• Adipogenesis
• Cerium
• Human bone marrow derived mesenchymal stromal cells
• Osteogenesis
• Proliferation
• Reactive oxygen species
• Viability

• adipogenesis
• autophagy
• immune responses
• inflammation
• oxidative stress

• Adipogenesis/physiology
• Humans
• Autophagy/physiology
• Oxidative Stress/physiology
• Inflammation/metabolism
• Inflammation/pathology
• Animals
• Adipocytes/metabolism
• Adipocytes/pathology
• Obesity/metabolism
• Obesity/pathology
• Adipose Tissue/metabolism
• Adipose Tissue/pathology

• Adipogenic differentiation
• Epigenetic regulation
• Mesenchymal stem cell
• Noncoding RNA
• Signaling pathway

• adipocytes
• body composition
• fat mass
• lean mass
• oestrogen deficiency
• traditional Chinese medicine

• Humans
• Rats
• Female
• Animals
• Infant
• Bone Marrow
• Rats, Sprague-Dawley
• Adiposity
• Antioxidants/pharmacology
• Obesity
• Oxidation-Reduction
• Ovariectomy/adverse effects
• Bone Density

• Brown adipocytes
• Differentiation
• Heme
• Histone methylation
• Oxidative phosphorylation

• Adipogenesis/genetics
• Histones/metabolism
• Electron Transport Complex I/metabolism
• Demethylation
• Cell Differentiation

• adipogenesis
• fructose
• glucose
• inosine
• mesenchymal stem cells
• reactive oxygen species

• Ca2+ oscillations
• adipocytes
• hemichannels
• lipolysis

• Bioinformatics
• Long non-coding RNA
• Mesenchymal stem cell
• NGS analysis
• RNAseq
• Transcriptomics

• Base Sequence
• Computational Biology
• Mesenchymal Stem Cells
• RNA, Long Noncoding/genetics
• Sequence Analysis, RNA

• 18-CE45-0020-02 Agence Nationale de la Recherche
• ANR-10-INBS-09 Agence Nationale de la Recherche
• 2017-EM24 Canceropole Grand-Sud-Ouest

• Na,K-ATPase
• RNA sequencing
• adipocytes
• chronic renal failure
• oxidative stress
• uremic cardiomyopathy

• 3T3 Cells
• Adipocytes/metabolism
• Animals
• Gene Regulatory Networks
• Indican/metabolism
• Lipoproteins, LDL/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress
• Peptide Fragments/genetics
• Peptide Fragments/metabolism
• Sodium-Potassium-Exchanging ATPase/genetics
• Sodium-Potassium-Exchanging ATPase/metabolism
• Transcriptome

• HL55601 NIH HHS
• 1R15DK106666 NIH HHS
• HL071556 NIH HHS
• HL109015 NIH HHS
• HL34300 NIH HHS
• U54 GM104942 NIGMS NIH HHS
• R15 HL150721 NHLBI NIH HHS
• HL105649 NIH HHS

Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.

• Colon cancer
• Genotoxicity
• Mutagenicity
• Nitrosylated heme
• Processed red meat

• Animals
• BALB 3T3 Cells
• Caco-2 Cells
• Carcinogenesis/chemically induced
• Cell Line
• Cell Transformation, Neoplastic/drug effects
• Comet Assay
• Cricetinae
• DNA Damage/drug effects
• Heme/chemistry
• Heme/toxicity
• Humans
• Intestinal Neoplasms/chemically induced
• Mice
• Mutagenesis
• Mutation
• Nitric Oxide/chemistry
• Nitric Oxide/toxicity
• Red Meat/toxicity
• Risk Factors
• Single-Cell Analysis

• artificial sweeteners
• diet soda
• inflammation
• metabolism
• obesity
• sucralose

• Adipocyte inflammation
• Bilirubin
• Fatty liver
• Hyperbilirubinemia
• Hypertension
• Obesity

