and microcirculation states and systemic metabolic levels to ensure optimal outcomes. Combining these measures provides a more accurate assessment of tissue perfusion and patient prognosis.

Metabolomic analysis of murine tissues infected with Brucella melitensis.

Brucella is a gram negative, facultative intracellular bacterial pathogen that constitutes a substantial threat to human and animal health. Brucella can replicate in a variety of tissues and can induce immune responses that alter host metabolite availability. Here, mice were infected with B. melitensis and murine spleens, livers, and female reproductive tracts were analyzed by GC-MS to determine tissue-specific metabolic changes at one-, two- and four- weeks post infection. The most remarkable changes were observed at two-weeks post-infection when relative to uninfected tissues, 42 of 329 detected metabolites in reproductive tracts were significantly altered by Brucella infection, while in spleens and livers, 68/205 and 139/330 metabolites were significantly changed, respectively. Several of the altered metabolites in host tissues were linked to the GABA shunt and glutaminolysis. Treatment of macrophages with GABA did not alter control of B. melitensis infection, and deletion of the putative GABA transporter BMEI0265 did not alter B. melitensis virulence. While glutaminolysis inhibition did not affect control of B. melitensis in macrophages, glutaminolysis was required for macrophage IL-1β production in response to B. melitensis. In summary, these results indicate that Brucella infection alters host tissue metabolism and that these changes could have effects on inflammation and the outcome of infection.

Therapeutic effects of traditional Chinese medicine Hua-Feng-Dan in a rat model of ischemic stroke involve renormalization of gut microbiota

Hua-Feng-Dan is a traditional Chinese medicine used to treat ischemic stroke, but little is known about its therapeutic mechanism. This study explored whether and how the mechanism involves readjustment of gut microbiota. Rats were subjected to middle cerebral artery occlusion as a model of ischemic stroke or to sham surgery, then treated or not with Hua-Feng-Dan. The different groups of animals were compared in terms of neurological score, cerebral infarct volume, brain edema, brain and gut histopathology to assess stroke severity. They were also compared in terms of indices of intestinal barrier permeability, inflammation and oxidative stress, brain metabolites as well as composition of the gut microbiota and their metabolites. Hua-Feng-Dan significantly reduced cerebral infarct volume and brain water content and improved neurological score, ischemic brain histopathology, and gut histopathology. It partially reversed stroke-induced intestinal barrier disruption and leakage, inflammation, dyslipidemia and oxidative stress, as well as the stroke-induced increase in pathogenic gut microbiota (e.g., Escherichia-Shigella, Enterococcus, Clostridium_innocuum_group) and decrease in beneficial microbiota (e.g., Lachnospiraceae, unclassified__f__Lachnospiracea and Ruminococcus_torques_group). The treatment altered levels of 39 and 38 metabolites produced during gut microbial and brain tissue metabolism respectively, mainly of amino acids, nucleosides, short-chain fatty acids, and essential fatty acids. Levels of factors related to inflammation and intestinal barrier permeability correlated positively with relative abundance of Escherichia-Shigella and Clostridium_innocuum_group, and negatively with 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, dihomo-α-linolenic acid, dihomolinoleic acid, and 10-nitrolinoleic acid. Conversely, levels of 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, and 10-nitrolinoleic acid correlated positively with relative abundance of unclassified__f__Lachnospiracea. Our results suggest that Hua-Feng-Dan may mitigate ischemic stroke injury by renormalizing gut microbiota and restoring gut barrier function, gut metabolism, thereby helping to alleviate inflammatory, neurological damage, and brain metabolic disorders.

