The relationship between aromatase activity and body fat distribution

The metabolism of androstenedione (A) to estrone (E1) and 5 alpha-reduced androgens was studied in stromal cells derived from human adipose tissue from different body sites. The tissue was obtained from non-obese patients undergoing cosmetic liposuction or at the time of surgery for reduction mammoplasty. The conversion of A to E1 per 1x 10(6) cells was between 6- and 30-fold greater in the upper thigh, buttock, and flank than in the abdomen. These differences were present in primary culture and persisted to at least the third subculture. Estrogen formation in breast adipose tissue was similar to that found in cells from abdominal fat. The formation of 5 alpha-reduced metabolites (5 alpha-androstenedione, androsterone, and dihydrotestosterone) varied from patient to patient but was similar in cells from different body sites. These studies show that the regional distribution of fat may influence the metabolism of androgens in adipose tissue, with upper body fat tending to form a lower ratio of estrogens to 5 alpha-reduced androgens than lower body fat.     

Omental and subcutaneous adipose tissue steroid levels in obese men

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.     

Free anterolateral thigh flap for extremity reconstruction: clinical experience and functional assessment of donor site

From August of 1995 through July of 1998, 38 free anterolateral thigh flaps were transferred to reconstruct soft-tissue defects. The overall success rate was 97 percent. Among 38 anterolateral thigh flaps, four were elevated as cutaneous flaps based on the septocutaneous perforators. The other 34 were harvested as myocutaneous flaps including a cuff of vastus lateralis muscle (15 to 40 cm3), either because of bulk requirements (33 cases) or because of the absence of a septocutaneous perforator (one case). However, vastus lateralis muscle is the largest compartment of the quadriceps, which is the prime extensor of the knee. Losing a portion of the vastus lateralis muscle may affect knee stability. Objective functional assessments of the donor sites were performed at least 6 months postoperatively in 20 patients who had a cuff of vastus lateralis muscle incorporated as part of the myocutaneous flap; assessments were made using a kinetic communicator machine. The isometric power test of the ratios of quadriceps muscle at 30 and 60 degrees of flexion between donor and normal thighs revealed no significant difference (p > 0.05). The isokinetic peak torque ratio of the quadriceps and hamstring muscles, including concentric and eccentric contraction tests, showed no significant difference (p > 0.05), except the concentric contraction test of the quadriceps muscle, which revealed mild weakness of the donor thigh (p < 0.05). In summary, the functional impairment of the donor thighs was minimal after free anterolateral thigh myocutaneous flap transfer.     

The development of adipocytes in primary stromal-vascular culture of fetal pig adipose tissue

Primary cultures of stromal-vascular cells of adipose tissue from fetuses at 70 and 110 days of gestation were evaluated as potential model systems for studies of fetal adipocyte differentiation and proliferation. In the cultures, fat cells developed as very discrete clusters. Fat cell cluster development was dependent on initial cell density and time. Histochemical analysis for NADP-dependent dehydrogenases revealed an age of donor effect. Similar levels of enzymes (malate and glucose-6-phosphate dehydrogenase) were apparent in fat cell clusters and stromal cells in cultures of cells from fetuses at 70 days of gestation. These enzymes were only present in fat cell clusters in cultures of cells from fetuses at 110 days of gestation. The distribution of histochemically detectable esterase activity was dependent on the cell density at time of analysis. In areas of high cell density, esterase was restricted to fat cell clusters whereas, both stromal cells and fat cells were esterase reactive in areas of low cell density. Omitting PMS from the dehydrogenase media revealed differences in enzyme reactions of cells grown on collagen-coated and uncoated glass surfaces. These studies demonstrate that primary cultures of stromal-vascular cells from 110-day-old fetuses would be a useful system to identify factors involved in adipocyte proliferation and differentiation.     