Background: Angiotensin II (Ang II), released by the renin–angiotensin–aldosterone system (RAAS), contributes to the modulatory role of the RAAS in adipose tissue dysfunction. Investigators have shown that inhibition of AngII improved adipose tissue function and insulin resistance in mice with metabolic syndrome. Heme Oxygenase-1 (HO-1), a potent antioxidant, has been demonstrated to improve oxidative stress and adipocyte phenotype. Molecular effects of high oxidative stress include suppression of sirtuin-1 (SIRT1), which is amenable to redox manipulations. The mechanisms involved, however, in these metabolic effects of the RAAS remain incompletely understood. Hypothesis: We hypothesize that AngII-induced oxidative stress has the potential to suppress adipocyte SIRT1 via down regulation of HO-1. This effect of AngII will, in turn, upregulate mineralocorticoid receptor (MR). The induction of HO-1 will rescue SIRT1, hence improving oxidative stress and adipocyte phenotype. Methods and Results: We examined the effect of AngII on lipid accumulation, oxidative stress, and inflammatory cytokines in mouse pre-adipocytes in the presence and absence of cobalt protoporphyrin (CoPP), HO-1 inducer, tin mesoporphyrin (SnMP), and HO-1 inhibitor. Our results show that treatment of mouse pre-adipocytes with AngII increased lipid accumulation, superoxide levels, inflammatory cytokine levels, interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), and adiponectin levels. This effect was attenuated by HO-1 induction, which was further reversed by SnMP, suggesting HO-1 mediated improvement in adipocyte phenotype. AngII-treated pre-adipocytes also showed upregulated levels of MR and suppressed SIRT1 that was rescued by HO-1. Subsequent treatment with CoPP and SIRT1 siRNA in mouse pre-adipocytes increased lipid accumulation and fatty acid synthase (FAS) levels, suggesting that beneficial effects of HO-1 are mediated via SIRT1. Conclusion: Our study demonstrates for the first time that HO-1 has the ability to restore cellular redox, rescue SIRT1, and prevent AngII-induced impaired effects on adipocytes and the systemic metabolic profile.

• adipocytes
• angiotensin II
• heme oxygenase 1
• mineralocorticoid receptor
• oxidative stress
• sirtuin 1

• Adipocytes
• Lipid metabolism
• Mitochondria
• Peroxisomes
• Redox

• Adipocytes/metabolism
• Adipogenesis
• Energy Metabolism
• Homeostasis
• Lipid Metabolism
• Metabolic Networks and Pathways
• Mitochondria/metabolism
• Models, Biological
• Oxidation-Reduction
• Peroxisomes/metabolism
• Reactive Oxygen Species/metabolism
• Signal Transduction

• P30 DK056341 NIDDK NIH HHS
• P30 DK092950 NIDDK NIH HHS
• R01 DK097608 NIDDK NIH HHS

• TAMRA+ cells
• cancer stem cell
• carcinogenesis
• genes-markers of stemness
• hypoxia
• induction of pluripotency
• oxidative stress
• xenobiotics

Background: Oxidant stress plays a key role in the development of chronic kidney disease (CKD). Experimental CKD leads to accumulation of uremic toxins (UT) in the circulation resulting in increased ROS production, which in turn, is known to activate the Na/K-ATPase/ROS amplification loop. Studies in a murine model of obesity have shown that increased oxidative stress in plasma is due to increased ROS and cytokine production from dysfunctional adipocytes. Therefore, we hypothesized that adipocytes exposed to UTs will activate the Na/K-ATPase oxidant amplification loop causing redox imbalance and phenotypic alterations in adipocytes. We also aimed to demonstrate that the Na/K-ATPase signaling antagonist, pNaKtide, attenuates these pathophysiological consequences. Methods: In the first set of experiments, 3T3-L1 murine pre-adipocytes were treated with varying concentrations of UTs, indoxyl sulfate (IS) (50, 100 and 250 µM) and p-cresol (50, 100 and 200 µM), with or without pNaKtide (0.7 µM) for five days in adipogenic media, followed by Oil Red O staining to study adipogenesis. RT-PCR analysis was performed to study expression of adipogenic, apoptotic and inflammatory markers, while DHE staining evaluated the superoxide levels in UT treated cells. In a second set of experiments, visceral fat was obtained from the West Virginian population. MSCs were isolated and cultured in adipogenic media for 14 days, which was treated with indoxyl sulfate (0, 25, 50 and 100 µM) with or without pNaKtide (1 µM). MSC-derived adipocytes were evaluated for morphological and molecular analysis of the above markers. Results: Our results demonstrated that 3T3-L1 cells and MSCs-derived adipocytes, treated with UTs, exhibited a significant decrease in adipogenesis and apoptosis through activation of the Na/K-ATPase/ROS amplification loop. The treatment with pNaKtide in 3T3-L1 cells and MSC-derived adipocytes negated the effects of UTs and restored cellular redox in adipocytes. We noted a varying effect of pNaKtide, in adipocytes treated with UTs, on inflammatory markers, adipogenic marker and superoxide levels in 3T3-L1 cells and MSC-derived adipocytes. Conclusions: This study demonstrates for the first time that the Na/K-ATPase/ROS amplification loop activated by elevated levels of UTs has varying effect on phenotypic alterations in adipocytes in various in vitro models. Thus, we propose that, if proven in humans, inhibition of Na/K-ATPase amplification of oxidant stress in CKD patients may ultimately be a novel way to combat adipocyte dysfunction and metabolic imbalance in these patients.

