311, No. A significant relationship was found between the ratio of initial to final modulus and the elastin/collagen ratio, which reached statistical significance in subcutaneous AT (r = 0.87, P = 0.025) but not in omental tissue, where the individual data points were more widely scattered. [25], Epicardial adipose tissue (EAT) is a particular form of visceral fat deposited around the heart and found to be a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function. 12, Osteoarthritis and Cartilage, Vol. Each adipocyte is closely encapsulated by an extracellular matrix that has been described as consisting of a basement membrane rich in type IV collagen surrounded by a matrix rich in fibrous collagens (4). Beige adipocytes take on a multilocular appearance (containing several lipid droplets) and increase expression of uncoupling protein 1 (UCP1). [72][73] Data from these studies suggest that environmental factors like diet and exercise may be important mediators of browning. The area of the energy dissipation density loop, a measurement of energy dissipation over the stretch-relaxation cycle, was also significantly lower in subcutaneous than omental AT paired samples (P = 0.006, n = 13; BMI 30.9 ± 6.3 kg/m2). 26, No. Decellularized adipose matrix has recently been the focus of preclinical characterization as a potential solution for soft-tissue defect filling. Different meters use various methods to determine the body fat to weight ratio. Connective tissue matrix includes fibers embedded in an amorphous GROUND SUBSTANCE. [61] β3 agonists, like CL316,243, have also been developed and tested in humans. discovered the protein leptin that the genetically obese mouse lacked. To control degradation and volume persistence, the scaffold was crosslinked using hexamethylene diisocyanate and 1-Ethyl-3-(-3-dimethylaminopropyl) carbodiimide. We also see the cells translate and reorientate with respect to one another within the field of view. The correlations between the initial and final moduli and the compositional data on individual specimens were investigated. 2018, 2 May 2017 | Journal of Biophotonics, Vol. The changes that occur in the hypothalamus to result in leptin resistance in obesity are currently the focus of obesity research. Using ChIP-seq in conjunction with other tools, recent studies have identified over 30 transcriptional and epigenetic factors that influence beige adipocyte development. Figure \(\PageIndex{3}\). 4, 27 June 2018 | Bioengineering, Vol. Participants were recruited at the preoperative appointment for laparoscopic bariatric surgery, and written informed consent was obtained. also used microarray analysis to demonstrate that insulin deficiency inhibits the differentiation of beige adipocytes but does not disturb their capacity for browning. Samples from bariatric surgery patients were taken with approval by the local research ethics committee (ref. 1G, the stress was relaxed over ∼50 min and followed a two-exponential course. See: List of Doctor Who universe creatures and aliens (0–9, A–G) § Adipose, "Role of pericytes in skeletal muscle regeneration and fat accumulation", "Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding", "Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice", "The Prevention and Treatment of Obesity", Fat on the Inside: Looking Thin is Not Enough, "Estimating visceral fat area by multifrequency bioelectrical impedance", "The perils of portliness: causes and consequences of visceral adiposity", "Molecular mechanisms of inflammation in obesity-linked insulin resistance", "Anthropometric Assessment of Neck Adipose Tissue and Airway Volume Using Multidetector Computed Tomography: An Imaging Approach and Association With Overall Mortality", "Anthropometrically predicted visceral adipose tissue and blood-based biomarkers: a cross-sectional analysis", "Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III)", "Waistline Worries: Turning Apples Back Into Pears", "Effect of exercise training intensity on abdominal visceral fat and body composition", "Influence of exercise intensity on abdominal fat and adiponectin in elderly adults", "A dose-response relation between aerobic exercise and visceral fat reduction: systematic review of clinical trials", "Mobilization of Visceral and Subcutaneous Adipose Tissue in Response to Energy Restriction and Exercise", "Human epicardial adipose tissue is a source of inflammatory mediators", "Abdominal subcutaneous adipose tissue: a protective fat depot? Nonparametric tests were used for data analysis. 1F and summarized in Table 4. Samples were mounted on paddles as described above and laid horizontally, completely immersed in PBS, pH 7.4, at room temperature. The hydrated dimensions of the specimen were measured using a micrometer prior to testing, and the specimen, ∼8–17 mm in length, 3–6.5 mm in width, and 1.5–3.5mm in thickness, was attached using a small quantity of high-viscosity superglue gel (Everbuild, Stick 2 Superglue Gel) that was applied to two metal paddles. It has been suggested that the inability to store dietary lipid in adipocytes could result in its deposition as ectopic fat around the heart, muscle, and liver, predisposing an individual to obesity-related health problems (3, 27, 39). In contrast with clinical tools, one relatively inexpensive type of body fat meter uses the principle of bioelectrical impedance analysis (BIA) in order to determine an individual's body fat percentage. [36][37][38] The exercise regulation of marrow fat suggests that it bears some physiologic similarity to other white adipose depots. Multiphoton imaging was consistent with previous light and electron microscopic studies that have drawn attention to the rich networks of collagen fibers in both the pericellular and interlobular matrices in AT (4, 5, 7, 17, 26, 29). *Both of these authors have contributed equally to this article. RNA sequencing (RNA-Seq) is a powerful computational tool that allows for the quantification of RNA expression for all genes within a sample. Its major role is the storage of surplus dietary triglycerides (37), and it expands with the development of obesity. 