Artificial light at night effects glucose metabolism in the developing jawbone by inhibiting melatonin secretion

Objective: To investigate the effects of artificial light at night on the growth of mandibles in mice and its regulatory mechanisms. Methods: A mouse model of artificial light at night (night light pollution group) and normal lighting (normal light group) was established by controlling light exposure time, with 4 mice in each group. Micro-CT was employed to analyze the differences in bone quantities of the mandibles between the two groups. Real-time fluorescence quantitative PCR (RT-qPCR) was used to examine the expression levels of osteogenic differentiation and metabolism-related genes in the cortical bone and condylar ossification center of the mandibles. Enzyme-linked immunosorbent assay was utilized to assess the diurnal variation of serum melatonin concentrations between the two groups. The artificial light at night experimental group received daily timed injections of a defined dose of melatonin to restore the diurnal variation of serum melatonin concentration in the mice, while the normal light group and the artificial light at night control group received the same volume of saline. Bone quantities, mandibular tissue morphologies, ossification differentiation in the condylar region and cortical bone, as well as glucose metabolism expression differences were assessed across the three groups. Results: The cortical bone thickness of the mandibles in the artificial light at night group [(0.196±0.017) mm] was significantly less than that in the control group [ (0.228±0.007) mm] (P=0.029). The bone volume fraction of the condylar ossification center in the artificial light at night group [(36.90±1.09) %] was significantly lower than that in the normal light group [(54.24±1.49) %] (P<0.001). The length of the mandible in the artificial light at night group [(10.86±0.17) mm] was significantly shorter than that in the normal light group [(11.41±0.32) mm] (P=0.032). RT-qPCR results indicated that the expressions of osteogenic-related genes alkaline phosphatase, liver/bone/kidney (Alpl), osteocalcin (Ocn), Runt-related transcription factor 2 (Runx2), and osterix (Osx) in the cortical bone and condylar ossification center of mice in the artificial light at night group were significantly lower than those in the normal light group (all P<0.05). The expression of metabolism-related genes protein kinase, AMP activated alpha 1 (Prkaa1), V-type proton ATPase subunit d 1 (Atp6v0d1), and cytochrome C oxidase subunit Ⅳ isoform 1 (Cox4i1) in the cortical bone and condylar ossification center of mice in the artificial light at night group were also significantly reduced compared to normal mice (all P<0.01). The serum melatonin concentration peaked 8 hours after lights off in the normal light group, whereas the artificial light at night group exhibited a significantly reduced nocturnal serum melatonin concentration with no apparent peak compared to the normal light group. Micro-CT results demonstrated that after artificial light at night group mice received timed melatonin supplementation daily, the thickness of cortical bone, the bone volume fraction of the condylar ossification center, and the length of the mandible were all significantly higher than those in the artificial light at night group (all P<0.05). Histological staining results indicated that the cortical bone structure of the mandibles in the melatonin supplementation group was more organized than that of the artificial light at night group, with higher brain and muscle ARNT-like 1 (BMAL1) expression (P=0.003). RT-qPCR results further showed that the expression levels of Prkaa1, Atp6v0d1, and Cox4i1 in the cortical bone and condylar ossification center significantly increased in the melatonin supplementation group compared to the artificial light at night group (all P<0.05), but still significantly lower than those in the normal light group (all P<0.05). Additionally, the RT-qPCR results further revealed that the expression levels of osteogenic differentiation-related genes Alpl, Ocn, and Runx2 in the cortical bone and condylar ossification center of the melatonin supplementation group were significantly higher than those in the artificial light at night group (all P<0.01). Western blotting analysis indicated that the expression levels of glucose metabolism and osteogenic-related proteins RUNX2, OSX, ATP6V0D1, and COX Ⅳ, along with the phosphorylation levels of AMPKα1/α2, were significantly higher in the melatonin supplementation group compared to the artificial light at night group (all P<0.01). Conclusions: Artificial light at night can inhibit melatonin secretion in mice, reduce glucose metabolism in mandibular tissues, and affect both intramembranous and chondrogenic ossification activities, ultimately leading to inadequate mandibular development.

Effects of Salmonella Typhimurium infection on intestinal flora and intestinal tissue arachidonic acid metabolism in Wenchang chickens

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether arachidonic acid (ARA) metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and ARA metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), lipoxin A4 (LXA4), ± 8(9)-EET, ± 11(12)-EET, and ± 8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (Phospholipase A2 PLA2 and Cyclooxygenase-2 COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including Interferon-γ (IFN-γ), Transforming growth factor-β1 (TGF-β1), Interleukin-4 (IL-4), and Interleukin-6 (IL-6). In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. The present study revealed the structure of cecal flora in S. Typhimurium-infected Wenchang chickens. In addition, this study demonstrated that S. Typhimurium activates the ARA cyclooxygenase metabolic pathway, which in turn mediates the development of intestinal inflammation in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease.

Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.

Circadian metabolic adaptations to infections.

Circadian clocks are biological oscillators that evolved to coordinate rhythms in behaviour and physiology around the 24-hour day. In mammalian tissues, circadian rhythms and metabolism are highly intertwined. The clock machinery controls rhythmic levels of circulating hormones and metabolites, as well as rate-limiting enzymes catalysing biosynthesis or degradation of macromolecules in metabolic tissues, such control being exerted both at the transcriptional and post-transcriptional level. During infections, major metabolic adaptation occurs in mammalian hosts, at the level of both the single immune cell and the whole organism. Under these circumstances, the rhythmic metabolic needs of the host intersect with those of two other players: the pathogen and the microbiota. These three components cooperate or compete to meet their own metabolic demands across the 24 hours. Here, we review findings describing the circadian regulation of the host response to infection, the circadian metabolic adaptations occurring during host-microbiota-pathogen interactions and how such regulation can influence the immune response of the host and, ultimately, its own survival.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.

Transcriptomics reveals the regulatory mechanisms of circRNA in the muscle tissue of cows with ketosis postpartum.

The transition period from late pregnancy to early lactation in dairy cows involves significant metabolic changes to cope with the challenges related to energy metabolism. Muscle tissue, as the largest energy-metabolizing tissue in dairy cows, plays a crucial role in energy metabolism. Furthermore, circular RNAs (circRNAs) have been shown to play key roles in various biological events. However, the regulatory mechanisms of energy metabolism and muscle cells mediated by circRNAs in the muscle tissue of ketotic dairy cows remain unclear. Here, we identified a total of 5103 circRNAs in the muscle tissue of ketosis-affected cows. Among these, compared to healthy cows, 57 circRNAs were differentially expressed in the muscle tissue of ketosis-affected cows, with 39 upregulated and 18 downregulated. Functional enrichment analysis based on the source genes of circRNAs indicated that circ-30,628 is closely related to carbon metabolism, and circ-CoQ2 is associated with mitochondrial energy metabolism. Given the sponge effect of circRNAs on miRNAs, we further predicted the network relationships of downstream miRNAs and mRNAs of circ-30,628 and circ-CoQ2, and found that their downstream target genes are involved in signaling pathways such as MAPK, Wnt, FoxO, and autophagy, which is associated with the proliferation, differentiation, energy metabolism, oxidative stress, and mitochondrial function of muscle cells. In summary, these findings provide a theoretical basis for understanding the functions of circRNAs regulating energy metabolism in the muscle tissue of ketosis-affected cows, thereby reducing the accumulation of ketone bodies to prevent the occurrence of ketosis in dairy cows.

Blood circulating LncRNAs: SNHG5 and ZFAS1 as biomarkers reflecting cachexia incidence in chronic heart failure patients.

Systemic inflammation plays a crucial role in the development and progression of chronic heart failure (CHF) across all phenotypes. The continuous release of pro-inflammatory cytokines causes muscle atrophy and adipocyte breakdown, ultimately resulting in cachexia. Long non-coding RNAs (lncRNAs) are emerging as potential biomarkers associated with cachexia, as they indirectly regulate muscle and fat tissue metabolism. This study aimed to identify inflammatory-related, plasma-circulating lncRNAs characteristic of cachexia in CHF patients. The secondary objective was to assess the clinical utility of these selected lncRNAs as diagnostic and predictive markers for cachexia. Blood plasma samples were collected from 157 newly diagnosed CHF patients (91 men and 66 women; mean age: 72±13 years) for lncRNA extraction. Molecular testing, using RT2 lncRNA qRT-PCR Array Human Cell Development, Differentiation, and Inflammatory Panel was performed in two phases: the discovery phase (screening of 148 lncRNAs in 8 patients) and the validation phase (validation of the identified lncRNAs in 157 patients). Five lncRNAs were found as differentially expressed in the discovery phase. In the validation phase, two of these five lncRNAs: SNHG5 and ZFAS1, showed significant expression differences between cachectic and non-cachectic patients in the entire study group (both p<0.001). The combined downregulation of ZFAS1 and upregulation of SNHG5 was identified as an unfavorable lncRNA signature primarily associated with poor nutritional status in women (low fat-free mass, fat-free mass index and body mass index), abnormal laboratory results (hypoalbuminemia and high levels of inflammatory markers), and an increased incidence of cachexia in CHF patients. When this lncRNA signature was combined with serum CRP and albumin levels, it effectively differentiated between cachectic and non-cachectic patients (AUC=1.0). The presence of this unfavorable signature was associated with a 9-fold increased likelihood (OR=9.2) of cachexia in the study cohort. The identified lncRNA signature demonstrates potential clinical value for distinguishing and predicting cachexia in CHF patients.

