Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal in diabetic patients. However, ...the mechanism by which iron metabolism levels affect DN is poorly understood. This study was designed to evaluate the role of iron-chelator deferoxamine (DFO) in the improvement of DN. Here, we established a DN rat model induced by diets high in carbohydrates and fat and streptozotocin (STZ) injection. Our data demonstrated that DFO treatment for three weeks greatly attenuated renal dysfunction as evidenced by decreased levels of urinary albumin, blood urea nitrogen, and serum creatinine, which were elevated in DN rats. Histopathological observations showed that DFO treatment improved the renal structures of DN rats and preserved podocyte integrity by preventing the decrease of transcripts of nephrin and podocin. In addition, DFO treatment reduced the overexpression of fibronectin 1, collagen I, IL-1β, NF-κB, and MCP-1 in DN rats, as well as inflammatory cell infiltrates and collagenous fibrosis. Taken together, our findings unveiled that iron chelation via DFO injection had a protective impact on DN by alleviating inflammation and fibrosis, and that it could be a potential therapeutic strategy for DN.
Iron exerts significant influences on glucose metabolism. However, the regulatory mechanisms underlying disordered glucose response remains largely unclear. The aim of this study was to examine the ...impact of dietary iron on hepatic gluconeogenesis in mice and in rat liver-derived cells. High iron models of C57BL/6J mice were fed with 1.25 g Fe/kg diets for 9 weeks, and high-iron BRL-3A cell models were treated with 250 μmol/L FeSO4 for 12 h and 24 h. Our data showed that higher iron intake resulted in higher hepatic iron without iron toxicity, and reduced body weight gain with no difference of food intakes. High dietary iron significantly increased 61% of hepatic glycogen deposition, but exhibited impairment in glucose responses in mice. Moreover, high dietary iron suppressed hepatic gluconeogenesis by repressing the expression of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, mice fed with higher iron diets exhibited both decreased AMP-activated protein kinase (AMPK) activity and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) protein levels. Furthermore, in BRL-3A cells, iron treatment increased cellular glucose uptake, and altered gluconeogenesis rhythmically by regulating the activation of AMPK and expression of PGC-1α successively. This study demonstrated that dietary high iron was able to increase hepatic glycogen deposition by enhancement of glucose uptake, and suppress hepatic gluconeogenesis by regulation of AMPK and PGC-1α.
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Iron plays a vital role in the metabolism of adipose tissue. On the one hand, iron is essential for differentiation, endocrine, energy supply and other physiological functions of adipocytes. Iron ...homeostasis affects the progression of many chronic metabolic diseases such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In adipose tissue, iron deficiency is associated with obesity, mainly due to inflammation. Nevertheless, excessive iron in adipose tissue leads to decreased insulin sensitivity owing to mitochondrial dysfunction and adipokine changes. On the other hand, iron has an effect on the thermogenesis of adipocytes. Iron deficiency affects the production of beige fat and the direction of the differentiation of brown fat. In this review, we summarize the current understanding of the crosstalk between iron homeostasis and metabolism in adipose tissue.
Iron plays a vital role in the metabolism of adipose tissue.
Iron homeostasis disorder is associated with the imbalance of lipid metabolism, while the specific interaction remains unclear. In the present study, we investigated the effect of a high-iron diet on ...lipid metabolism in mice. The C57BL/6 mice were fed with a normal diet (WT) or a high-iron diet (WT + Fe) for 12 weeks. We found that mice in the WT + Fe group showed a significant decrease in body weight gain, body fat and lipid accumulation of liver when compared with mice in the WT group. Accordingly, serum total cholesterol and triglyceride levels were both reduced in mice with a high-iron diet. Moreover, mice in the WT + Fe group exhibited a significant decrease in expression of genes regulating adipogenesis and adipocyte differentiation, and a significant increase in expression of fat hydrolysis enzyme genes in both liver and adipose tissues, which was consistent with their dramatic reduction in adipocyte cell size. In addition, a high-iron diet decreased the relative abundance of beneficial bacteria (Akkermansia, Bifidobacterium and Lactobacillus) and increased the relative abundance of pathogenic bacteria (Romboutsia and Erysipelatoclostridium). Thus, our research revealed that a high-iron diet reduced lipid deposition by inhibiting adipogenesis and promoting lipolysis. Altered gut microbial composition induced by a high-iron diet may not play a critical role in regulating lipid metabolism, but might cause unwanted side effects such as intestinal inflammation and damaged villi morphology at the intestinal host–microbe interface. These findings provide new insights into the relationship among iron, lipid metabolism and gut microbiota.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Studies have shown that brood parasites lay their eggs early in the egg-laying sequence of their hosts, providing them with the advantage of earlier hatching. However, common cuckoos (Cuculus ...canorus) appear to parasitize the nests of gray bushchat (Saxicola ferreus) during the late egg-laying stage. The bushchat often abandons parasitized nests in the early stages, but not in the late egg-laying stages, thus favoring late egg-laying by cuckoos. In this study, four experiments were conducted to determine whether gray bushchats employ a nest desertion strategy targeted at cuckoo parasitism. The results showed that nest desertion was significantly correlated with parasitism cues and occurred mainly during the hosts’ early egg-laying stage. Our study provides the first experimental evidence that nest desertion is an anti-parasitic strategy used by hosts in response to cuckoos. Additionally, our experiments demonstrated that the nest desertion is influenced by the trade-offs of investments in different egg-laying stages.
