Extraction of high quality and high yield RNA from frozen EDTA blood.

Peripheral blood RNA profiling, which can reveal systemic changes in gene expression and immune responses to disease onset and progression, is a powerful tool for diagnosis and biomarker discovery. This technique usually requires high quality RNA, which is only obtainable from fresh blood, or frozen blood that has been collected in special RNA-stabilisation systems. The current study aimed to develop a novel protocol to extract high quality RNA from frozen blood that had been collected in the conventional EDTA tubes. We determined that thawing EDTA blood in the presence of cell lysis/RNA stabilisation buffers (Paxgene or Nucleospin) significantly improved RNA quality (RIN) from below 5 to above 7, which to date has not been shown possible. The EDTA-Nucleospin protocol resulted in 5 times higher yield than the EDTA-Paxgene-PreAnalytix method. The average RIN and mRNA expression levels of five different genes including 18 s, ACTB, MCP1, TNFa and TXNIP using this protocol were also indifferent to those from Paxgene blood, suggesting similar RNA quality and blood transcriptome. Moreover, the protocol allows DNA to be extracted simultaneously. In conclusion, we have developed a practical and efficient protocol to extract high quality, high yield RNA from frozen EDTA blood.

Nutrition and Developmental Origins of Kidney Disease.

The developmental programming hypothesis proposes that adverse environmental insults during critical developmental periods increase the risk of diseases later in life. The kidneys are deemed susceptible to such a process, although the exact mechanisms remain elusive. Many factors have been reported to contribute to the developmental origin of chronic kidney diseases (CKD), among which peri-gestational nutrition has a central role, affecting kidney development and metabolism. Physiologically, the link between malnutrition, reduced glomerular numbers, and increased blood pressure is key in the developmental programming of CKD. However, recent studies regarding oxidative stress, mitochondrial dysfunction, epigenetic modifications, and metabolic changes have revealed potential novel pathways for therapeutic intervention. This review will discuss the role of imbalanced nutrition in the development of CKD.

Effect of E-Vaping on Kidney Health in Mice Consuming a High-Fat Diet.

High-fat diet (HFD) consumption and tobacco smoking are risk factors for chronic kidney disease. E-cigarettes have gained significant popularity among younger populations worldwide, especially among overweight individuals. It is unclear whether vaping interacts with HFD consumption to impact renal health. In this study, Balb/c mice (male, 7 weeks old) were fed a pellet HFD (43% fat, 20 kJ/g) for 16 weeks when exposed to nicotine or nicotine-free e-vapour from weeks 11 to 16. While HFD alone increased collagen Ia and IV depositions, it did not cause significant oxidative stress and inflammatory responses in the kidney itself. On the other hand, e-vapour exposure alone increased oxidative stress and damaged DNA and mitochondrial oxidative phosphorylation complexes without significant impact on fibrotic markers. However, the combination of nicotine e-vapour and HFD increased inflammatory responses, oxidative stress-induced DNA injury, and pro-fibrotic markers, suggesting accelerated development of renal pathology. Nicotine-free e-vapour exposure and HFD consumption suppressed the production of mitochondrial OXPHOS complexes and extracellular matrix protein deposition, which may cause structural instability that can interrupt normal kidney function in the future. In conclusion, our study demonstrated that a HFD combined with e-cigarette vapour exposure, especially when containing nicotine, can increase susceptibility to kidney disease.

Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis.

Renal fibrosis is the final common pathophysiological pathway in chronic kidney disease (CKD) regardless of the underlying cause of kidney injury. Tubulointerstitial fibrosis (TIF) is considered to be the key pathological predictor of CKD progression. Currently, the gold-standard tool to identify TIF is kidney biopsy, an invasive method that carries risks. Non-invasive diagnostics rely on an estimation of glomerular filtration rate and albuminuria to assess kidney function, but these fail to diagnose early CKD accurately or to predict progressive decline in kidney function. In this review, we summarize the current and emerging molecular biomarkers that have been studied in various clinical settings and in animal models of kidney disease and that are correlated with the degree of TIF. We examine the potential of these biomarkers to diagnose TIF non-invasively and to predict disease progression. We also examine the potential of new technologies and non-invasive diagnostic approaches in assessing TIF. Limitations of current and potential biomarkers are discussed and knowledge gaps identified.

E-Cigarette Vapour Alters High-Fat Diet-Induced Systemic Inflammatory Responses but Has No Effect on High-Fat Diet-Induced Changes in Gut Microbiota.