Effect of hydro-ethanol extract of Caesalpinia pulcherrima (L.) Sw. leaves in human and rat: In vitro approach of male contraceptive development.

The study focused the contraceptive efficacy of hydro-ethanolic (60:40) extract (HEE) of Caesalpinia pulcherrima leaves in human and rat sperm samples by in vitro study. Six young fertile adult males were selected for semen collection. Sperm samples were collected from six adult rat also by chopping the epididymis along with the collection of testicles, epididymis, and liver. The semen, sperm, and tissue samples were grouped into control, 1, 2, and 4 mg HEE exposed categories. Sensitive spermiological sensors, androgenic key enzymes, oxidative stress, and metabolic toxicity markers were assessed according to standard protocols. Human semen samples, rat sperm samples and metabolic tissue samples were divided into 16 test tubes in all of the above groups to find out the direct effect of the extract on such sensors in concentration and duration dependent manner. Spermiological sensors both in human and rat were decreased significantly (p<0.05) in concentration and duration dependent manner after in vitro exposure of HEE against the control group. Testicular ∆5,3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, superoxide dismutase, and catalase activities were significantly (p<0.05) decreased, and level of the end product of lipid oxidation-peroxidation was elevated (p<0.05) in rat after extract charging. No general toxicity imposition of the said extract indicated by the activities of hepatic transaminases. Phytochemical screening was done by qualitative and liquid chromatography-mass spectrometry analysis. Extract focused the promising male contraceptive potentiality at 2 mg/ml concentration. Mode of action will be unfolded from running in vivo study very shortly.

Preparation of Morchella esculenta protein and its preventive effect on nonalcoholic fatty liver disease in mice.

Morchella esculenta is a valuable edible fungus with multidimensional bioactivities; however, research on M. esculenta protein and its beneficial effects on nonalcoholic fatty liver disease (NAFLD) have been limited. In this study, M. esculenta protein (MEP) with 80.59% protein content was prepared, isolated, and characterized by the complete amino acid composition. The main molecular weight of the protein ranged from 65 to 120 kDa, with 100 kDa being the most dominant band, and it exhibited an alpha helix structure when analyzed by FT-IR and circular dichroism analysis. MEP could regulate body weight, fat accumulation, and alleviate lipid metabolism in adipose tissues in mice with high-fat diet-induced NAFLD. MEP prevented hepatic lipotoxicity, which was reflected in attenuating liver steatosis in vitro and in vivo, thereby regulating the levels of related factors involved in lipid metabolism (e.g., PPARs, HNF-4, SREBP, FASN, ACC-1, and CD36). Furthermore, it inhibited oxidative stress response, which can be attributed to the activation of the MAPK/PGC-1α pathway. Additionally, MEP exhibited probiotic effects, as demonstrated by the altered gut microbiota composition and improved the intestinal barrier integrity. Thus, this study confirmed the preventive effect of MEP against NAFLD by regulating the gut-liver cross-talk, which provided a theoretical basis for the development and utilization of M. esculenta.

Mechanisms of Lipid-Associated Macrophage Accrual in Metabolically Stressed Adipose Tissue.