• CKD
• Na/K-ATPase signaling
• ROS
• adipocytes
• oxidative stress
• uremic toxins

Aging has been associated with a series of pathophysiological processes causing general decline in the overall health of the afflicted population. The cumulative line of evidence suggests an important role of oxidative stress in the development and progression of the aging process and metabolic abnormalities, exacerbating adipocyte dysfunction, cardiovascular diseases, and associated complications at the same time. In recent years, robust have established the implication of Na/K-ATPase signaling in causing oxidative stress and alterations in cellular mechanisms, in addition to its distinct pumping function. Understanding the underlying molecular mechanisms and exploring the possible sources of pro-oxidants may allow for developing therapeutic targets in these processes and formulate novel intervention strategies for patients susceptible to aging and associated complications, such as obesity and cardiovascular disease. The attenuation of oxidative stress with targeted treatment options can improve patient outcomes and significantly reduce economic burden.

• Na/K-ATPase signaling
• aging
• cardiovascular disease
• obesity
• oxidative stress

• antioxidant gene response
• heme
• mesenchymal stem cell
• stem cells

Hypercholesterolemia increases and exacerbates stress signals leading also to liver damage (LD) and failure. Sirtuin1 (SIRT1) is involved in lifespan extension and it plays an essential role in hepatic lipid metabolism. However, its involvement in liver hypercholesterolemic damage is not yet completely defined. This in vivo study evaluated the role of SIRT1 in the hypercholesterolemic-related LD and, then, investigated how oral supplementation of melatonin, pleiotropic indoleamine, may be protective. Control mice and apolipoprotein E-deficient mice (ApoE^−/−) of 6 and 15 weeks of age were treated or not treated with melatonin at the dose of 10 mg/kg/day for 9 weeks. In this study, we evaluated serum biochemical markers, liver SIRT1 expression, and oxidative stress markers. We observed that hypercholesterolemia increased significantly serum cholesterol and triglycerides, reduced significantly liver SIRT1, and, in turn, induced hepatic oxidative stress in untreated ApoE^−/− mice with respect to control mice. Interestingly, melatonin treatment improved serum biochemical markers and hepatic morphological impairment and inhibited oxidative stress through its antioxidant properties and also by SIRT1 upregulation. In summary, melatonin oral supplementation may represent a new protective approach to block hypercholesterolemic liver alterations involving also a SIRT1-dependent mechanism.

• Adipogenesis/physiology
• Animals
• Biosynthetic Pathways/physiology
• Heme/metabolism
• Humans
• Male
• Middle Aged
• Mitochondria/metabolism
• Rats
• Rats, Wistar
• Weight Gain

Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress response system which reduces oxidative stress. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues from lean and obese mice. Obese mice exhibited hyperglycemia (p < 0.05); increased levels of proinflammatory cytokines (MCP-1, IL-6, p < 0.05); oxidative stress (p < 0.05); and increased hepatic hepcidin levels (p < 0.05). Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice (p < 0.05). However, this effect is accompanied by a significant decline in ferritin expression. Additionally, there are reduced insulin receptor phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1. Cobalt protoporphyrin- (CoPP-) induced HO-1 upregulation in obese mice reversed these alterations (p < 0.05), while attenuating hepatic hepcidin levels. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP) (p < 0.05). Our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin.

