Biochemical Mechanism of Gallium on Prevention of Fatal Cage-Layer Osteoporosis

The possible biochemical mechanism of gallium was studied in this paper. One-day-old hens were fed to up to 68 weeks on a control diet and diets containing gallium. Serum calcium and phosphorus, serum alkaline phosphatase, tartrate resistant acid phosphatase (TRAP), serum osteocalcin, homocysteine, C-terminal crosslinked telopeptides of collagen type I, and bone mineral content were measured, respectively. The beneficial effects of gallium supplementation on improvement of cage layer osteoporosis were attributable mainly to decrease TRAP activity, C-terminal crosslinked telopeptides of collagen type I level, plasma calcium and phosphate concentrations, and increase the mineral content in the bones and osteocalcin level in plasma.     

Leptin treatment prevents type I diabetic marrow adiposity but not bone loss in mice

Leptin is a hormone secreted by adipocytes that is implicated in the regulation of bone density. Serum leptin levels are decreased in rodent models of type 1 (T1-) diabetes and in diabetic patients. Whether leptin mediates diabetic bone changes is unclear. Therefore, we treated control and T1-diabetic mice with chronic (28 days) subcutaneous infusion of leptin or saline to elucidate the therapeutic potential of leptin for diabetic osteoporosis. Leptin prevented the increase of marrow adipocytes and the increased aP2 expression that we observed in vehicle-treated diabetic mice. However, leptin did not prevent T1-diabetic decreases in trabecular bone volume fraction or bone mineral density in tibia or vertebrae. Consistent with this finding, markers of bone formation (osteocalcin RNA and serum levels) in diabetic mice were not restored to normal levels with leptin treatment. Interestingly, markers of bone resorption (TRAP5 RNA and serum levels) were decreased in diabetic mice by leptin treatment. In summary, we have demonstrated a link between low leptin levels in T1-diabetes and marrow adiposity. However, leptin treatment alone was not successful in preventing bone loss.     

Effects of Feed Supplementation on Mineral Composition,Mechanical Properties and Structure in Femurs of Iberian Red Deer Hinds (Cervus elaphus hispanicus)

Few studies in wild animals have assessed changes in mineral profile in long bones and their implications for mechanical properties. We examined the effect of two diets differing in mineral content on the composition and mechanical properties of femora from two groups each with 13 free-ranging red deer hinds. Contents of Ca, P, Mg, K, Na, S, Cu, Fe, Mn, Se, Zn, B and Sr, Young’s modulus of elasticity (E), bending strength and work of fracture were assessed in the proximal part of the diaphysis (PD) and the mid-diaphysis (MD). Whole body measures were also recorded on the hinds. Compared to animals on control diets, those on supplemented diets increased live weight by 6.5 kg and their kidney fat index (KFI), but not carcass weight, body or organ size, femur size or cortical thickness. Supplemental feeding increased Mn content of bone by 23%, Cu by 9% and Zn by 6%. These differences showed a mean fourfold greater content of these minerals in supplemental diet, whereas femora did not reflect a 5.4 times greater content of major minerals (Na and P) in the diet. Lower content of B and Sr in supplemented diet also reduced femur B by 14% and Sr by 5%. There was a subtle effect of diet only on E and none on other mechanical properties. Thus, greater availability of microminerals but not major minerals in the diet is reflected in bone composition even before marked body effects, bone macro-structure or its mechanical properties are affected.     