The effect of interleukin-8 on the viability of injected adipose tissue in nude mice

Adipose tissue injection as a free graft for the correction of soft-tissue defects is a widespread procedure in plastic surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study was to improve the viability of the injected fat by the use of interleukin-8. The rationale for the use of interleukin-8 was its abilities to accelerate angiogenesis and attract inflammatory cells and fibroblasts, providing the injected adipocytes more feeding vessels and a well-established graft bed to enhance their viability. Human adipose tissue, obtained by suction-assisted lipectomy, was re-injected into the subcutis in the scalp of nude mice. Interleukin-8 (0.25 ng) was injected subcutaneously to the scalp as a preparation of the recipient site 24 hours before the fat injection and was added to the fat graft itself (25 ng per 1 cc of injected fat). In the control group, pure fat without interleukin-8 was injected and no interleukin-8 was added for the preparation of the recipient site. One cubic centimeter of fat was injected in each animal in both the study and control groups. There were 10 animals in each group. The animals were euthanized 15 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. In addition, triglyceride content and adipose cell sizes were measured as parameters for fat cells viability. Histologic analysis demonstrated significantly less cyst formation in the group treated with interleukin-8. No significant differences were found between the groups with regard to graft weight and volume or the other histologic parameters investigated. No significant differences were demonstrated in adipose cell sizes and their triglyceride content. In conclusion, less cyst formation, indicating improved quality of the injected fat, can be obtained by the addition of interleukin-8. Further studies of various dosages of interleukin-8 and their long-term effect are required before these encouraging results could be applied clinically.     

Sex differences in abdominal, gluteal, and thigh LPL activity

Lipoprotein lipase (LPL) activity is necessary for adipocytes to take up triglycerides from the circulation, and regional differences in LPL activity could help determine regional fat storage. LPL activity has been reported to increase as a function of fat cell size, but this issue has not been extensively evaluated in different depots comparing sexes. Our objective was to determine whether sex alters the relationship between LPL activity and fat cell size. Subcutaneous adipose tissue biopsies were taken from the abdomen and thigh after an overnight fast and 1 h after a meal in 65 females (BMI 25.4 +/- 0.8, means +/- SE) and 41 males (BMI 23.7 +/- 0.3); gluteal adipose samples were obtained in 47 of the females and 27 of the males. Fat cell size was greater in females than males in thigh (P < 0.005) and gluteal (P < 0.05) regions but not in the abdomen. There was a relationship between fasting LPL activity/fat cell and fat cell size in females (abdomen r2 = 0.52, P < 0.0001; gluteal r2 = 0.23, P < 0.005; thigh r2 = 0.19, P < 0.005). In males, this relationship was seen only in the abdomen (r2 = 0.51, P < 0.0001) and thigh (r2 = 0.17, P < 0.05). Males and females had a significantly different relationship in the thigh only in the fasted state. Similar results were found in the fed state, although the strength of the relationship decreased in the abdominal regions for females only. This suggests fundamental differences in the regulation of triglyceride uptake between males and females and adipose regions.     

The effect of hyperbaric oxygenation on the viability of human fat injected into nude mice

Autologous free-fat injection for the correction of soft-tissue defects has become a common procedure in plastic surgery. The main shortcoming of this method for achieving permanent soft-tissue augmentation is the partial absorption of the injected fat, an occurrence that leads to the need for both overcorrection and repeated fat reinjection. Improving the oxygenation of the injected fat has been suggested as a means of helping to overcome the initial critical phase that occurs postinjection (when the fat cells are nourished by osmosis), increasing phagocyte activity, accelerating fibroblast activity and collagen formation, and enhancing angiogenesis. In addition, the hyperbaric oxygen-mediated decrement in endothelial leukocyte adhesion will decrease cytokine release, thereby reducing edema and inflammatory responses. The purpose of the present study was to examine the effect of hyperbaric oxygenation on improving the viability of injected fat. Adipose tissue obtained from human breasts by suction-assisted lipectomy was injected into the subcuticular nuchal region in nude mice. The mice were then exposed to daily hyperbaric oxygen treatments, breathing 100% oxygen at 2 atmospheres absolute (ATA) for 90 minutes. The duration of the administered hyperbaric oxygen therapy was 5, 10, or 15 days, according to the study group. Mice exposed to normobaric air alone served as the control group, and each group included 10 animals. The rats were killed 15 weeks after fat injection. The grafts were dissected out, weight and volume were measured, and histologic evaluation was performed. In all of the study groups, at least part of the injected fat survived, giving the desired clinical outcome. No significant differences could be found between the groups regarding fat weight and volume. Histopathologic examination of the dissected grafts demonstrated a significantly better integrity of the fat tissue in the group that received hyperbaric oxygen for 5 days (p = 0.047). This finding was manifested by the presence of well-organized, intact fat cells, along with a normal appearance of the fibrous septa and blood vessels. The worst results were found in animals treated by hyperbaric oxygenation for 15 consecutive days. An inverse correlation was found between an increased dose of the high-pressure oxygen and fat tissue integrity (r = -0.87, p = 0.076). The toxic effects of highly reactive oxygen species on fat cells might explain the failure of an excessively high dose of hyperbaric oxygen to provide any beneficial outcome. The clinical relevance of these results should be further investigated.     

Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice

Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity.     

Thigh tissue composition exhibits a curvilinear relationship with aging: A cross-sectional study

Objectives:To explore whether quadratic model will better estimate the relationship between aging and thigh tissue composition in a cohort that range in age from young to older adults.Methods:51 healthy subjects participated in this investigation. All subjects underwent CT imaging for the thigh. Cross-sectional area of the fat and muscular tissues in the thigh were quantified. Hierarchical regression models were created. Age was entered first into the models to estimate its linear relationship with the thigh tissues. Then the squared value of the age variable was entered second to identify whether a quadratic model would better estimate the relationship between the variables.Results:The linear model was significant for thigh muscular tissue. Quadratic models were able to account for additional significant prediction of the cross-sectional area of thigh tissues. Muscular area decreased with aging until 60 years after that it didn’t change. Fat areas increased with aging until 45-50 years and then it decreased.Conclusions:The cross-sectional area of different thigh tissues exhibit a curvilinear pattern with aging. Muscular tissue area may not change after 60 years; this could be explained by the reduction in fat that may infiltrate inside the muscles and offset the muscular reduction.     

Minimally invasive harvest of the gracilis muscle.

Acceptance of minimally invasive plastic surgery has been predicated on decreasing morbidity while maintaining the quality and costs of outcomes. The major patient complaint about the gracilis muscle donor site has almost solely been related to the length of the thigh scar, and thus would appear to be an ideal indication for outcome improvement using minimally invasive techniques. A method of endoscopically assisted gracilis muscle harvest, therefore, was developed, starting with a transverse incision just proximal to the knee to identify the gracilis tendon. This endoscopic port allows retrograde subfascial dissection of the muscle and precise identification of its anatomic course, whereupon a small proximal medial thigh incision can be made secondarily for direct access to the vascular pedicle. This variation has now been used successfully in 10 patients. The mean proximal thigh scar length was 8.30 +/- 0.74 (SD) cm, and total surgical scars measured 11.84 +/- 0.95 cm, compared with 27.73 +/- 9.55 cm for 16 patients for whom an open method had been used. This diminished scar length was a statistically significant improvement (p < 0.05), verifying the value of the surgical endoscope as an adjunct for harvest of the gracilis muscle as a free flap.     

肥胖者脂肪组织中TNF-α表达与脂肪细胞大小的相关性分析

目的探讨肥胖者网膜脂肪和皮下脂肪两处肿瘤坏死因子-α(TNF-α)蛋白的表达与脂肪细胞大小的相关性。方法选取正常体重者16名,中心型肥胖者32名拟行外科手术患者,术中取出网膜脂肪和皮下脂肪标本,测定脂肪细胞大小,采用western blot方法测定TNF-α蛋白表达。结果肥胖者网膜脂肪和皮下脂肪两处TNF-α蛋白的水平均比正常体重对照组表达高(P<0.01),肥胖者网膜脂肪组织TNF-α蛋白表达高于皮下脂肪(P<0.05),同时研究发现肥胖者皮下脂肪细胞和网膜脂肪细胞大小均明显大于正常体重组(P<0.05),且肥胖者网膜脂肪和皮下脂肪两处脂肪组织TNF-α蛋白表达与脂肪细胞大小呈正相关(网膜:r=0.808,P<0.01;皮下:r=0.452,P<0.05)。结论肥胖者网膜脂肪和皮下脂肪细胞增大,在肥胖相关胰岛素抵抗的发生中起到了重要的作用。     