Adipose tissue (AT) inflammation, a hallmark of the metabolic syndrome, is triggered by overburdened adipocytes sending out immune cell recruitment signals during obesity development. An AT immune landscape persistent throughout weight loss and regain constitutes an immune-obesogenic memory that hinders long-term weight loss management. Lipid-associated macrophages (LAMs) are emerging as major players in diseased, inflamed metabolic tissues and may be key contributors to an obesogenic memory in AT. Our previous study found that LAM abundance increases with weight loss via intermittent fasting (IF) in obese mice, which is driven by adipocyte p53 signalling. However, the specific signals causing LAM accumulation in AT under IF remain unknown. In this piece, we hypothesise on a range of adipocyte-secreted signals that can harbor immune-attractive features upon fasting/refeeding cycles. We highlight possible mechanisms including cell death signalling, matrikines, and other damage-associated molecular patterns (DAMPs), as well as adipo(-cyto)kines, lipid mediators, metabolites, extracellular vesicles, and epigenetic rewiring. Finally, we consider how advances in mechanisms of AT LAM recruitment gleaned from preclinical models might be translatable to long-term weight management in humans. Thus, we provide vantage points to study signals driving monocyte recruitment, polarisation towards LAMs, and LAM retention, to harness the therapeutic potential of modulating AT LAM levels by impacting the immune-obesogenic memory in metabolic disease.

Endothelial autophagy-related gene 7 contributes to high fat diet-induced obesity.

Obesity-associated metabolic dysfunction is a major public health concern worldwide. Endothelial dysfunction is a hallmark of metabolic dysfunction, and endothelial cells affect metabolic functions. Because autophagy-related gene 7 (ATG7) is involved in various cellular physiology, we investigated the roles of endothelial cell-ATG7 (EC-ATG7) on high-fat diet-induced obesity and its related metabolic dysfunction. We generated an endothelial-specific Atg7 knock-out mouse by breeding Atg7flox/flox mouse with the Chd5-Cre mouse, and investigated the metabolic phenotypes associated with high-fat diet (HFD)-induced obesity. Body weight, food intake, glucose tolerance, insulin sensitivity, and liver fat accumulation were measured in endothelial Atg7 deficient (Atg7ΔEnd) and control mice (Atg7f/f). Adipose tissue inflammation was assessed by measuring the expression of pro-inflammatory genes. Furthermore, we performed indirect calorimetry and examined the insulin signaling pathway molecules. We found that deletion of EC-Atg7 ameliorated HFD-induced weight gain, fatty liver, and adipocyte hypertrophy and inflammatory response in adipose tissue, and improved insulin sensitivity without changing glucose tolerance. These metabolic effects seem to be due to the reduced food intake because there were no differences in energy expenditure, energy excretion to feces, and physical activity. Interestingly, the deletion of EC-Atg7 protected from HFD-induced vascular rarefaction, and the knock-down of Atg7 in endothelial cells protected from fatty acid-induced cell death. Our results suggest that EC-Atg7 deletion ameliorates HFD-induced obesity and its related metabolic dysfunction, such as insulin resistance and fatty liver by attenuating appetite and vascular rarefaction. The EC-Atg7 deletion may protect the endothelial cells from lipotoxicity and impaired angiogenesis, which preserves the endothelial function in metabolic tissues. These findings may have implications for developing new therapeutic strategies for preventing and treating obesity and its associated health risks.

Role of transforming growth factor-β1 in regulating adipocyte progenitors

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206+ M2-like macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism, remains unknown. We used CD206CreERT2; Tgf-β1f/f mouse model in which the Tgf-β1 gene was conditionally deleted in CD206+ M2-like macrophages followed by tamoxifen administration, to investigate the role of the Tgf-β1 gene in glucose and insulin metabolism. Our data demonstrated that lack of CD206+ M2-like macrophages derived Tgf-β1 gene improved glucose metabolism and insulin sensitivity by enhancing adipogenesis via hyperplasia. The Tgf-β1 gene, specifically from CD206+ M2-like macrophages, deletion stimulated APs’ proliferation and differentiation, leading to the generation of smaller mature adipocytes, therefore enhancing insulin sensitivity and improving glucose metabolism under normal chow conditions. Our study brings a new perspective that Tgf-β1 gene deletion specific from CD206+ M2-like macrophage promotes adipocyte hyperplasia, improving glucose homeostasis and insulin sensitivity in the lean state.

