Coordination of Iron and Oxygen Signaling Through Post-Transcriptional Regulation of Hypoxia Inducible Factor-2Alpha

Department of Nutritional Science

Оценка надежности высоконадежных систем с учетом ЗИП

Предложены приближенные верхние и нижние оценки коэффициента готовности высоконадежной восстанавливаемой системы со структурной избыточностью. Полученные расчетные соотношения могут использоваться для оценки надежности высоконадежных систем с учетом различных стратегий пополнения ЗИП

Comparisons of the iron deficient metabolic response in rats fed either an AIN-76 or AIN-93 based diet

Abstract Background Previous studies examining the metabolic consequences of dietary iron deficiency have reported elevated serum glucose concentrations in iron-deficient animals. Importantly, the majority of these findings were observed using an earlier version of a laboratory animal diet (AIN-76A) in which the primary carbohydrate source was sucrose – a disaccharide known to negatively impact both glucose and lipid homeostasis. The AIN-76A diet formula was improved in 1993 (AIN-93) to optimize animal nutrition with a major change being the substitution of cornstarch for sucrose. Therefore, we sought to examine the effects of iron deficiency on steady-state glucose homeostasis and the hepatic expression of glucose- and lipid-related genes in rats fed an iron-deficient diet based on either an AIN-76A or AIN-93 diet. Methods The study design consisted of 6 treatment groups: control (C; 40 mg Fe/kg diet), iron deficient (ID; ≤ 3 mg Fe/kg diet), or pair-fed (PF; 40 mg Fe/kg) fed either an AIN-76A or AIN-93 diet for 21 d. Hemoglobin and hematocrit were measured in whole blood. Serum insulin and cortisol were measure by ELISA. Serum glucose and triacylglycerols were measured by standard colorimetric enzyme assays. Alterations in hepatic gene expression were determined by real-time qPCR. Results Hemoglobin and hematocrit were significantly reduced in both ID groups compared to the C and PF groups. Similarly, animals in the both ID groups exhibited elevated steady-state levels of blood glucose and insulin, and significantly decreased levels of circulating cortisol compared to their respective PF controls. Serum triacyglycerols were only increased in ID animals consuming the AIN-76A diet. Hepatic gene expression analyses revealed a ~4- and 3-fold increase in the expression of glucokinase and pyruvate dehydrogenase kinase-4 mRNA, respectively, in the ID group on either diet compared to their respective PF counterparts. In contrast, the expression of lipogenic genes was significantly elevated in the AIN-76 ID group, while expression of these genes was unaffected by iron status in the AIN-93 ID group. Conclusions These results indicate that an impaired iron status is sufficient to alter glucose homeostasis, though alterations in lipid metabolism associated with ID are only observed in animals receiving the AIN-76A diet.</p

A Comparative Study of the Metabolic and Skeletal Response of C57BL/6J and C57BL/6N Mice in a Diet-Induced Model of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) represents a complex clinical scenario of altered energy metabolism and increased fracture incidence. The C57BL/6 mouse model of diet-induced obesity has been used to study the mechanisms by which altered glucose homeostasis affects bone mass and quality, but genetic variations in substrains of C57BL/6 may have confounded data interpretation. This study investigated the long-term metabolic and skeletal consequences of two commonly used C57BL/6 substrains to a high fat (HF) diet. Male C57BL/6J, C57BL/6N, and the negative control strain, C3H/HeJ, mice were fed a control or HF diet for 24 wks. C57BL/6N mice on a HF diet demonstrated an increase in plasma insulin and blood glucose as early as 4 wk, whereas these responses were delayed in the C57BL/6J mice. The C57BL/6N mice exhibited more severe hepatic steatosis and inflammation. Only the C57BL/6N mice lost significant trabecular bone in response to the high fat diet. The C3H/HeJ mice were protected from bone loss. The data show that C57BL/6J and C57BL/6N mice differ in their metabolic and skeletal response when fed a HF diet. These substrain differences should be considered when designing experiments and are likely to have implications on data interpretation and reproducibility

qRT-PCR Analyses of Genes Involved in Osteoclastogenesis and Osteoblast Activity.

<p>Bone marrow (A) was analyzed for relative mRNA abundance of the osteoclastgensis gene nuclear factor of activated T-cells (<i>Nfatc1</i>), while the flushed femur (B-D) was used to assess genes involved in osteoblast activity and function: alkaline phosphatase (<i>Alp</i>), type 1 collagen (<i>Col1a1</i>), and osteocalcin (<i>Ocn</i>) in sham-operated (Sham) and ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango. Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p

Histological Images of the Tibia and µCT Analyses of Trabecular Bone Volume in the Vertebra and Tibia.

<p>Representative images of the proximal tibia are shown with H&E stain following the 8 week treatment period (A). Comparisons of trabecular bone morphometric parameters in sham-operated (Sham) and osteopenic ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango. Trabecular bone microarchitectural of (B) bone volume/total volume (BV/TV) in the vertebral body (□) and proximal tibia (▪). Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p

Percent Change in Vertebral Trabecular Bone Normalized to OVX-Control at Baseline.

<p>Percent change in vertebral BV/TV in ovariectomized (OVX) mice fed control diet, or control diet supplemented with either 25% (w/w) dried plum, apple, apricot, grape, or mango relative to baseline OVX controls. The percent change was calculated by determining the difference between the OVX group mean BV/TV at baseline and BV/TV of individual animals at the final time point, and then expressing that value relative to baseline. Bars represent the mean ± SE, <i>n</i>  =  6 mice in each group. Bars that share the same superscript letter are not significantly different from each other (<i>p<</i>0.05).</p