Apoptosis in extracorporeal preserved inguinal fat flaps of the rat

Fat cells are fragile cells with a short life span outside the body. Ways to reduce cell death in a biochemical way are almost unknown due to scarce information on the type of cellular death that is induced in fat tissue. This study was designed to investigate the apoptotic pathways of fat tissue in a permanent perfusion bioreactor system with the Hannover preservation solution and the Eurocollins solution in fat flaps of rats. In Lewis rats, the inguinal adipofascial flaps were elevated bilaterally and placed in a bioreactor at 37°C. To detect caspases 3, 8, 9 and 12, immunofluorescence stains of fat tissue specimen were analysed at several time points after preservation of flaps were placed in Hannover solution and Eurocollins solution for 10 days. An additional visual assessment of viability by a calcein based life/dead test was performed. It revealed a superior viability of the adipose tissue preserved in Hannover solution. Immunofluorescence staining demonstrated that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors were activated, as Caspases 8, 9 and 12 were detected. Caspase 3 as an effector in the common apoptotic pathway was detected as well. Adipose tissue preserved at 37°C ex vivo in a bioreactor system undergoes apoptosis. Immunofluorescence examination of the fat tissue preserved ex vivo revealed that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors are being activated. Significantly less activation of Caspase 3, 8, 9 and 12 in flaps preserved in Hannover solution in comparison to Eurocollins was found, supporting the anti apoptotic characteristics of Hannover solution. Based on these findings, further research to modify the apoptotic pathways to ameliorate viability of fat tissue can be performed.     

Cloning and Expression of SFRP5 in Tibetan Chicken and its Relationship with IMF Deposition

Secreted frizzled related protein 5 (SFRP5), an anti-inflammatory adipokine, is relevant to the adipocyte differentiation. In order to clarify its role in regulating intramuscular fat (IMF) deposition in Tibetan chicken, the full-length sequence of the Tibetan chicken SFRP5 gene was cloned. The relative expression of SFRP5 gene was detected using quantitative RT-PCR in various tissues of 154 days old Tibetan chicken, as well as in breast muscle, thigh muscle, and adipose tissue at different growth stages. The results showed that SFRP5 gene was expressed in all examined tissues but highly enriched in adipose tissue. Temporal expression profile showed that the expression of SFRP5 was gradually decreased in breast muscle, but was fluctuated in thigh muscle and adipose tissue with the growth of Tibetan chicken. Furthermore, correlation analysis demonstrated that the expression of SFRP5 in breast muscle, thigh muscle and adipose tissue was correlated with IMF content at different levels. The results indicated that Tibetan chicken SFRP5 is involved in IMF deposition.     

脂肪细胞的分化及调控

越来越多的研究结果表明脂肪组织不仅仅是被动的能量储存器官 ,而且是能够分泌多种激素类物质的内分泌器官 ;脂肪细胞分化及其调控失常与人类多种疾病如肥胖症、糖尿病、脂肪肝、高脂血症及乳腺癌等密切相关。对脂肪细胞分化机制及其调控的研究 ,不但对于探讨上述重大生命和疾病过程具有重要理论意义 ,而且对于上述疾病的预防与治疗 ,特别是对于在细胞和分子水平上筛选针对上述疾病的药物 ,也具有实际意义。本文从脂肪细胞的起源、前脂肪细胞向脂肪细胞的分化过程、脂肪细胞分化的调控 ,以及对脂肪细胞分化研究应注意的问题等进行了综述 ,以期对脂肪细胞分化及其调控进行全面总结     