The Counteracting Effect of Chrysin on Dietary Fructose-Induced Metabolic-Associated Fatty Liver Disease (MAFLD) in Rats with a Focus on Glucose and Lipid Metabolism.

The prevalence of metabolic syndrome has been exponentially increasing in recent decades. Thus, there is an increasing need for affordable and natural interventions for this disorder. We explored the effect of chrysin, a dietary polyphenol, on hepatic lipid and glycogen accumulation, metabolic dysfunction-associated fatty liver disease (MAFLD) activity score and oxidative stress and on hepatic and adipose tissue metabolism in rats presenting metabolic syndrome-associated conditions. Rats fed a chow diet were separated into four groups: Control (tap water), Fructose (tap water with 10% fructose), Chrysin (tap water+ chrysin (100 mg/kg body weight/d)), and Fructose + Chrysin (tap water with 10% fructose + chrysin (100 mg/kg body weight/d, daily)) (for 18 weeks). When associated with the chow diet, chrysin reduced hepatic lipid and glycogen storage, increased the hepatic antioxidant potential of glutathione and reduced de novo lipogenesis in the adipose tissue. When associated with the high fructose-diet, chrysin attenuated the increase in lipid and glycogen hepatic storage, improved the MAFLD activity score, decreased hepatic lipid peroxidation, increased the antioxidant potential of glutathione, and improved lipid and glucose metabolic markers in the liver and adipose tissue. In conclusion, our results suggest that chrysin is a beneficial addition to a daily diet for improvement of hepatic metabolic health, particularly for individuals suffering from metabolic syndrome.

Mouse models for metabolic health research: molecular mechanism of exercise effects on health improvement through adipose tissue remodelling.

Exercise provides health benefits to multiple metabolic tissues through complex biological pathways and interactions between organs. However, investigating these complex mechanisms in humans is still limited, making mouse models extremely useful for exploring exercise-induced changes in whole-body metabolism and health. In this review, we focus on gaining a broader understanding of the metabolic phenotypes and molecular mechanisms induced by exercise in mouse models. We first discuss the differences in adaptations induced by aerobic and resistance exercise, and compare voluntary wheel running and forced treadmill exercise, the two main methods of aerobic exercise research in mice, to show the similarities and differences between the same aerobic exercise but different methods, and their impact on experimental outcomes. The effects of exercise on metabolic phenotypes, including alleviation of obesity and metabolic disorders, and the mechanisms involved in adipose tissue remodelling and browning are explored, as well as the role of the gut microbiota in mediating the physiological responses and metabolic effects of exercise. Understanding these molecular mechanisms and methodological aspects of exercise experiments in mouse models can serve as a valuable template for the design of future basic research in exercise physiology and will provide a strong scientific evidence base for optimizing the design of exercise intervention programmes for metabolic health.

Dual Ratiometric Fluorescence Sensors Based on Chiral Carbon Dots for the Sensitive and Specific Detection of Arginine.

Arginine (Arg) is involved in tissue metabolism and regulates the immune function; thereby, achieving the detection of Arg is crucial for early diagnosis and treatment of diseases. Herein, dual ratiometric fluorescence sensors were prepared with the blue emission of levorotatory/dextrorotatory carbon dots (CDs) and the red emission of porphyrin (L/D-CDs-PP) for the sensitive and portable detection of Arg. Interestingly, L-CDs-PP and D-CDs-PP displayed not only the dual emission peaks at 493 and 650 nm but also different response modes to Arg; thus, they could serve as dual ratiometric fluorescence sensors to achieve the accurate and reliable detection of Arg, with the detection limit of 23.87 μM for L-CDs-PP and 2.39 μM for D-CDs-PP. Importantly, the solid-state sensors successfully achieved dual-mode visual and portable detection of Arg with the support of a smartphone platform. In addition, L-CDs-PP and D-CDs-PP exhibited excellent biocompatibility and cell imaging capabilities, and they could achieve the detection of Arg in cells and biological samples of urine and rat plasma. Therefore, the dual ratiometric fluorescence sensors exhibited broad application prospects in the fields of analytical sensing, biological imaging, and medical diagnosis.