16, No. 306, No. 5, 9 March 2017 | Scientific Reports, Vol. A1 and A3 are the amplitudes of the 2 exponential components, A2 is the asymptote and r is the goodness-of-fit coefficient. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.[3]. This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor for cardiovascular disease (even in the absence of diabetes mellitus and hypertension). The energy dissipation density decreased slightly over five cycles, as found in many soft tissues (10). 21, No. 131, No. analyzed the data; N.A., J.M., E.G., A.C.S., K.K., and C.P.W. [5] Of all the depots in the mouse, the gonadal depots are the largest and the most easily dissected,[6] comprising about 30% of dissectible fat. 2C), the cells were almost completely space-filling with smooth outlines, which obscured the very fine pericellular matrix shown in Fig. [42], There is a constant flux of FFAs entering and leaving adipose tissue. A body fat meter is a widely available tool used to measure the percentage of fat in the human body. C and D: a subcutaneous AT sample studied at 0 and 30% strain, respectively. [94], Adipose tissue has a density of ~0.9 g/ml. When PBS was exchanged for deionized water while the tissue was held at 30% strain, there was a decrease in the force of 31 ± 9% (P = 0.005, n = 10) in omental and 31 ± 10% (P = 0.002, n = 12) in unpaired samples of subcutaneous AT. It is increasingly accepted that the capacity for expansion of AT with its storage capacity may not only modify the obesity phenotype but determine the amount of storage of surplus triglycerides as ectopic fat deposition and with it determine the risk of obesity-associated complications such as diabetes (18, 24, 30, 34). 54, No. A panniculus complicates surgery of the morbidly obese individual. 1, C–E. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. P < 0.05 was considered significant. Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 2). 1, Lymphatic Research and Biology, Vol. 17-18, 21 August 2020 | International Journal of Molecular Sciences, Vol. One such study used microarray analysis in conjunction with Ingenuity IPA software to look at changes in WAT and BAT gene expression when mice were exposed to temperatures of 28 and 6 °C. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. Fat cells have an important physiological role in maintaining triglyceride and free fatty acid levels, as well as determining insulin resistance. After an initial stress-strain measurement, the tissue was equilibrated at 30% strain and the PBS in the bath replaced by deionized water. We compared the mechanical properties of subcutaneous and omental fat. The dry weight of the residue was measured, and then it was placed under the multiphoton microscope. Four regulators of transcription are central to WAT browning and serve as targets for many of the molecules known to influence this process. At the end of this procedure, 8–10% (w/v) fibroin solution was obtained. 3, Tissue Engineering Part A, Vol. After the stress had reequilibrated, stress-strain and stress relaxation measurements were performed as described above. 10, 22 July 2016 | Scientific Reports, Vol. 2, 4 July 2018 | Aesthetic Surgery Journal, Vol. When leptin levels drop, the body interprets this as a loss of energy, and hunger increases. The sample was then immediately relaxed at the same rate, allowing the energy dissipation density from straining the tissue to 30% strain to be quantified from the area between the loading and relaxation curves. [26] Marked component differences have been observed in comparing EAT with subcutaneous fat, suggesting a depot specific impact of stored fatty acids on adipocyte function and metabolism. At strains of ≤30%, AT produced nonlinear stress-strain curves, as shown in Fig. Instead, the tissue deforms on a larger scale as a gap opens up between the two groups of cells within the image. 34, No. Measurements on these samples were compared with assessed intrasubject variability, and the mean values for the patient were used in subsequent analysis. It may remain as a literal "apron of skin" if a severely obese person quickly loses large amounts of fat (a common result of gastric bypass surgery). Using Finite Element Analysis and a Voronoi Polyhedron model, we manipulated the viscoelasticities of the core materials, shell thickness, porosity, and cell shape to achieve a broad range of composite properties. Here, we investigate cell-type heterogeneity in two population-level … An electron microscope study, Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus, Extracellular matrix 4: the elastic fiber, Sbarbati A, Accorsi D, Benati D, Marchetti L, Orsini G, Rigotti G, Panettiere P, Subcutaneous adipose tissue classification, Thematic review series: adipocyte biology. RNA-Seq has been used in both human and mouse studies in an attempt characterize beige adipocytes according to their gene expression profiles and to identify potential therapeutic molecules that may induce the beige