Analysis of lipocyte viability after liposuction

Free fat grafts from liposuction aspirate can be used as donor material for soft-tissue augmentation. The purpose of this study was to attempt to identify a subpopulation of adipose cells within liposuction aspirate with the greatest viability and, it is hoped, a greater chance for increased survival after transplantation. Liposuction samples were obtained from 20 individuals (16 women, four men; age range, 27 to 49 years). These samples were then centrifuged at 50 g. At 2-minute intervals, specimens from three different areas (superficial, middle, deep) were obtained from each specimen. After collagenase degradation, the specimens were stained with trypan blue, and the number of viable cells were counted. The bottom (deepest) layer consistently contained the highest number of viable cells after centrifugation: 250 percent more viable cells when compared with the top layer (p < 0.0001) and 140 percent more viable cells when compared with the middle layer (p < 0.0002). Centrifugation beyond 2 minutes did not increase the number or proportion of viable adipocytes. When using aspirated fat from liposuction for soft-tissue augmentation, centrifugation for 2 minutes at 50 g will stratify the adipocytes, with more viable cells being found at the deepest layer. Using only this bottom portion of the fat layer for transplantation will yield a fat graft with a greater number of viable adipocytes, potentially improving fat graft survival and decreased fat graft resorption.     

Effect of radiation on skin expansion and skin flap viability in pigs

The aim of the present study was to investigate the effect of radiation treatment both on skin tissue expansion with the chronic inflation of subcutaneous expanders and on skin flap viability in surgically delayed and expanded skin in the pig. One flank in each of six pigs (initially weighing 17 +/- 1.8 kg) was randomly assigned for radiation treatment, and the contralateral flank served as a nonirradiated control. Three mirror-image, 8 x 10 cm, rectangular templates were marked on each flank; these templates were randomly assigned to the construction of a delayed skin flap (group A), a skin flap raised on expanded skin (group B), or a skin flap raised on expanded skin with a capsulectomy before flap surgery (group C). Radiation treatment was performed using sequential radiation with three fractions per week (810 cGy/fraction) for 2 weeks, with a total dose of 4,860 cGy. Twelve weeks after radiation treatment, skin expanders (8 x 10 cm) were installed subcutaneously in the locations assigned for skin expansion. Skin expansion by the inflation of subcutaneous skin expanders with saline twice weekly was started 8 weeks later and lasted for 3 weeks. Two weeks after surgical delay and the last skin expansion, 8 x 20 cm skin flaps were raised on the locations assigned for delayed skin flaps, expanded skin flaps, and expanded skin flaps with a capsulectomy. Skin flap viability was assessed 24 hours later using a fluorescein dye-staining technique. Skin expansion by the inflation of subcutaneous expanders with saline was slower (p < 0.05) in the radiated skin (39 +/- 6 ml/filling) than in the nonirradiated control skin (51 +/- 6 ml/filling). Radiation reduced the overall area of expanded skin by 23 percent (p < 0.05) compared with the control. Radiation treatment also reduced skin viability by 36 percent (p < 0.05) in the delayed skin flaps, 27 percent (p = 0.10) in the expanded skin flaps, and 36 percent (p < 0.05) in the expanded skin flaps with a capsulectomy when compared with their contralateral, nonirradiated controls. There were no significant differences in skin viability among these three types of skin flaps within the radiated and nonirradiated groups. Taken together, these observations indicate that radiation treatment reduced the effectiveness of the surgical delay procedure, the amount of subcutaneous skin expansion (by an increase in skin area), and skin flap viability. However, a capsulectomy alone did not affect the viability of skin flaps raised on expanded skin.     

An alternative method to minimize pain in the split-thickness skin graft donor site

In the art of plastic surgery, the reconstruction of tissue defects to obtain cosmetic and functional recovery is the major concern. Skin grafting is the most frequently used procedure for reconstructing defects of various size and anatomical localizations. On the other hand, donor-site problems associated with this invaluable procedure are inevitable. Various methods are used in the postoperative management of the partial-thickness donor site created during the harvest of a split-thickness skin graft. Each technique has the potential for complications of fluid loss, excessive pain, prolonged period of healing and immobilization, hypertrophic scarring, and undesirable pigmentation. Donor-site pain is probably the most disturbing complication in the early postoperative period. The aim of this article is to point out the significance of donor-site pain, which has not been emphasized thoroughly in the literature, and to introduce flap skin as a potential graft donor site for patients in whom reduction of donor-site morbidity is of primary concern. The principal goal of the technique described in this article is to eliminate donor-site pain by harvesting the graft from the flap that is insensate after the elevation. In 15 patients, the overlying skin of the flap that had been used for reconstructive purposes was used as the donor site (group I). In the remaining 23 patients, the posterolateral thigh was used as the donor site (group II). Donor-site discomfort was recorded during the first 8 days postoperatively using a visual analogue scale. To analyze the data, we used the Friedman test, Dunn's multiple comparison test, and Mann-Whitney U test. It was observed that the visual analogue scale of both of the groups showed a significant decrease within days (group I, p < 0.0001; group II, p < 0.0001). The mean pain scores were significantly lower in group I than in group II (p < 0.0001). When donor-site pain is of primary concern, this procedure provides uneventful and comfortable healing while avoiding postoperative pain in the donor site. For that reason, this technique might be used in appropriate cases to minimize donor-site pain.     

Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance

Both adipocyte hyperplasia and hypertrophy are determinant factors for adipocyte differentiation during the development of obesity. p21(WAF1/CIP1), a cyclin-dependent kinase inhibitor, is induced during adipocyte differentiation; however, its precise contribution to this process is unknown. Using both in vitro and in vivo systems, we show that p21 is crucial for maintaining adipocyte hypertrophy and obesity-induced insulin resistance. The absence of p21 in 3T3-L1 fibroblasts by RNA-mediated interference knockdown or in embryonic fibroblasts from p21(-/-) mice impaired adipocyte differentiation, resulting in smaller adipocytes. Despite normal adipose tissue mass on a normal diet, p21(-/-) mice fed high energy diets had reduced adipose tissue mass and adipocyte size accompanied by a marked improvement in insulin sensitivity. Knockdown of p21 in enlarged epididymal fat of diet-induced obese mice and also in fully differentiated 3T3-L1 adipocytes caused vigorous apoptosis by activating p53. Thus, p21 is involved in both adipocyte differentiation and in protecting hypertrophied adipocytes against apoptosis. Via both of these mechanisms, p21 promotes adipose tissue expansion during high fat diet feeding, leading to increased downstream pathophysiological consequences such as insulin resistance.     

Measuring leg muscle and fat mass in humans: comparison of CT and dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the random and systematic discrepancies between these two methods. Thigh skeletal muscle area (single-slice CT) was suboptimally (r(2) = 0.74, P < 0.0001) related to DEXA-measured thigh fat-free mass (FFM). In contrast, thigh muscle and adipose tissue volumes (multislice CT) were highly related to DEXA-measured thigh FFM and fat (both r(2) = 0.96, P < 0.0001). DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume, whereas multislice-CT-measured leg muscle mass was less (P < 0.0001) than DEXA-measured leg FFM. The systematic discrepancies between the two approaches were consistent with the 10-15% nonfat components of adipose tissue. In conclusion, CT and DEXA measures of appendicular soft tissue are highly related. Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques.     

Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells

Injection of aspirated fat for the correction of tissue defects is a common procedure in plastic surgery. The reported rates of fat cell survival vary greatly in the medical literature, and different techniques of harvesting, processing, and reinjecting the fat cells are claimed to be responsible for these differences. However, there is no agreement concerning the best way to process the harvested fat before reinjection. The present study was initiated to examine and evaluate the effect of a simple method of isolating the fat particles on the outcome of fat graft survival. In this study, the nude mouse model was used to examine the survival and take of the fat graft concentrated before injection by the cumbersome recommended closed centrifugation technique in comparison with the authors' recommended open method, using an operating room cotton towel as a platform for concentrating the fat cells and separating them from fluids, oil, and debris. One milliliter of concentrated human fat cells preprocessed by towel separation was injected into the nuchal subcutis of 11 nude mice in the study group, and the same amount of fat that was preprocessed by centrifugation was injected into 11 control mice. Injected fat survived in both groups. No significant differences were found regarding fat graft weight and volume, although a tendency for better survival was noticed in the experimental group. Histologic evaluation of the grafts revealed significantly less fibrosis within the study group, meaning that the quality of the fat grafts was better. The authors found this method to be simple, cheap, and friendly to the surgeon in comparison with traditional processing using the centrifuge.