Propranolol,a β-adrenergic antagonist,attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice

We investigated the effects of high calorie and low calorie diets on skeletal integrity, and whether β-adrenergic blockade (BB) attenuates bone loss induced by dietary calorie alteration. Male 6-week-old C57BL/6 mice were assigned to either an ad-lib fed control diet (CON), a high calorie diet (HIGH), or a low calorie diet (LOW) group. In each diet group, mice were treated with either vehicle (VEH) or propranolol, a β-adrenergic antagonist. Over 12-weeks, β-blockade mitigated body weight and fat mass increases induced by the high calorie diet. Femoral trabecular bone mineral density and the expression levels of osteogenic marker genes in bone marrow cells were reduced in HIGHVEH and LOWVEH mice, and BB significantly attenuated this decline only in HIGH mice. In summary, the magnitude of bone loss induced by low calorie diet was greater than that caused by high calorie diet in growing mice, and β-blockade mitigated high calorie diet-induced bone loss. [BMB Reports 2014; 47(9): 506-511]     

The effects of fatty acid composition on cardiac hypertrophy and function in mouse models of diet-induced obesity

High-fat diets (HFDs) are used frequently to study the development of cardiac dysfunction in animal models of obesity and diabetes. However, impairment in systolic function, often reported as declining ejection fraction, may not consistently occur in a given time frame which could be contributable to a variety of factors within the experimental design. One major factor may be the amounts of saturated and unsaturated fatty acids (FAs) that are present in the diet. To determine whether the FA content and composition were critical determinants in the development of cardiac dysfunction in response to high-fat feeding, we fed adult, male mice Western diet (45% fat, 60% saturated), Surwit diet (60% fat, 90% saturated), milk-fat-based diet (60% fat, 60% saturated) or high-fat Western diet (HFWD, 60% fat, 32% saturated) for 12 weeks. We report that neither the amount of total fat nor the ratio of saturated to unsaturated FAs in the diets differentially affects body weight and adiposity in mice. In addition, no evidence of systolic dysfunction is present after 12 weeks. Interestingly, the HFWD, with equal parts saturated, monounsaturated and polyunsaturated FAs, induces mild cardiac hypertrophy and diastolic dysfunction after 12 weeks, which coincides with elevated serum levels of arachidonic acid. Our results suggest that the dietary FA content and composition may be a primary determinant of diastolic, but not systolic, dysfunction in animal models of diet-induced obesity.     

A multi-mineral natural product inhibits liver tumor formation in C57BL/6 mice

C57BL/6 mice were maintained for up to 18 months on high-fat and low-fat diets with or without a multi-mineral supplement derived from the skeletal remains of the red marine algae Lithothamnion calcareum. Numerous grossly observable liver masses were visible in animals on the "western-style" high-fat diet sacrificed at 12 and 18 months. The majority of the masses were in male mice (20 out of 100 males versus 3 out of 100 females; p = 0.0002). There were more liver masses in animals on the high-fat diet than on the low-fat diet (15 out of 50 on high-fat versus 5 out of 50 on low-fat; p = 0.0254). The multi-mineral supplement reduced the number of liver masses in mice on both diets (3 out of 25 male mice in the low-fat diet group without the supplement versus 1 out of 25 mice with supplement; 12 of 25 male mice in the high-fat diet group without the supplement versus 3 of 25 mice with supplement [p = 0.0129]). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas), and 18 pre-neoplastic lesions. Out of eight hepatocellular carcinomas, seven were found in unsupplemented diet groups. Steatosis was widely observed in livers with and without grossly observable masses, but the multi-mineral supplement had no effect on the incidence of steatosis or its severity. Taken together, these findings suggest that a multi-mineral-rich natural product can protect mice against neoplastic and pre-neoplastic proliferative liver lesions that may develop in the face of steatosis.     

Using minimal supplements of trace minerals as a method of reducing trace mineral content of poultry manure

Experiments were conducted with broilers and layers with the aim of reducing manure content of zinc, copper and manganese by using lower supplemented levels of mineral proteinates. Broilers were fed maize-soy diets containing conventional levels of trace minerals provided by inorganic salts. Other treatments involved use of mineral proteinates fed at from 70–20% of the control diet levels. Diet generally had no effect (P>0.05) on body weight or feed efficiency to 42 d. A total collection procedure showed that at the lowest level of mineral proteinate supplementation excretion of zinc, manganese and copper was reduced by 38%, 52% and 21%, respectively. In a second study, layers were fed either conventional sources and levels of trace minerals, no trace minerals, or 20% of regular levels as mineral proteinates. Diet had no effect on egg numbers from 38–70 weeks. Egg size was always reduced in birds fed diets devoid of supplemental trace minerals. Using the lower levels of diet minerals, there was a 66% reduction in excretion of zinc and 78% reduction in excretion of manganese. It seems as though we are overfeeding trace minerals, and that with judicious use of mineral proteinates, it is possible to maintain performance while concomitantly reducing mineral content of manure.     