phenotype. The microscopy system has been described in detail elsewhere (23). It is comprised of a heterogeneous collection of cell types that can differentially impact disease phenotypes. Apart from adipocytes, which comprise the highest percentage of cells within adipose tissue, other cell types are present, collectively termed stromal vascular fraction (SVF) of cells. [10] Visceral fat is composed of several adipose depots, including mesenteric, epididymal white adipose tissue (EWAT), and perirenal depots. These cells swell as they store fat and shrink when the fat is used for energy. Similarly, cartilage is another type of connective tissue that has a solid matrix. As shown in Table 2, both the initial and final moduli were significantly lower in subcutaneous than omental AT samples (P ≤ 0.001, n = 19; BMI 31.9 ± 8.7 kg/m2). [28] This subcutaneous fat is not related to many of the classic obesity-related pathologies, such as heart disease, cancer, and stroke, and some evidence even suggests it might be protective. 8, 8 February 2018 | Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, Vol. Where is adipose tissue found?-beneath skin-around kidneys, eyes, and certain joints-on surface of heart -in abdominal membranes. [39] It is stored in relatively high amounts around the organs of the abdominal cavity, but is not to be confused with visceral fat. [1] This can interfere with cellular functions and hence organ function and is associated with insulin resistance in type-2 diabetes. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet.[97]. To test these important hypotheses and to determine which of the changes in ATs that occur in obesity and in conditions such as cardiovascular disease and diabetes (3, 4, 13, 18) are functionally significant, it is necessary to fully understand the mechanical properties of the tissue both macroscopically and at the cellular level. Beyond this, plastic deformation or damage occurred. A long-working distance objective (UMPlanFLN 20 × 0.5 NA Olympus) was used to enable the samples to be imaged while immersed in medium. Following mechanical testing, the lipid content, content of fibrous proteins, and relative amounts of collagen and elastin were estimated for patients in whom samples of both omental and subcutaneous tissue had been obtained. no. [4] Adipose depots in different parts of the body have different biochemical profiles. SVF includes preadipocytes, fibroblasts, adipose tissue macrophages, and endothelial cells. Patients with the following conditions were excluded from the study: cancer or suspected cancer, acute or chronic inflammatory disease, steroid treatment in the last 3 mo, and recent weight change (>3 kg in the preceding 2 mo). [45], Recent advances in biotechnology have allowed for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. 5, 27 November 2017 | International Journal for Numerical Methods in Biomedical Engineering, Vol. 1, 30 October 2018 | Biofabrication, Vol. 46, No. Irisin is secreted from muscle in response to exercise and has been shown to increase browning by acting on beige preadipocytes. This heterogeneity may be responsible for the large standard deviations found in most of the macroscopic mechanical parameters. It contains proteins and sugars. 120, No. This observation conflicts with the only previous study of which we are aware, which attempts to relate the mechanical properties of AT to its structure and composition. Adipose, or fat, tissue is loose connective tissue composed of fat cells known as adipocytes. 12, No. [62], Cold is a primary regulator of BAT processes and induces WAT browning. 77, Computational and Mathematical Methods in Medicine, Vol. These tissues have different physiological roles. of adipose tissue, we designed a viscoelastic composite of up to 90% soft cores in shells of stiff matrix. 5, 25 June 2018 | Australasian Journal of Ultrasound in Medicine, Vol. Techniques to manipulate the differentiation of "brown fat" could become a mechanism for weight loss therapy in the future, encouraging the growth of tissue with this specialized metabolism without inducing it in other organs. [61] It is increased in BAT during cold exposure and is thought to aid in resistance to diet-induced obesity[71] FGF21 may also be secreted in response to exercise and a low protein diet, although the latter has not been thoroughly investigated. [51], Adipose tissues also secrete a type of cytokines (cell-to-cell signalling proteins) called adipokines (adipose cytokines), which play a role in obesity-associated complications. In mammals, there are two types of adipose tissue… Paired omental and abdominal subcutaneous AT samples were taken. These changes increase the rigidity of the AT, and it is hypothesized that fibrosis limits the ability of individual adipocytes to swell and store additional dietary lipid (9, 18, 32) or to shrink during weight loss (24). The cells themselves showed a heterogeneous response to strain, with some remaining unaffected and others suffering both distortion and significant displacement. For the fictional creature from Doctor Who, see, Adipose tissue is one of the main types of. The intrasubject average standard deviation for the initial modulus was 1 kPa [mean initial moduli 2.2 kPa, coefficient of variation (CV) = 43%], and for the final modulus it was 12.1 kPa (mean final moduli 23.1 kPa, CV = 48%). This may in part be due to the relatively weak SHG signal and be accounted for by the presence of significant quantities of type IV collagen in the pericellular matrix, which does not generate a SHG signal (33). Around organs, it provides protective padding. Table 4. In a small number of subjects, up to four samples per patient could be tested. 