Biomedical subjects

J F Aloia

Publications and source records attributed to J F Aloia.

At least 19 recordsLinked to original sources

PubMed1999

Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat.

The aim of the present study was to examine cancellous bone changes induced by exercise on three different skeletal sites, the lumbar vertebra, the proximal, and the distal tibia, in the young growing rat. Forty 4-week-old female Sprague-Dawley rats were randomized into 4 groups of 10 animals each; 8 weeks exercise (8EX), 8 weeks sedentary control (8CON), 12 weeks exercise (12EX), and 12 weeks sedentary control (12CON). The exercise regimen consisted of treadmill running at 24 m/min 1 hr per day 5 days a week. After each period of exercise, the proximal and distal tibial metaphyses (PTM and DTM, respectively) and the fifth lumbar (L5) vertebral body were processed for histomorphometry of the cancellous bone (secondary spongiosa) and cortical periosteum. Eight and twelve weeks of exercise significantly increased the mineral apposition rate and bone formation rate in the PTM and DTM, and 12 weeks of exercise significantly increased the labeled perimeter in the DTM, compared with the age-matched controls. Eight and twelve weeks of exercise significantly increased cancellous bone volume in the PTM (mean +/- standard deviation, 8EX; 19.1 +/- 2.9% vs 8CON; 14.3 +/- 3.1%, P < 0.05 and 12EX; 18.8 +/- 3.5% vs 12CON; 15.2 +/- 3.3%, P < 0.05), and 12 weeks exercise significantly increased cancellous bone volume in the DTM, compared with age-matched control (12EX; 32.5 +/- 7.7%, 12CON; 22.2 +/- 4.8%, P < 0.05). The increase in cancellous bone volume by 12 weeks exercise was higher in the DTM than that in the PTM (43.4% and 24.0%, respectively). On the other hand, the exercise did not significantly affect cancellous bone volume and bone formation in the L5 vertebral body, although the cortical periosteal bone formation rate and the L5 vertebral bone mass were increased. These findings suggest that cancellous bone adaptation to treadmill exercise is site specific, and the effect may be influenced by factors such as mechanical loading and metaphyseal bone architecture in the young growing rat.

Adaptation, Physiological↗

PubMed1999

Effect of hypophysectomy on the proliferation and differentiation of rat bone marrow stromal cells.

Conditions such as estrogen deficiency, skeletal unloading, and aging have all been demonstrated to have various effects on the proliferation and differentiation of bone marrow stroma-derived osteoprogenitor cells. Here we have sought to examine the effects of pituitary hormone deficiency on the proliferation and the differentiation of these osteoprogenitor cells using the hypophysectomized (HX) rat as a model. In the present study, we use an in vitro culture system to examine the effects of HX on the osteogenic potential of rat bone marrow stroma. With the intact animal as a control, we used [3H]thymidine incorporation and cell number as indexes of proliferation. We also measured alkaline phosphatase enzyme activity, relative levels of osteocalcin expression with RT-PCR, and osteopontin and bone sialoprotein steady-state levels by Northern blot to delineate the effect on differentiation. Our results indicate that osteoprogenitor cells exposed to a pituitary hormone-deficient environment in vivo demonstrate an enhanced proliferative capacity and also exhibit an augmented expression of differentiation markers when exposed to an optimal environment in vitro.

Animals↗

PubMed1998

Discordance between ultrasound of the calcaneus and bone mineral density in black and white women.

Black women have 40% of the incidence rate for hip fracture and have a higher bone mineral density (BMD) than white women. The possibility was raised that bone quality may be disproportionately greater than the advantage in bone density in protection against osteoporotic fractures in black versus white women. Ultrasound (US) of the calcaneus is believed to measure properties of bone in addition to its density. We performed bone density measurements and US of the calcaneus in 108 black and 177 healthy white women, aged 20-70 years. The highest correlation was seen between total body bone density and speed of sound (r = 0.75). The interracial differences in BMD were all statistically significant and varied from 3.4 to 7.6%. The US measurements had lesser interracial differences than the bone density measurements, with velocity barely different between races. These findings suggest that US of the calcaneus measures properties of bone different from density. Fracture prediction data using US from prospective data in white women should not be extrapolated to black women because of the discordance between bone density and US measurements. Prospective studies are needed comparing US measurements in black women to the occurrence of osteoporotic fractures.