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•Nest desertion by the host is an anti-parasitic strategy against cuckoo parasitism•Nest desertion is influenced by the trade-offs of host investments for their nests•Hosts desert their nests in early egg-laying stage in response to cuckoos
Biological sciences; Ornithology; Evolutionary biology
Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa ...remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h. We found that iron overload caused damage to intestinal morphology with a 64 % reduction in villus height/crypt depth ratio, and microvilli injury in the duodenum. Iron overload mediated epithelial function by inhibiting the expression of nutrient transporters and enhancing the expression of secretory factors in the duodenum. Meanwhile, iron overload inhibited the proliferation of ISCs and regulated their differentiation into secretory mature cells, such as goblet cells, through inhibiting Notch signaling pathway both in mice and enteroid. Furthermore, iron overload caused oxidative stress and ferroptosis in intestinal epithelial cells. In addition, ferroptosis could also inhibit Notch signaling pathway, and affected the proliferation and differentiation of ISCs. These findings reveal the regulatory role of iron overload on the proliferation and differentiation of ISCs, providing a new insight into the internal mechanism of iron overload affecting intestinal health, and offering important theoretical basis for the scientific application of iron nutrition regulation.
Imbalance of iron homeostasis has been involved in clinical courses of metabolic diseases such as type 2 diabetes mellitus, obesity, and nonalcoholic fatty liver, through mechanisms not yet fully ...elucidated. Herein, we evaluated the effect of dietary iron on the development of diabetic syndromes in genetically obese
db/db
mice. Mice (aged 7 weeks) were fed with high-iron (HI) diets (1000 mg/kg chow) or low-iron (LI) diets (12 mg/kg) for 9 weeks. HI diets increased hepatic iron threefold and led to fourfold higher mRNA levels of hepcidin. HI also induced a 60% increase in fasting glucose due to insulin resistance, as confirmed by decreased hepatic glycogen deposition eightfold and a 21% decrease of serum adiponectin level. HI-fed mice had lower visceral adipose tissue mass estimated by epididymal and inguinal fat pad, associated with iron accumulation and smaller size of adipocytes. Gene expression analysis of liver showed that HI diet upregulated gluconeogenesis and downregulated lipogenesis. These results suggested that excess dietary iron leads to reduced mass, increased fasting glucose, decreased adiponectin level, and enhancement of insulin resistance, which indicated a multifactorial role of excess iron in the development of diabetes in the setting of obesity.
In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-α secretion by its ...lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. Moreover, the weak physical association between PTEN and TLR4 in resting RAW264.7 cells increased gradually after the stimulation of LPS. Furthermore, our study showed PTEN decreased LPS-induced Akt activity and upregulated NF- κ B-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF- κ B by its downstream Akt kinase. In summary, our study illustrates the potential signal transduction process of PTEN while stimulated by LPS: by increasing the association of TLR4, PTEN recruits to its phosphoinositide substrate PI(3,4,5)P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream molecule Akt and results in activation of NF- κ B, followed by the secretion of inflammatory mediators TNF-α.
Narciclasine (NCS) is a plant growth inhibitor isolated from the secreted mucilage of Narcissus tazetta bulbs. It is a commonly used anticancer agent in animal systems. In this study, we provide ...evidence to show that NCS also acts as an agent in inducing programmed cell death (PCD) in tobacco Bright Yellow‐2 (TBY‐2) cell cultures. NCS treatment induces typical PCD‐associated morphological and biochemical changes, namely cell shrinkage, chromatin condensation and nuclear DNA degradation. To investigate possible signaling events, we analyzed the production of reactive oxygen species (ROS) and the function of mitochondria during PCD induced by NCS. A biphasic behavior burst of hydrogen peroxide (H2O2) was detected in TBY‐2 cells treated with NCS, and mitochondrial transmembrane potential (MTP) loss occurred after a slight increase. Pre‐incubation with antioxidant catalase (CAT) and N‐acetyl‐l‐cysteine (NAC) not only significantly decreased the H2O2 production but also effectively retarded the decrease of MTP and reduced the percentage of cells undergoing PCD after NCS treatment. In conclusion, our results suggest that NCS induces PCD in plant cells; the oxidative stress (accumulation of H2O2) and the MTP loss play important roles during NCS‐induced PCD.
Large blood pressure variability (BPV) will not only harm the target organ but also increase the possibility of the cardiovascular events. Since the damage of vascular system always leads to the ...alteration of the carotid wall, the structure and function of the carotid artery have been extensively examined in previous studies. In this work we conduct a study (60 subjects, aged 33–79) to evaluate the relationship between BPV and carotid intima-media thickness (IMT) in Shenzhen, which is one large city in the southern area of China. In our study, the blood pressure (BP) was collected using the 24 h ambulatory BP monitoring, and the BPV was evaluated using standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) during 24 h, daytime and nighttime. All the IMT measurements are collected by ultrasound. The results show that both the daytime, and 24 h systolic BPV evaluated by three indices are positively associated with IMT. Among them, daytime systolic BPV evaluated with ARV is the best variable to represent the increasing of carotid IMT. In addition, after adjusting by age, sex, smoking, hypertension, and mean BP and PP values, 24 h diastolic BPV evaluated with SD also presents the favorable performance.
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