BACKGROUND: The gut microbiome, which can be altered by different diets or smoking, has been implicated in the pathogenesis of lung conditions. E-cigarette vaping is now recognised to have detrimental health effects, with several of these being similar to cigarette smoking. However, whether e-cigarettes can alter high-fat diet (HFD)-induced systemic effects and gut microbiota is unknown. In this study, we investigated the effects of HFD in the absence/presence of e-cigarette exposure on systemic inflammation, lipid metabolic markers, and the gut microbiome. METHODS: Mice were fed a HFD (or chow) in the absence/presence of e-vapour exposure (±nicotine) and serum inflammation, lipid levels, and microbial diversity were assessed. RESULTS: HFD increased the circulating levels of both triglycerides and non-esterified fatty acids, which were significantly reduced by e-vapour exposure in HFD-fed mice. Serum TNF-α was increased by HFD consumption or e-vapour. HFD had a significant effect on microbial diversity, but there were no additional effects of e-vapour exposure. CONCLUSIONS: This study highlights both similarities and differences in how the body responds to e-cigarette vapours, and it is therefore likely that the long-term sequelae of e-cigarette vapour exposure/vaping might not involve the significant alteration of the gut microbiome.

Deciphering the Kidney Matrisome: Identification and Quantification of Renal Extracellular Matrix Proteins in Healthy Mice.

Precise characterization of a tissue's extracellular matrix (ECM) protein composition (matrisome) is essential for biomedicine. However, ECM protein extraction that requires organ-specific optimization is still a major limiting factor in matrisome studies. In particular, the matrisome of mouse kidneys is still understudied, despite mouse models being crucial for renal research. Here, we comprehensively characterized the matrisome of kidneys in healthy C57BL/6 mice using two ECM extraction methods in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS), protein identification, and label-free quantification (LFQ) using MaxQuant. We identified 113 matrisome proteins, including 22 proteins that have not been previously listed in the Matrisome Database. Depending on the extraction approach, the core matrisome (structural proteins) comprised 45% or 73% of kidney ECM proteins, and was dominated by glycoproteins, followed by collagens and proteoglycans. Among matrisome-associated proteins, ECM regulators had the highest LFQ intensities, followed by ECM-affiliated proteins and secreted factors. The identified kidney ECM proteins were primarily involved in cellular, developmental and metabolic processes, as well as in molecular binding and regulation of catalytic and structural molecules' activity. We also performed in silico comparative analysis of the kidney matrisome composition in humans and mice based on publicly available data. These results contribute to the first reference database for the mouse renal matrisome.

Investigating the Regulatory Process, Safety, Efficacy and Product Transparency for Nutraceuticals in the USA, Europe and Australia.

Increased numbers of patients with chronic conditions use nutraceuticals or food-based therapeutics. However, to date, there is no global consensus on the regulatory processes for nutraceuticals. With the increased use, issues of quality and safety have also arisen. This review summarises the current regulations held for nutraceuticals in the USA, European and Australian jurisdictions using regulatory authority sites and databases. The efficacy and safety concerns, product development, gaps in regulation and challenges in ensuring product authenticity are also summarised. The data highlight the complexity that the globalisation of nutraceuticals brings with respect to challenges in regulation and associated claims regarding efficacy and safety. The development of an effective system with integrity is needed to increase vertical collaboration between consumers, healthcare practitioners, and government agencies and the development of international risk assessment criteria and botanical compendia. This will help in greater transparency and improved trust in the process and products. Emerging technologies could play a role in improving systems engineering by information sharing and leveraging the strengths of different countries. In conclusion, nutraceuticals have been poorly regulated leading to spurious claims based on little or no real evidence. This makes it difficult to separate meaningful results from poor data. More stringent regulation and an effective system of integrity are required to ensure efficacy and safety and enable the adequate monitoring and increase consumer and healthcare professionals' confidence.

Maternal Weight Intervention in the Perinatal Period Improves Liver Health in the Offspring of Mothers with Obesity.

Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance (p < 0.001) and hepatic expression of markers of inflammation (p < 0.001), oxidative stress (p < 0.05), and fibrosis (p < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.

Sex-Dependent Responses to Maternal Exposure to PM2.5 in the Offspring.