Adult↗

PubMed1998

Anabolic effect of prostaglandin E2 in bone is not dependent on pituitary hormones in rats.

Prostaglandin E2 (PGE2) is an anabolic agent of bone in vivo but the mechanism of its action still remains unclear. The aim of this study was to determine whether the effect of PGE2 on skeleton is mediated by pituitary hormones. Forty female, Sprague-Dawley rats were divided into four groups: baseline control (basal), age-matched intact control (CON), hypophysectomy (HX), and HX + PGE2 (2 mg/kg/day) with 10 animals in each group. The basal group was sacrificed at 2 months of age, and the remaining groups after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double fluorescent-labeled 40 micron-thick sections of the proximal tibia and tibial shaft. Our results show that HX resulted in a cessation of bone growth, a decrease in cancellous bone volume, and cortical bone gain compared with the age-matched, intact CON rats. Compared with the HX group, the HX + PGE2 group had a significantly greater tibial bone density (mean +/- SE, HX + PGE2:1.595 +/- 0.007 versus HX:1.545 +/- 0.013), percent cancellous bone volume (21.4 +/- 2.0 versus 8.41 +/- 1.70), percent cortical bone area (87.2 +/- 0.85 versus 81.7 +/- 0.7), and ratio of cortical area to marrow area (7.14 +/- 0.56 versus 4.52 +/- 0.21). Increased bone masses by PGE2 in the HX animals were accompanied by an increase in the trabecular and endosteal-labeled surface and bone formation rate. The trabecular number and width were increased whereas trabecular separation was decreased in the HX + PGE2 group compared with the HX group (P < 0.05). PGE2 treatment also caused a decrease in the tibial endosteal eroded surface and medullar cavity of the HX animals. In conclusion, this study clearly demonstrates that PGE2 (2 mg/kg/day) in the HX rats increases both cortical and cancellous bones and improves trabecular architecture in the tibia after 6 weeks of treatment. These skeletal alterations are due to a stimulation of bone formation and a suppression of bone resorption activity. These findings suggest that the anabolic effect of PGE2 in bone is independent of pituitary hormones.

Animals↗

PubMed1998

Biochemical and hormonal variables in black and white women matched for age and weight.

Weight and age may influence the levels of indexes of bone remodeling and the calciotropic hormones. In a study of interracial differences in these women, our black population was heavier than our white population. We therefore matched a subset of 96 black and 96 white women from our larger population for age and weight to determine whether a racial difference exists independent of the effects of weight and age. In addition, we were able to measure other indexes of bone remodeling (N-telopeptide of cross-linked collagen and pyridinoline cross-links), as well as hormones that may influence calcium metabolism (insulin-like growth factor-1 (IGF-1), insulin, calcitonin, and gastrin) in this subset. All indexes of bone remodeling were lower in black women. Black postmenopausal women had lower serum levels of calcidiol and higher parathyroid hormone (PTH) levels. The higher bone mass of black women is associated with lower bone remodeling in the presence of skeletal resistance to PTH. Serum IGF- 1, insulin, and calcitonin levels did not differ significantly between races. Serum gastrin levels were higher in black women. The higher levels of gastrin in black women should be investigated further for its possible effect on the absorption of calcium salts.

Adult↗

PubMed1998

Relationship of body water compartments to age, race, and fat-free mass.

Water compartments were studied in 72 black and 128 white women, aged 20 to 70 years. Total body water (TBW) was measured by tritiated water dilution, and extracellular water (ECW) was measured by using delayed gamma neutron activation for the determination of total body chloride. Intracellular water (ICW) was assessed as the difference between TBW and ECW. Fat-free mass (FFM) was estimated by the measurement of total body potassium (TBK) and total body fat (TBF) by measurement of total body carbon (TBC). Total body protein was calculated from total body nitrogen (TBN). TBW was found to decline with age and to also be significantly influenced by body size. The extracellular water space was 41.5% of TBW. The decline of TBW with age is due primarily to a decline in ICW. The hydration of the FFM increased with age for the overall population because of a decline in TBK and TBN and an increase in ECW. Body composition models that have assumed constancy of hydration should be adjusted not only for gender but for age and body size.

