Dietary supplementation with dried plum (DP) has been shown to reverse bone loss in osteopenic animals, but our understanding as to how bone metabolism is altered remains unclear. To address this issue, 6‐month‐old female Sprague Dawley rats (n=84) were either sham‐operated or ovariectomized (OVX) and assigned to: Sham‐ control diet (AIN‐93M), OVX‐control diet, OVX‐5% (w/w) DP, OVX‐15% DP, OVX‐25% DP or the positive control OVX+PTH (80 μg/kg/d x 5 days/wk). Post‐operatively, rats were maintained on control diet (6 wks) until osteopenia was confirmed, followed by 6 wks of treatment. DP (15% and 25%) improved vertebral bone density (p<0.05) compared to the OVX group, but did not restore bone density to that of the sham group. μCT analyses of the vertebral body demonstrated that trabecular bone volume, number, thickness were decreased (p<0.05) by OVX, and DP enhanced these structural properties. Finite element analysis revealed partial restoration of bone strength and stiffness by DP. All doses of DP decreased the OVX‐induced increase in bone turnover based on serum PINP and the 15% and 25% reduced bone resorption. In contrast, PTH maintained the increase in bone turnover and resorption associated with OVX. These data suggest that DP's effects on bone are mediated by slowing bone turnover and further studies should investigate how these effects are mediated. (Supported by USDA Grant #2006‐35200‐17383)
Objective The β,β‐carotene‐9′,10′‐oxygenase2 (BCO2) is a mitochondrial inner membrane protein broadly presented in mammals. It was initially discovered as an enzyme that catalyzes the asymmetric cleavage of carotenoids. Recently we have found that BCO2 knockout (KO) mice are more prone to obesity and diabetes. Therefore, the aim of this study was to investigate the mechanism by which BCO2 regulates lipid and glucose metabolism in human primary hepatocytes in culture and in BCO2 KO mice. Methods Human primary hepatocytes, HepG2 cells, and BCO2 knockout mice were used as experimental models. Quantitative real time PCR and Western blot were used for gene expression analysis. Untargeted metabolomics, the tolerance tests of glucose, insulin and pyruvate, and blood metabolic profiling were also performed. Results The results showed the declined expression of BCO2 protein in primary hepatocyte cultures exposed to high palmitate and/or glucose challenges. BCO2 protein expression was significantly suppressed in HepG2 cells, compared to the human primary hepatocytes. Over‐expression of human BCO2 attenuated lipid accumulation and intracellular oxidative stress in HepG2 cells. Deficiency of BCO2 caused higher mitochondrial respiratory activities, mitochondrial stress, systemic inflammation, elevation of non‐esterified fatty acids and fasting blood glucose, and glucose intolerance in young adult mice. Moreover, depletion of BCO2 resulted in enhanced de novo lipogenesis and gluconeogenesis, and accumulation of diacylglycerol in the liver tissues. However, the whole body fat content and the uptake of circulating lipids and glucose by muscles and/or white adipose tissues were not changed or even decreased in KO mice. Conclusions Collectively, the functional and metabolic data suggested that BCO2 contributes to normal mitochondrial function. Loss of BCO2 leads to mitochondrial dysfunction, oxidative stress, and subsequent metabolic disorders in mice.
Phenolic compounds found in grapes such as resveratrol have been shown to act as antioxidants which can scavenge free radicals and delay or prevent cancer development. Although there have been several studies that have investigated the anti‐cancer properties of resveratrol and grape seed extract, to our knowledge there is no study conducted on Rubaiyat, an Oklahoma red grape variety. The Rubaiyat grape variety was chosen due to its relatively high polyphenol content. We hypothesize that the polyphenols in Rubaiyat possess anti‐proliferative and anti‐apoptotic properties similar to that of resveratrol. MCF‐7 cells were treated with varying concentrations of Rubaiyat grape extract and resveratrol. The anti‐proliferative and anti‐apoptotic effects of grape extract and resveratrol were measured by the sulforhodamine B (SRB) and DAPI assays, respectively. Similar to resveratrol, Rubaiyat grape extract inhibited cell proliferation and induced apoptosis in human MCF‐7 breast cancer cells. However, higher concentrations of the extract were needed to inhibit cell proliferation and induce apoptosis in this cell line. The anti‐carcinogenic property of the Rubaiyat grape extract may be attributed in part to its effects on the apoptotic genes Bcl‐2 and Bax. (Supported by Oklahoma Agriculture Experiment Station)
Iron deficiency remains the most common micronutrient deficiency in the US. Diminished erythropoiesis and hemoglobin production as a result of iron deficiency are associated with impaired oxygen transport. Iron homeostasis is maintained through the action of Iron Regulatory Proteins (IRPs) which modulate the stability or translation of mRNAs encoding proteins of iron metabolism. Other mRNAs not intimately involved in cellular iron metabolism have also been described as targets of IRPs. One target, EPAS1, encodes an oxygen-sensitive transcription factor involved in the maintenance of cellular oxygen homeostasis. The focus of the current study was to examine the extent to which iron status contributes to the translational regulation of EPAS1 mRNA. Using a weanling rat model of iron deficiency, we assessed translational regulation of IRP target mRNAs in the liver by determining the polysomal distribution of target mRNAs. Approximately 50% of EPAS1 mRNA was located in a repressed pool of mRNA in response to iron deficiency. Similarly, ~86% of L-Ferritin mRNA, a canonical target of IRP, was located in a repressed pool in iron deficient animals. Our results suggest a role for IRPs in regulating EPAS1 translation in response to iron status and provide evidence for coordination of iron and oxygen sensing in response to a dietary iron deficiency. This work was supported by a grant from USDA/CSREES 2008-35200-04445 (SLC). Grant Funding Source: USDA/CSREES 2008-35200-04445
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)