Ascorbic acid and other chelating agents in the trace-mineral nutrition of the aphid Myzus persicae on artificial diets

Growth of the aphidMyzus persicae fed artificial diets in which the required trace minerals (Fe, Cu, Mn, and Zn) were incorporated as chlorides was compared to growth on diets in which the minerals were supplied as sodium EDTA complexes. If the mineral chlorides were allowed to interact with L ascorbic acid prior to their incorporation into a diet, much less ascorbic acid was needed than if the ascorbic acid was added after incorporation of the mineral chlorides into a diet. Low levels of D ascorbic acid or citric acid acted similarly to L ascorbic acid. This was presumably by chelating the minerals. The complexes thus formed not only maintained the minerals in solution for ingestion but appeared to facilitate their utilization by the aphids. However, higher levels of L ascorbic acid were needed by the insects, presumably for purposes other than trace-mineral nutrition, when they were maintained for longer periods on the diets.     

Mineral supplementation of white wheat flour is necessary to maintain adequate mineral status and bone characteristics in rats

This experiment was designed to compare the effect of ingestion of a wheat flours on mineral status and bone characteristics in rats. White flour was tested either without further mineral supplementation or with Mg, Fe, Zn and Cu supplementation. The flour diets were compared to a control purified diet. Four groups of 10 male Wistar rats each were fed one of the experimental diets for 6 wk and mineral status and tissue retention as well as bone characteristics were determined. As expected, mineral intake, except for calcium, was significantly lesser in rats fed the white flour diet than in the other groups. The rats fed the white flour diet had the lowest food intake, weight gain, fecal excretion and intestinal fermentation. The most important result was that Mg and Fe status were drastically lower in rats fed the white flour diet than in those fed whole flour or control diets. The status of these both elements were significantly improved by the mineral supplementation of white flour. There were no major significant differences between mineral-supplemented white flour and whole flour groups in mineral status. Furthermore, bone mineral densities (total, metaphyseal and diphyseal) were significantly lower in rats fed white flour diet compared to the other diet groups, while no significant difference was observed between the mineral-supplemented white flour, whole flour or control diet groups. In conclusion, the present work shows clearly the importance of mineral-supplementation of white wheat flour to sustain an adequate intake of minerals. Our results indicate also that the whole wheat flour did not negatively alter mineral bioavailability, in comparison to mineral supplemented white flour. Clinical studies are still needed to confirm these rat results in human.     

Effect of Dietary Garcinia cambogia Extract on Serum Essential Minerals (Calcium, Phosphorus, Magnesium) and Trace Elements (Iron, Copper, Zinc) in Rats Fed with High-Lipid Diet