Adipose Tissue↗

PubMed1997

Histologic evidence: growth hormone completely prevents reduction in cortical bone gain and partially prevents cancellous osteopenia in the tibia of hypophysectomized rats.

BACKGROUND: In previous studies we found that the cause of bone loss in young hypophysectomized (HX) animals was due primarily to an inhibition in growth-dependent bone gain and a decrease in bone turnover. The aim of this study was to determine whether growth hormone, which has stimulatory effects on bone growth and turnover, can prevent HX-induced skeletal alterations in rats. METHODS: Female Sprague-Dawley rats were divided into baseline control (BASAL), age-matched control (CON), HX, HX plus low-dose GH (1.5 mg/kg/d, subcutaneously), and HX plus high-dose GH (4.5 mg/kg/d) groups. The BASAL group was sacrificed at 2 months of age and the remaining groups were sacrificed after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double-fluorescent-labeled 40 microm-thick sections of the proximal tibia and tibial shaft. RESULTS: Both low- and high-dose GH prevented the HX-induced decrease of IGF-I serum levels. High-dose GH also significantly increased the body weight and the wet weight of the gastrocnemius muscle when compared to the CON groups. In the tibial shaft, the periosteal labeled surface, mineral apposition rate and bone formation rate were higher in both of the GH-treated groups than in the HX group (P < 0.05). The tissue area and cortical bone area of the high-dose GH-treated rats were greater than those of the HX rats, but did not differ from those of the CON rats. In the proximal tibia, both low- and high-dose GH prevented an HX-induced decrease in the longitudinal growth rate and growth plate width, and increased surface-based bone formation compared to the HX and CON. Cancellous bone volume, tissue-based bone formation rate, and eroded surface in both of the GH-treated groups were higher than those of the HX group, but lower than those of the BASAL and CON groups (P < 0.05). Bone architecture of the HX rats was also improved after GH treatment. CONCLUSIONS: This study clearly demonstrates that GH replacement at the dosage of 4.5 mg/kg/d can completely prevent the HX-induced reduction in cortical bone gain in the tibial shaft, but can only partially prevent cancellous osteopenia in the proximal tibia after six weeks.

Animals↗

PubMed1997

Comparison of body composition in black and white premenopausal women.

We examined 23 pairs of black and white premenopausal women to determine whether there were ethnic differences in body composition. The pairs were matched on weight and height. Each woman had measurements of total body water taken by a tritiated water dilution technique, total body nitrogen, and total body carbon by neutron-activation, mineral ash by dual x-ray absorptiometry, and body potassium by whole body counting. Differences between blacks and whites were compared with the use of both the two-compartment and four-compartment models. The two-compartment model showed that in premenopausal black and white women of similar age, heights, and weights, blacks had significantly more lean mass. The four-compartment model resulted in similar conclusions. The black women had larger protein, mineral, and water compartments and less fat than whites. It may be that body weight measurements as an indicator of obesity should be adjusted for black versus white women.

Absorptiometry, Photon↗

PubMed1997

Effects of 17 beta-estradiol administration on cortical and cancellous bone of ovariectomized rats with and without hypophysectomy.