Undernutrition affects metabolism and immune response in subcutaneous adipose tissue of pregnant ewes.

Pregnant ewes mobilize body fat to increase energy supply for fetal growth and development upon undernutrition, which disrupts the metabolic homeostasis of the body. However, the comprehensive metabolic changes in subcutaneous adipose tissue upon undernutrition are poorly understood. In this study, an undernutrition sheep model was established to investigate the effects of undernutrition on metabolic changes, immune response, and inflammation in subcutaneous fat through transcriptome, RT-qPCR, and metabolome analysis. Results showed that undernutrition changed the total transcriptional and metabolic profiles of adipose tissue. Compared to the controls, differentially expressed genes (DEGs) involved in fatty acid synthesis, triglyceride genesis, and lipid transport were downregulated in undernourished ewes, while DEGs related to fatty acid and triglyceride degradation were upregulated. Almost all lipid-related differential metabolites (DMs) were downregulated. DEGs and DMs involved in glucose metabolism and glycogen degradation were downregulated, while glycogen synthesis and carbohydrate transport were upregulated. DEGs linked to amino acid degradation were upregulated and some amino acids and derivatives were downregulated. KEGG pathway analysis showed complement and coagulation cascades were enriched significantly by DEGs, and DEGs related to coagulation, macrophage, and inflammation were upregulated while DEGs associated with the complement system were downregulated. Undernutrition during late gestation disrupted the metabolism of lipids, carbohydrates, and amino acids in adipose tissue, which weakened the complement system and immune response and may have ultimately led to inflammation.

Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.

Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2). Rats were then subjected to either a bout of acute exercise or 4weeks of chronic treadmill running (5days/week) and cognitive behavioural testing. Acute exercise elevated ketone plasma concentration 1h following exercise. Hepatic HMGCS2 knockdown, verified by protein expression, reduced ketone plasma concentration 1h after acute exercise and 48h after chronic exercise. Proteomic analysis and enrichment of the frontal cortex revealed hepatic HMGCS2 knockdown reduced markers of mitochondrial function 1h after acute exercise. HMGCS2 knockdown significantly reduced state 3 complex I+II respiration in isolated mitochondria from the frontal cortex after chronic exercise. Spatial memory and protein markers of synaptic plasticity were significantly reduced by HMGCS2 knockdown. These deficiencies were prevented by chronic endurance exercise training. In summary, these are the first data to propose that hepatic ketogenesis is required to maintain cognition and mitochondrial function, irrespective of training status, and that endurance exercise can overcome neuropathology caused by insufficient hepatic ketogenesis. These results establish a mechanistic link between liver and brain health that enhance our understanding of how peripheral tissue metabolism influences brain health. KEY POINTS: Decades of literature demonstrate endurance exercise to be neuroprotective. Whether neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. This study provides the first set of data that suggest hepatic ketogenesis is required to maintain cognition, synaptic plasticity and mitochondrial function. These data indicate endurance exercise can protect against cognitive decline caused by compromised hepatic ketogenesis. These results establish a mechanistic link between liver and brain function, prompting further investigation of how hepatic metabolism influences brain health.

Permeable and Durable Liquid-Metal Fiber Mat as Implantable Physiological Electrodes with Long-Term Biocompatibility.

Implantable physiological electrodes provide unprecedented opportunities for real-time and uninterrupted monitoring of biological signals. Most implantable electronics adopt thin-film substrates with low permeability that severely hampers tissue metabolism, impeding their long-term biocompatibility. Recent innovations have seen the advent of permeable electronics through the strategic modification of liquid metals (LMs) onto porous substrates. However, the durability of these electronics is limited by the inherent poor wettability of LMs, particularly within the intricate 3D skeleton of the porous substrate. Herein, the study reports a spatial wettability tuning strategy that solves the wettability issue of LMs within the porous substrates, enabling the LM physiological electrodes with high durability and long-term biocompatibility. The study demonstrates the use of the electrodes as implantable neural interface to realize in vivo acquisition of electrocardiograph and electrocorticogram signals with long-term biocompatibility and high signal-to-noise ratio. This work demonstrates a promising direction for rational design of durable implantable bioelectronics with long-term biocompatibility.