The aim of the study was to investigate the effect of Garcinia cambogia extract on serum calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe), zinc (Zn) and copper (Cu) concentrations in rats fed with the normal or the high-lipid and -cholesterol diet. Thirty 1-year-old female Sprague-Dawley rats (pathogen-free), weighing an average of 229 g, were randomly assigned to three experimental groups of ten animals each. Diets and tap water were given ad libitum for 75 days. Group 1 (control group) was fed with basal diet (2 % liquid vegetable oil, 0 % cholesterol), while the diets of groups 2 and 3 contained vegetable oil (2 % liquid vegetable oil and 5 % hydrogenated vegetable oil) and cholesterol (3 %) in high levels. 4,5 % G. cambogia extract containing 65 % HCA was added to the diet of group 3 as from day 45. Blood samples were withdrawn on days 0, 45 and 75. Serum mineral levels were analyzed using standard enzymatic colorimetric methods with a spectrophotometer. All significant differences were p<0.05. Serum Ca levels were not significantly different between all groups on days 45 and 75. Serum P level was significantly higher in the group fed with high-lipid diet and G. cambogia extract than in the control group on day 45. Serum Mg level was significantly higher in group 2 than in the control group on day 45. Serum Fe levels were significantly lower in the control group than in the other groups on days 45 and 75. Serum Zn level of the group fed with high-lipid diet and G. cambogia extract was significantly higher than in the control group on day 75. Serum Cu levels were significantly higher in group 2 than in the control group, and in group 3 than in group 2 on day 75. In conclusion, a diet containing the high fat amounts may lead to the increase in circular levels of some minerals due to the short-chain fatty acid production lowering the luminal pH which increases mineral solubility, or serving as a fuel for mucosal cells and stimulating cell proliferation in the large intestine. G. cambogia extract may be used in the P and Cu deficiencies due to increases resulting in the present P and Cu amounts in G. cambogia extract, or the use of phytate P in diet. It was hoped that with further evidence-based study this product will enter to mainstream medicines.     

Evaluation of the preventive effect of isoflavone extract on bone loss in ovariectomized rats

To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). OVX treatments reduced femoral and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased uterine weight (p<0.01), accelerated body weight increases (p<0.05), and increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone prevented the losses of bone density and mineral content caused by OVX (p<0.01). Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17beta-estradiol on the serum ALP and TRAP, body weight increase, and uterine weight change. We concluded that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.     

Avoiding Toxic Levels of Essential Minerals: A Forgotten Factor in Deer Diet Preferences

Ungulates select diets with high energy, protein, and sodium contents. However, it is scarcely known the influence of essential minerals other than Na in diet preferences. Moreover, almost no information is available about the possible influence of toxic levels of essential minerals on avoidance of certain plant species. The aim of this research was to test the relative importance of mineral content of plants in diet selection by red deer (Cervus elaphus) in an annual basis. We determined mineral, protein and ash content in 35 common Mediterranean plant species (the most common ones in the study area). These plant species were previously classified as preferred and non-preferred. We found that deer preferred plants with low contents of Ca, Mg, K, P, S, Cu, Sr and Zn. The model obtained was greatly accurate identifying the preferred plant species (91.3% of correct assignments). After a detailed analysis of these minerals (considering deficiencies and toxicity levels both in preferred and non-preferred plants) we suggest that the avoidance of excessive sulphur in diet (i.e., selection for plants with low sulphur content) seems to override the maximization for other nutrients. Low sulphur content seems to be a forgotten factor with certain relevance for explaining diet selection in deer. Recent studies in livestock support this conclusion, which is highlighted here for the first time in diet selection by a wild large herbivore. Our results suggest that future studies should also take into account the toxicity levels of minerals as potential drivers of preferences.     

Effects of dietary phytase on body weight gain, body composition and bone strength in growing rats fed a low-zinc diet

Phytic acid, a major phosphorous storage compound found in foodstuffs, is known to form insoluble complexes with nutritionally essential minerals, including zinc (Zn). Phytases are enzymes that catalyze the removal of these minerals from phytic acid, improving their bioavailability. The objective of the present study was to determine the ability of dietary phytase to affect body weight, body composition, and bone strength in growing rats fed a high phytic acid, low Zn diet. Rats (n = 20) were fed either a control (AIN-93) or phytase supplemented (Natuphos, BASF, 1,500 phytase units (FTU)/kg) diet for a period of 8 weeks. Phytase supplementation resulted in increased (P<.05) bone and plasma Zn, but no change in plasma inorganic phosphorous or bone levels of Ca, Fe, or Mg. The addition of phytase to the diets resulted in a 22.4% increase (P<.05) in body weight at the end of the study as compared with rats fed a control diet. Dual x-ray absorptiometry (DXA) revealed that phytase supplementation resulted in increase lean body mass (LBM, P<.001) and increased bone mineral content (BMC, P<.001) as compared with feeding the control diet. Bone studies indicated that femurs and tibias from phytase supplemented rats had greater mass (P<.05) and were stronger (P<.05) than rats fed the control diet. This data suggest that the addition of phytase to low Zn diets results in improved Zn status, which may be responsible for beneficial effects on growth, body composition, and bone strength.     

Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice

Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6–12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups–exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases structural strength after 8 weeks, making bones best able to resist fracture.     

Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice,which is further aggravated by supplementation of heme

The Western diet, rich in fat and red meat, predisposes for inflammatory bowel disease (IBD); however, little is known about mechanisms involved. Red meat contains high levels of heme, a well-known inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1). Pharmacological induction of HO-1 ameliorates experimental colitis. We analyzed the effect of a westernized high-fat (HF) diet supplemented with heme on intestinal HO-1 expression and dextran sulfate sodium (DSS)-induced colitis.Mice were fed chow or HF diets for 2 weeks. In the second week, the HF diet was supplemented with or without 0.5 μmol/g heme. Subsequently, the 3 diet groups were given drinking water with or without 4% DSS to induce colitis.Significant body weight reduction was first observed after 4 days in the chow/DSS mice (?5±3%), whereas this was evident already after 2 days (?6±2%) in HF/DSS mice, showing increased weight loss compared to chow/DSS mice in the following days. Heme supplementation further aggravated DSS-induced weight loss in HF mice (?18±4% vs. ?7±5% for HF+heme/DSS vs. HF/DSS, P<.01). Heme increased HO-1 expression in the colon epithelium but decreased villin messenger RNA levels, indicating epithelial damage. In contrast, heme did not affect DSS-induced colon shortening and histological scores of epithelial damage and inflammation.A westernized diet accelerates DSS-induced weight loss in mice, which is further aggravated by heme, despite the induction of HO-1 in the colon epithelium. Our data warrant a detailed analysis of the association of (red) meat-containing diets and the development of IBD.     

t10c12-CLA maintains higher bone mineral density during aging by modulating osteoclastogenesis and bone marrow adiposity

Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Earlier, we showed that CLA (equal mixture of c9t11-CLA and t10c12-CLA) could protect age-associated bone loss by modulating inflammatory markers and osteoclastogenesis. Since, c9t11-CLA and t10c12-CLA isomers differentially regulate functional parameters and gene expression in different cell types, we examined the efficacy of individual CLA isomers against age-associated bone loss using 12 months old C57BL/6 female mice fed for 6 months with 10% corn oil (CO), 9.5% CO + 0.5% c9t11-CLA, 9.5% CO + 0.5% t10c12-CLA or 9.5% CO + 0.25% c9t11-CLA + 0.25% t10c12-CLA. Mice fed a t10c12-CLA diet maintained a significantly higher bone mineral density (BMD) in femoral, tibial and lumbar regions than those fed CO and c9t11-CLA diets as measured by dual-energy-X-ray absorptiometry (DXA). The increased BMD was accompanied by a decreased production of osteoclastogenic factors, that is, RANKL, TRAP5b, TNF-alpha and IL-6 in serum. Moreover, a significant reduction of high fat diet-induced bone marrow adiposity was observed in t10c12-CLA fed mice as compared to that of CO and c9t11-CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections. In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t10c12-CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c9t11-CLA and linoleic acid treated cultures. In conclusion, these findings suggest that t10c12-CLA is the most potent CLA isomer and it exerts its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity.     