Pituitary hormones are essential for bone growth and bone turnover. Hypophysectomy (HX) diminishes mitogenesis and abolishes the high bone turnover rate induced by ovariectomy (OV). It is not known whether the suppressive effect of estrogen on bone resorption is diminished or abolished by HX. The present study investigates the effects of 17 beta-estradiol (E2) (20 micrograms/wk) on cortical and cancellous bone mass and bone turnover as measured by histomorphometry in HX + OV (HO) rats. Sprague-Dawley rats at 2 months of age were OV or HO and the experiment was performed over a 6 week period. Hypophysectomy + OV (HO) resulted in a cessation of periosteal bone formation, and longitudinal bone growth and a decrease in cancellous bone volume. The tibial dry weight and tibial density were significantly lower in the HO than in the intact or OV groups. Administration of E2 to HO rats partially prevented cancellous bone loss, whereas the same dosage of E2 fully prevented cancellous bone loss in rats with OV alone. Nevertheless, cancellous bone volume was higher in the HO + E2 than in the HO-alone groups. Estradiol administration in HO rats did not suppress cancellous bone formation rate or the eroded surface as much as it did in the OV rats. The suppressive effect of E2 on periosteal bone formation rate and mineral apposition rate was also diminished in HO rats. However, factorial ANOVA showed that the effects of E2 on increasing cancellous bone volume and decreasing periosteal bone formation rate and mineral apposition rate were still significant in the HO rats. Tibial dry weight and tibial density did not differ between HO and HO + E2 groups. In conclusion, we have demonstrated that the estrogen-induced effects of preventing cancellous bone loss, of suppressing bone formation, and resorption as seen in OV rats was diminished but not abolished in HO rats.

Animals↗

PubMed1997

Effects of estrogen and growth hormone on skeleton in the ovariectomized rat with hypophysectomy.

To investigate whether growth hormone (GH) and 17beta-estradiol (E2) replacement can prevent osteopenia induced by pituitary and ovarian hormone deficiency [by hypophysectomy and ovariectomy (HX+OV)], we administered relatively low doses of GH (2.3 IU x kg(-1) x day(-1)) and E2 (100 microg x kg(-1) x wk(-1)) in experiment 1 and relatively high doses of GH (13.5 IU x kg(-1) x day(-1)) and E2 (3,500 microg x kg(-1) x wk(-1)) in experiment 2 to 2-mo-old HX+OV Sprague-Dawley rats for 6 wk. Our data show that the HX+OV of rats results in diminished periosteal bone formation, longitudinal bone growth, and decreased cancellous bone volume. Administration of either the low or high dose of GH to these rats increased their systemic growth, serum levels of osteocalcin, and cortical bone formation. Either low or high doses of GH or E2 alone only partially prevent cancellous bone loss. However, the combined treatment of GH plus E2 resulted in an additive increase in the cancellous bone mass. We conclude that the additive effect of GH plus E2 on cancellous bone is attributed to the suppressive effect of E2 on bone resorption and the anabolic effect of GH on bone formation.

Animals↗

PubMed1997

Sodium distribution in black and white women.

Delayed gamma neutron activation analysis (DGNA) was performed on 99 black and 168 healthy white women, aged 20-80 years, to examine sodium distribution in the two ethnic groups. Elements measured included total body levels of sodium (TBNa) and chlorine (TBCl). The black women were heavier, and consequently had a higher body surface area. Sodium excess (Naes) was calculated from TBNa and TBCl. Total body water was measured by tritiated water dilution. TBNa was higher in black than white women, and this difference persisted when the values were corrected for body surface area. TBNa and Naes declined significantly with age in white women, whereas extracellular fluid sodium (ECFNa) remained constant. The change with age was not statistically significant in black women for TBNa, Naes or ECFNa. Our sample of healthy black women had a higher TBNa and Naes than healthy white women. This difference persisted after adjustment for body surface area, so that values for sodium distribution need to be adjusted for race. The change in TBNa with age in white women appears to be due to their decline of skeletal tissue mass with a consequent decline in nonexchangeable sodium.

Adult↗

PubMed1996

Risk for osteoporosis in black women.