Hemin is a breakdown product of hemoglobin. It has been reported that the injection of hemin improves lipid metabolism and insulin sensitivity in various genetic models. However, the effect of hemin supplementation in food on lipid metabolism and insulin sensitivity is still unclear, and whether hemin directly affects cellular insulin sensitivity is yet to be elucidated. Here we show that hemin enhances insulin-induced phosphorylation of insulin receptors, Akt, Gsk3β, FoxO1 and cytoplasmic translocation of FoxO1 in cultured primary hepatocytes under insulin-resistant conditions. Furthermore, hemin diminishes the accumulation of triglyceride and increases in free fatty acid content in primary hepatocytes induced by palmitate. Oral administration of hemin decreases body weight, energy intake, blood glucose and triglyceride levels, and improves insulin and glucose tolerance as well as hepatic insulin signaling and hepatic steatosis in male mice fed a high-fat diet. In addition, hemin treatment decreases the mRNA and protein levels of some hepatic genes involved in lipogenic regulation, fatty acid synthesis and storage, and increases the mRNA level and enzyme activity of CPT1 involved in fatty acid oxidation. These data demonstrate that hemin can improve lipid metabolism and insulin sensitivity in both cultured hepatocytes and mice fed a high-fat diet, and show the potential beneficial effects of hemin from food on lipid and glucose metabolism.

• hemin
• hepatic steatosis
• insulin resistance
• lipid metabolism

• Animals
• Biomarkers/blood
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Cells, Cultured
• Diet, High-Fat/adverse effects
• Dose-Response Relationship, Drug
• Energy Metabolism/drug effects
• Forkhead Box Protein O1/metabolism
• Gene Expression Regulation
• Glucose Intolerance/blood
• Glucose Intolerance/etiology
• Glucose Intolerance/genetics
• Glucose Intolerance/prevention & control
• Glycogen Synthase Kinase 3 beta/metabolism
• Hemin/pharmacology
• Hepatocytes/drug effects
• Hepatocytes/metabolism
• Insulin/pharmacology
• Insulin Resistance
• Lipid Metabolism/drug effects
• Lipid Metabolism/genetics
• Male
• Mice, Inbred C57BL
• Palmitic Acid/pharmacology
• Phosphorylation
• Protein Transport
• Proto-Oncogene Proteins c-akt/metabolism
• Receptor, Insulin/agonists
• Receptor, Insulin/metabolism
• Signal Transduction/drug effects
• Time Factors
• Triglycerides/blood
• Weight Loss/drug effects

Iron status is known to be associated with the physiology of adipose tissue (AT). We aimed to investigate AT heme and expression of heme exporter (FLVCR1) in association with obesity and type 2 diabetes (T2D). Substantial amounts of FLVCR1 mRNA and protein levels were detected in AT, being significantly increased in subjects with T2D, and positively correlated with fasting glucose, fasting triglycerides and with circulating markers of iron stores (serum ferritin, blood hemoglobin and hematocrit). In both visceral (VAT) and subcutaneous AT (SAT), increased heme levels were found in subjects with T2D. Reinforcing these associations, FLVCR1 mRNA levels were positively linked to fasting glucose in an independent cohort. Longitudianlly, the percent change of FLVCR1 positively correlated with the percent change in fasting glucose (r = 0.52, p = 0.03) after bariatric surgery-induced weight loss. High-fat diet-induced weight gain in rats did not result in significant changes in AT Flvcr1 mRNA but, remarkably, the expression of this gene positively correlated with fasting glucose and negatively with insulin sensitivity (QUICKI). Altogether, these findings showed a direct association between FLVCR1 mRNA levels and hyperglycemia, suggesting that increased adipose tissue heme exportation might disrupt, or is the consequence of, impaired systemic glucose metabolism during the progression to T2D.