Objective: Particulate matter (PM) with a diameter of 2.5 µm or less (PM2.5) can cross the blood-placental barrier causing adverse foetal outcomes. However, the impact of maternal exposure to low-levels of PM2.5 on liver health and the metabolic profile is unclear. This study aimed to investigate hepatic responses to long-term gestational low-dose PM2.5 exposure, and whether the removal of PM after conception can prevent such effects. Method: Female Balb/c mice (8 weeks) were exposed to PM2.5 (5 µg/day) for 6 weeks prior to mating, during gestation and lactation to model living in a polluted environment (PM group). In a sub-group, PM2.5 exposure was stopped post-conception to model mothers moving to areas with clean air (pre-gestation, Pre) group. Livers were studied in 13-week old offspring. Results: Female offspring in both PM and Pre groups had increased liver triglyceride and glycogen levels, glucose intolerance, but reduced serum insulin and insulin resistance. Male offspring from only the Pre group had increased liver and serum triglycerides, increased liver glycogen, glucose intolerance and higher fasting glucose level. Markers of oxidative stress and inflammation were increased in females from PM and Pre groups. There was also a significant sex difference in the hepatic response to PM2.5 with differential changes in several metabolic markers identified by proteomic analysis. Conclusions: Maternal PM exposure exerted sex-dependent effects on liver health with more severe impacts on females. The removal of PM2.5 during gestation provided limited protection in the offspring's metabolism regardless of sex.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Inhaled or Ingested, Which Is Worse, E-Vaping or High-Fat Diet?

Long term e-cigarette vaping induces inflammation, which is largely nicotine independent. High-fat diet (HFD) consumption is anoter cause of systemic low-grade inflammation. The likelihood of using e-cigarettes as a weight control strategy is concomitant with the increase in obesity. In Australia, only nicotine-free e-fluid is legal for sale. Therefore, this study aimed to investigate how nicotine-free e-cigarette vapour exposure affects inflammatory responses in mice with long term HFD consumption. Mice were fed a HFD for 16 weeks, while in the last 6 weeks, half of the chow and HFD groups were exposed to nicotine-free e-vapour, while the other half to ambient air. Serum, lung, liver and epididymal fat were collected to measure inflammatory markers. While both e-vapour exposure and HFD consumption independently increased serum IFN-γ, CX3CL1, IL-10, CCL20, CCL12, and CCL5 levels, the levels of IFN-γ, CX3CL1, and IL-10 were higher in mice exposed to e-vapour than HFD. The mRNA expression pattern in the epididymal fat mirrors that in the serum, suggesting the circulating inflammatory response to e-vapour is from the fat tissue. Of the upregulated cytokines in serum, none were found to change in the lungs. The anti-inflammatory cytokine IL-10 was increased by combining e-vapour and HFD in the liver. We conclude that short-term nicotine-free e-vapour is more potent than long term HFD consumption in causing systemic inflammation. Future studies will be needed to examine the long-term health impact of nicotine-free e-cigarettes.

Fimbristylis ovata and Artemisia vulgaris extracts inhibited AGE-mediated RAGE expression, ROS generation, and inflammation in THP-1 cells.

Advanced glycation end products (AGEs) can induce inflammatory signaling pathways through the receptor for AGEs (RAGE). Targeting RAGE could be a therapeutic strategy for treating chronic inflammation mediated by the AGE-RAGE axis. This study aimed to investigate the effects of Fimbristylis ovata and Artemisia vulgaris extracts on AGE-RAGE signaling and AGE-mediated oxidative stress and inflammation in THP-1 cells. F. ovata and A. vulgaris were extracted by a Soxhlet extraction, and antioxidant capacity was evaluated using DPPH and ABTS assays. The human monocytic cell line THP-1 was treated with AGE (600 µg/ml) with and without F. ovata and A. vulgaris extracts (100 µg/ml). The mitochondria-targeting antioxidant MitoQ (2 µg/ml) was used as a positive control. Cell viability, ROS generation, RAGE, AGE-RAGE signaling pathway components, and inflammatory cytokine levels were analyzed. F. ovata and A. vulgaris extracts showed antioxidative effects in non-cell-based assays. Treatment of THP-1 cells with AGE significantly increased the protein levels of RAGE and significantly increased the mRNA expression of cytokines, including TNF-α, IL-1ß, and IL-6. AGEs induced the generation of ROS and levels of signaling molecules downstream of RAGE, including phosphorylated and total Erk1/2, JNK, and p38 MAPK, although not significantly. F. ovata and A. vulgaris extracts significantly decreased the protein levels of RAGE and significantly decreased the mRNA levels of cytokines. In conclusion, this study revealed that F. ovata and A. vulgaris extracts exert anti-inflammatory effects through the AGE-RAGE axis. However, details on this anti-inflammatory effect through AGE-RAGE signaling should be further investigated. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-021-00114-0.

Exfoliated Kidney Cells from Urine for Early Diagnosis and Prognostication of CKD: The Way of the Future?