Models of involutional bone loss and strategies for the prevention of osteoporosis have been developed for white women. Black women have higher bone densities than white women, but as the black population ages there will be an increasingly higher population of black women with osteoporosis. Strategies should be developed to reduce the risk of black women for fragility fractures. Dual energy X-ray absorptiometry measurements of the total body, femur, spine, and radius were performed on 503 healthy black and white women aged 20-80 years. Indices of bone turnover, the calcitrophic hormones, and radioisotope calcium absorption efficiency were also measured to compare the mechanisms of bone loss.The black women had higher BMD values at every site tested than the white women throughout the adult life cycle. Black women have a higher peak bone mass and a slightly slower rate of adult bone loss from the femur and spine, which are skeletal sites comprised predominantly of trabecular bone. Indices of bone turnover are lower in black women as are serum calcidiol levels and urinary calcium excretion. Serum calcitriol and parathyroid hormone levels are higher in black women and calcium absorption efficiency is the same in black and white women, but dietary calcium intake is lower in black women. Black and white women have a similar pattern of bone loss, with substantial bone loss from the femur and spine prior to menopause and an accelerated bone loss from the total skeleton and radius after menopause. The higher values for bone density in black women as compared with white women are caused by a higher peak bone mass and a slower rate of loss from skeletal sites comprised predominantly of trabecular bone. Low-risk strategies to enhance peak bone mass and to lower bone loss, such as calcium and vitamin D augmentation of the diet, should be examined for black women. The risk vs. benefits of hormonal replacement therapy should be determined, especially in older women.

Adult↗

PubMed1996

Racial differences in femoral dimensions and their relation to hip fracture.

White women have a higher rate of age-specific hip fractures than black women. Recently, femoral dimensions have been implicated in osteoporotic fractures. To study racial differences in femoral dimensions, dual X-ray absorptiometry scans were obtained for two similar groups of 50 white women and 50 black women. We measured the hip axis length (the distance from below the lateral aspect of the greater trochanter to the inner pelvic brim), the neck width and the neck/shaft angle on the scan print-out. The observer was masked to the race of the subject. The results were analyzed using the independent t-test and showed that the hip axis length and the neck width were significantly longer in the white women than in the black women (p values < 0.05 and < 0.02 respectively) but that the neck/shaft angle was not statistically different in the two groups. We conclude that femoral geometry differs among races. Whether this contributes to the lower risk of hip fracture in black women will require prospectively based studies.

Adult↗

PubMed1996

Differential effects of dietary calcium augmentation and hormone replacement therapy on bone turnover and serum levels of calcitrophic hormones.

The mechanism of action of retardation of postmenopausal bone loss may be different for dietary calcium augmentation and hormonal replacement therapy (HRT). We performed a three-arm, placebo-controlled, randomized clinical trial comparing an intake of calcium of 1700 mg with: (1) calcium augmentation with HRT and (2) placebo. One hundred and eighteen women entered the study; 17 patients dropped out of the study. The vast majority of women were less than 2 years postmenopause. Bone mineral density declined significantly in the placebo group. The previously reported rates of change in the HRT group were significantly positive for total body calcium and the trochanter and not significantly different from zero for the others. The rate of change in the calcium augmentation group was intermediate between that in the two other groups, and achieved statistical significance compared with placebo for the total body calcium measurement and for the neck of the femur. Measurements were made prior to treatment and at the end of the study (2.9 years +/- 1.1 SD) for parameters of bone turnover and the calcitrophic hormones, to examine whether the mechanism of action was different for calcium augmentation versus hormonal therapy. There were no changes in the placebo group. The calcium augmentation group had a significant increase in 24-h urinary calcium and declining values for urinary collagen cross-links (pyridinium and deoxypyridinium), urinary hydroxyproline and calcitriol. The group treated with HRT and dietary calcium augmentation also had an increase in urinary calcium and a decline in collagen cross-links and urinary hydroxyproline and skeletal alkaline phosphatase; serum calcitriol did not change. The HRT group also displayed a drop in serum osteocalcin, and an increase in nephrogenous cAMP. Serum parathyroid hormone remained unchanged in all groups. Dietary calcium augmentation retards postmenopausal bone loss by decreasing resorption. The addition of HRT results in a more marked decline in bone resorption parameters and a suppression of parameters of bone formation. Whereas calcium augmentation suppressed calcitriol levels, the addition of HRT resulted in maintenance of calcitriol levels, possibly through enhancement of the renal effects of parathyroid hormone, although other mechanisms are possible.