Effects of Exposure to Dietary Chromium on Tissue Mineral Contents in Rats Fed Diets with Fiber

This study evaluated the effects of diets with fiber (cellulose and/or pectin) supplemented with chromium(III) on homeostasis of selected minerals in femurs, thigh muscles, livers, and kidneys of rats. For 6 weeks, male rats were fed experimental diets: a fiber-free diet (FF), a diet containing 5 % cellulose (CEL), 5 % pectin (PEC), or 2.5 % cellulose and 2.5 % pectin (CEL?+?PEC). These diets had 2.53 or 0.164 mg Cr/kg diet. The tissue levels of Ca, Mg, Zn, Fe, and Cr were determined by using atomic absorption spectrometry. Supplementing diets with Cr resulted in significantly higher Cr levels in the femurs of rats fed the CEL diet and significantly higher Cr and Fe levels in the rats fed the CEL?+?PEC diet compared to the rats fed FF diet. Muscle Ca content was significantly lower in the rats fed the CEL?+?PEC?+?Cr diet compared to the rats fed FF?+?Cr diet. The rats consuming the PEC?+?Cr diet had the highest liver Cr content. The highest kidney Zn content was observed in the rats fed diets containing Cr and one type of fiber. These results indicate that diets containing chromium at elevated dose and fiber have a significant effect on the mineral balance in rat tissues.     

Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet.

Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.     

Bone inflammation and altered gene expression with type I diabetes early onset

Type I diabetes is associated with bone loss and marrow adiposity. To identify early events involved in the etiology of diabetic bone loss, diabetes was induced in mice by multiple low dose streptozotocin injections. Serum markers of bone metabolism and inflammation as well as tibial gene expression were examined between 1 and 17 days post‐injection (dpi). At 3 dpi, when blood glucose levels were significantly elevated, body, fat pad and muscle mass were decreased. Serum markers of bone resorption and formation significantly decreased at 5 dpi in diabetic mice and remained suppressed throughout the time course. An osteoclast gene, TRAP5 mRNA, was suppressed at early and late time points. Suppression of osteogenic genes (runx2 and osteocalcin) and induction of adipogenic genes (PPARγ2 and aP2) were evident as early as 5 dpi. These changes were associated with an elevation of serum cytokines, but more importantly we observed an increase in the expression of cytokines in bone, supporting the idea that bone, itself, exhibits an inflammatory response during diabetes induction. This inflammation could in turn contribute to diabetic bone pathology. IFN‐γ (one of the key cytokines elevated in bone and known to be involved in bone regulation) deficiency did not prevent diabetic bone pathology. Taken together, our findings indicate that bone becomes inflamed with the onset of T1‐diabetes and during this time bone phenotype markers become altered. However, inhibition of one cytokine, IFN‐γ was not sufficient to prevent the rapid bone phenotype changes. J. Cell. Physiol. 218: 575–583, 2009. © 2008 Wiley‐Liss, Inc.     

Analyses of African elephant (Loxodonta africana) diet with various browse and pellet inclusion levels

To more closely simulate the diet of free-ranging elephants, the diet of six (2.4) African elephants (Loxodonta africana) was altered to include more browse and less pelleted complete feed (5% total diet). Dietary proximate compounds, minerals, vitamins A (and carotenoids), D and E, and fatty acids were analyzed on pelleted diet items and forages including hay, grass, and browse. A total of 42 browse species were offered over 1 year with an average total diet inclusion of 5.2% (dry matter basis) per day. Dietary Na and Se were low while Fe and Mn were high compared to published intake levels for elephants. Analyzed nutrients within browse varied widely among seasons and species. Ingredient analyses were used to create predicted elephant nutrient intake for (a) the current diet, (b) a diet excluding pellets, and (c) a diet excluding pellets and providing browse at doubled levels. Formulated diets excluding pellets had lower mineral levels than the current diet and doubled browse did not alter mineral inclusions of concern. This study provides seasonal data on the nutrient levels of Southeastern browse species important for various pachyderm and herbivorous species. Predicted nutrient intake with new diet scenarios does not support the exclusion of pellets in the diets of African elephants without greater browse quantity availability, strict diet management, or additional supplements.