• DPSCs
• Osteogenic differentiation
• SIRT1
• Wnt/β-catenin

• Epoxyeicosatrienoic acid
• HO-1
• Metabolic dysfunction

• Adipogenesis
• Hydroxytyrosol
• Mesenchymal stromal/stem cells
• Osteoblastogenesis
• Osteoporosis

Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs), enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

• genes expression
• metabolism
• obesity
• single nucleotide polymorphisms
• sirtuins

• Adipocytes/cytology
• Adipocytes/metabolism
• Adipogenesis/genetics
• Animals
• Cell Differentiation
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Glucose/metabolism
• Humans
• Insulin/metabolism
• Insulin Secretion
• Lipid Metabolism/genetics
• Obesity/genetics
• Polymorphism, Single Nucleotide
• Sirtuins/chemistry
• Sirtuins/genetics
• Sirtuins/physiology

• Adipocyte differentiation
• Antioxidant
• Epigenetic modulation
• Obesity
• Post-translational modification
• ROS
• Redox
• Transcription factor

• Adipocytes/cytology
• Adipogenesis/physiology
• Animals
• Cell Differentiation
• Humans
• Obesity/physiopathology
• Oxidation-Reduction

• Na/K-ATPase
• adipogenesis
• high-fat diet
• metabolic syndrome
• oxidative stress
• pNaKtide peptide

• P01 HL034300 NHLBI NIH HHS
• R01 HL105649 NHLBI NIH HHS
• R01 HL109015 NHLBI NIH HHS
• U01 HL071556 NHLBI NIH HHS
• National Institutes of Health (US)
• Brickstreet Foundation
• Huntington Foundation

Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate.

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.

Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression.

• AMP-Activated Protein Kinases/metabolism
• Animals
• Blood Pressure/physiology
• Cells, Cultured
• Diet
• Enzyme Activation
• Fructose/metabolism
• Heme Oxygenase-1/genetics
• Heme Oxygenase-1/metabolism
• Hepatocytes/metabolism
• Insulin Resistance/physiology
• Liver/pathology
• Male
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/pathology
• Oxidative Stress
• PPAR alpha/metabolism
• RNA Interference
• RNA, Small Interfering
• Sirtuin 1/genetics
• Sirtuin 1/metabolism
• Triglycerides/blood
• fas Receptor/metabolism

• P01 HL034300 NHLBI NIH HHS
• R01 HL109015 NHLBI NIH HHS
• U01 HL071556 NHLBI NIH HHS
• 1R01HL109015-01 NHLBI NIH HHS

• Adipocytes/cytology
• Adipocytes/physiology
• Animals
• Cell Differentiation
• Cell Survival
• Cells, Cultured
• Down-Regulation
• Female
• Gene Expression Regulation
• Gene Knockdown Techniques
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/physiology
• Nuclear Receptor Co-Repressor 1/genetics
• Nuclear Receptor Co-Repressor 1/metabolism
• RNA, Small Interfering
• Rats, Wistar

• HO-1
• Sirt1
• nonalcoholic fatty liver disease
• obesity.
• stem cell transplantation

• Animals
• Antioxidants/metabolism
• Blotting, Western
• Diabetes Mellitus, Experimental/metabolism
• Diabetes Mellitus, Experimental/therapy
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/therapy
• Fatty Liver/metabolism
• Fatty Liver/therapy
• Male
• Mice
• Mice, Inbred C57BL
• Sirtuin 1/genetics
• Sirtuin 1/metabolism
• Stem Cell Transplantation

• P01 HL034300 NHLBI NIH HHS
• R01 HL109015 NHLBI NIH HHS

Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT.

• autoimmune diseases
• intra-bone marrow-bone marrow transplantation
• malignant tumors
• mesenchymal stem cell
• rheumatoid arthritis

• butyric acid
• nadph oxidase
• oxidative stress
• rat blood cytosol
• sirtuin-1

• Animals
• Butyric Acid/pharmacology
• Cytosol/drug effects
• Cytosol/metabolism
• Gingiva/metabolism
• Heme/metabolism
• Jugular Veins/pathology
• NAD/metabolism
• NADP/metabolism
• Oxidative Stress/drug effects
• Rats
• Sirtuin 1/metabolism

• pparδ
• ho-1
• adipogenesis
• angiotensin ii
• adiponectin

• Adipocytes/metabolism
• Angiotensin II/pharmacology
• Animals
• Enzyme Activation
• Heme Oxygenase-1/metabolism
• Hypertension, Renovascular/metabolism
• Kidney/metabolism
• PPAR delta/metabolism
• Promoter Regions, Genetic
• Rats
• Rats, Sprague-Dawley
• Renin/blood

• P01 HL034300 NHLBI NIH HHS
• R01 DK056601 NIDDK NIH HHS
• HL-34300 NHLBI NIH HHS
• DK56601 NIDDK NIH HHS