Bone Density↗

PubMed1996

Ovariectomy-induced high turnover in cortical bone is dependent on pituitary hormone in rats.

The aim of this study is to examine the interrelationship of pituitary and ovarian hormone deficiency on the regulation of bone growth and bone formation rate. 48 female rats, at 3 months of age, were divided into age-matched intact control, hypophysectomized (HX), ovariectomized (OV), and HX + OV groups. Ten rats were killed at 3 months of age as baseline controls, and the rest of the animals were killed 5 weeks after surgery. Serum levels of osteocalcin and dynamic histomorphometry on the periosteal surface of the tibial shaft and fifth lumbar vertebrae were measured to evaluate systemic and local bone turnover. Tibial and fourth lumbar vertebral bone area, bone mineral content, and bone density were measured by dual-energy X-ray absorptiometry (DXA). Our results confirmed that OV increased and HX suppressed systemic and periosteal bone formation parameters in both bone sites, OV increased and HX suppressed the gain in bone size and bone mass. When OV rats were HX, the serum levels of osteocalcin and periosteal bone formation parameters of the tibial shaft and the fifth lumbar vertebrae were, however, depressed and did not differ from that of the HX alone. DXA results show that the effect of OV on bone size and bone mass is also abolished by HX. In conclusion, we have demonstrated that OV increases tibial and lumbar vertebral bone formation and bone growth and this effect is pituitary hormone dependent.

Absorptiometry, Photon↗

PubMed1996

Aging in women--the four-compartment model of body composition.

The four-compartment model of body composition was examined in 155 white women through measurement of total body carbon (TBC), nitrogen (TBN), calcium (TBCa), and water levels. The age (mean +/- SD) of the population was 51.4 +/- 13.5 years, and values for the four compartments were as follows (in kilograms): protein 8.9 +/- 1.0, water 30.9 +/- 3.5, mineral 2.6 +/- 0.4, and fat 22.6 +/- 7.3. There was a linear change with age for protein and water, whereas mineral and fat were curvilinear. These latter two compartments also showed differences in premenopausal and postmenopausal rates of change. Various models were fit to the data to adjust for body size and age. Each of the four compartments (mineral, water, fat, and protein) changed with age, with fat increasing and the other compartments declining. The equation, y = age + age2 + height + weight, fit the data as well as the other models. Equations are provided to assess body composition in populations with disorders of nutrition, as well as other illnesses, using height, weight, and age as covariates. Since this was a cross-sectional study, longitudinal studies will have to be performed to confirm the accuracy of rates of change with age predicted with each compartment.

Absorptiometry, Photon↗

PubMed1996

Calibration of the delayed-gamma neutron activation facility.

The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99% of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1%. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards.

Body Composition↗

PubMed1996

Body composition in normal black women: the four-compartment model.

The four-compartment model of body composition was studied in 112 healthy black women to develop normative data to be used to assess deviations in illness. Each compartment was measured by an independent method: tritiated water dilution, prompt-gamma neutron activation analysis (for nitrogen), inelastic neutron scattering (for carbon) and dual energy x-ray absorptiometry (for calcium). The mean age of the population was 43.2 years. Race was self-declared. The mean values for the four compartments were [kg SE] protein: 9.6 (0.07); mineral 3.0 (0.03); fat 24.2 (0.70); and water 33.1 (0.29). Each of the compartments changed significantly with age (P < .0001). There were declines in total body water, mineral, and protein, whereas fat increased linearly with age. Linear regressions performed on pre- and postmenopausal women showed a significant difference only for the mineral compartment. Various models were fit to the data to adjust for body size and age. The equation y = age + height + weight fits the data as well as the other models. Equations and graphs were developed to assess each compartment using this linear model and may be used to assess the body composition status of healthy and ill black women. Although black women tended to be heavier than white women, after controlling for differences in body weight (and age) black women had a greater mass of protein, mineral, and water and a similar fat store. These differences, while statistically significant, were not of great magnitude. This was a cross-sectional study and suspected trends with aging must be confirmed by a longitudinal study.

Adipose Tissue↗