Chronic kidney disease (CKD) is a global health issue, affecting more than 10% of the worldwide population. The current approach for formal diagnosis and prognostication of CKD typically relies on non-invasive serum and urine biomarkers such as serum creatinine and albuminuria. However, histological evidence of tubulointerstitial fibrosis is the 'gold standard' marker of the likelihood of disease progression. The development of novel biomedical technologies to evaluate exfoliated kidney cells from urine for non-invasive diagnosis and prognostication of CKD presents opportunities to avoid kidney biopsy for the purpose of prognostication. Efforts to apply these technologies more widely in clinical practice are encouraged, given their potential as a cost-effective approach, and no risk of post-biopsy complications such as bleeding, pain and hospitalization. The identification of biomarkers in exfoliated kidney cells from urine via western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence techniques, measurement of cell and protein-specific messenger ribonucleic acid (mRNA)/micro-RNA and other techniques have been reported. Recent innovations such as multispectral autofluorescence imaging and single-cell RNA sequencing (scRNA-seq) have brought additional dimensions to the clinical application of exfoliated kidney cells from urine. In this review, we discuss the current evidence regarding the utility of exfoliated proximal tubule cells (PTC), podocytes, mesangial cells, extracellular vesicles and stem/progenitor cells as surrogate markers for the early diagnosis and prognostication of CKD. Future directions for development within this research area are also identified.

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity.

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.

Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.

AIM: To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD). METHODS: From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed. RESULTS: The HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine. CONCLUSION: Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic variables or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients.

Effects of air pollution on human health - Mechanistic evidence suggested by in vitro and in vivo modelling.

Airborne particulate matter (PM) comprises both solid and liquid particles, including carbon, sulphates, nitrate, and toxic heavy metals, which can induce oxidative stress and inflammation after inhalation. These changes occur both in the lung and systemically, due to the ability of the small-sized PM (i.e. diameters ≤2.5 µm, PM2.5) to enter and circulate in the bloodstream. As such, in 2016, airborne PM caused ∼4.2 million premature deaths worldwide. Acute exposure to high levels of airborne PM (eg. during wildfires) can exacerbate pre-existing illnesses leading to hospitalisation, such as in those with asthma and coronary heart disease. Prolonged exposure to PM can increase the risk of non-communicable chronic diseases affecting the brain, lung, heart, liver, and kidney, although the latter is less well studied. Given the breadth of potential disease, it is critical to understand the mechanisms underlying airborne PM exposure-induced disorders. Establishing aetiology in humans is difficult, therefore, in-vitro and in-vivo studies can provide mechanistic insights. We describe acute health effects (e.g. exacerbations of asthma) and long term health effects such as the induction of chronic inflammatory lung disease, and effects outside the lung (e.g. liver and renal change). We will focus on oxidative stress and inflammation as this is the common mechanism of PM-induced disease, which may be used to develop effective treatments to mitigate the adverse health effect of PM exposure.

Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice.

Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild-moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease's prognostication.

Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation.

BACKGROUND: Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize-resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the gut microbiota in alignment with modulation of the immune system status. RESULTS: HAMSAB supplement was administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. CONCLUSION: Changes in gut microbiota composition, function, and immune profile following 6 weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance, and improve glycemic control for the treatment of T1D. TRIAL REGISTRATION: ACTRN12618001391268. Registered 20 August 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792 Video Abstract.

Correction: A Cationic-Independent Mannose 6-Phosphate Receptor Inhibitor (PXS64) Ameliorates Kidney Fibrosis by Inhibiting Activation of Transforming Growth Factor-ß1.

[This corrects the article DOI: 10.1371/journal.pone.0116888.].

Differential Effects of 'Vaping' on Lipid and Glucose Profiles and Liver Metabolic Markers in Obese Versus Non-obese Mice.

Tobacco smoking increases the risk of metabolic disorders due to the combination of harmful chemicals, whereas pure nicotine can improve glucose tolerance. E-cigarette vapour contains nicotine and some of the harmful chemicals found in cigarette smoke at lower levels. To investigate how e-vapour affects metabolic profiles, male Balb/c mice were exposed to a high-fat diet (HFD, 43% fat, 20kJ/g) for 16weeks, and e-vapour in the last 6weeks. HFD alone doubled fat mass and caused dyslipidaemia and glucose intolerance. E-vapour reduced fat mass in HFD-fed mice; only nicotine-containing e-vapour improved glucose tolerance. In chow-fed mice, e-vapour increased lipid content in both blood and liver. Changes in liver metabolic markers may be adaptive responses rather than causal. Future studies can investigate how e-vapour differentially affects metabolic profiles with different diets.