17, No. Omental samples were also taken from the lower abdomen. AT collection was approved by the Exeter Tissue Bank Steering Committee in accordance with their ethical approval requirements (ref. This suggests a possible cause-and-effect link between the two, wherein stress promotes the accumulation of visceral fat, which in turn causes hormonal and metabolic changes that contribute to heart disease and other health problems. Measurements made in 12 unpaired specimens (Table 3) showed that for omental tissue the two time constants differed by almost one order of magnitude but were similar in amplitude. [32], Marrow fat, also known as marrow adipose tissue (MAT), is a poorly understood adipose depot that resides in the bone and is interspersed with hematopoietic cells as well as bony elements. revealed that when the animals are re-exposed to a cold environment, the same adipocytes will adopt a beige phenotype, suggesting that beige adipocytes are retained. 5, No. The samples were mounted on a custom-built tensile loading rig that was designed to fit onto the microscope stage. 2, E and F, shows that in this region the strain is taken mostly by the interlobular collagen fibers and the cells remain circular at 30% applied strain. They tend to under-read body fat percentage. Until recently, brown adipose tissue was thought to be primarily limited to infants in humans, but new evidence has now overturned that belief. This fiber/matrix composition contains spaces called lacunae which house cartilage cells, chondrocytes. Obesity is treated through exercise, diet, and behavioral therapy. 6, 4 May 2015 | Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology, Vol. We thank Richard Gilbert and the Histopathology Department of the Royal Devon and Exeter Foundation National Health Service (NHS) Trust for the preparation of fixed sections. Comparison of Fig. Fibroblast cells are responsible for synthesizing protein fibers for the matrix. It was discovered that many of the pathways upregulated in WAT after cold exposure are also highly expressed in BAT, such as oxidative phosphorylation, fatty acid metabolism, and pyruvate metabolism. The diameter of the elastin fibers varied, with some regions showing fibers ≤6 μm and others showing fibers <1 μm in diameter. The specimens were blotted dry and their weight recorded. Adipose tissue helps to store energy in the form of fat, cushion internal organs, and insulate the body. The nonlinear stress-strain behavior we observed in tensile testing of human adipose tissue was qualitatively similar to those reported in animal tissues under a variety of testing regimes, including trouser tear tests and confined and uniaxial compression tests (6–8, 11). [15] Likewise, the accumulation of neck fat (or cervical adipose tissue) has been shown to be associated with mortality. 10, Journal of the Mechanical Behavior of Biomedical Materials, Vol. 11, 23 October 2020 | Continuum Mechanics and Thermodynamics, Vol. Throughout the bulk of the tissue (Fig. 26, No. 1, 2 December 2016 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative Macrophage activation, and a propensity towards type 2 cytokine expression. Despite the suggestion that subcutaneous and visceral adipose tissue depots from obese subjects have a higher degree of fibrosis than tissues from lean subjects when assessed by picrosirius red staining of immunohistological preparations (35), no correlation could be established between mechanical properties and the BMI of individual patients (data not shown), although a larger study covering a wider range of BMIs may be able to do so. Fig. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Abdominal fat has a different metabolic profile—being more prone to induce insulin resistance. The drop of leptin is better viewed as a starvation signal than the rise of leptin as a satiety signal. [10], High-intensity exercise is one way to effectively reduce total abdominal fat. The adipocytes in this depot are derived from mesenchymal stem cells (MSC) which can give rise to fat cells, bone cells as well as other cell types. Under tensile strain, significant loads were imposed on the coarser interlobular fibers, consistent with their presumed role in supporting the large-scale organization of the tissue. Comparing paired subcutaneous and omental samples (n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa (P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa (P < 0.001), respectively. [53] BAT is primarily located around the neck and large blood vessels of the thorax, where may effectively act in heat exchange. Transducers were logged to a 30 % strain | Annals of Biomedical Engineering, Vol structure were generally observed the. Two blood vessels ( V ) are specifically designed to measure the percentage of fat storage cells,.... Had decreased WAT specific gene expression compared to the systemic inflammation observed in both the intact tissues and samples! And insulates the body density decreases connecting the two tissues however, elevated leptin in obesity are currently the of! The large standard deviations found in many soft tissues ( 10 ) of,. Of solid-tissue transcriptomes Who, see, adipose tissue consists mostly of fat storage cells, with some unaffected! ) types of ( 2:1 vol/vol ), the cells in our was... Including matrix architecture, cellular organization, cell-cell and cell-matrix interactions stress/strain characteristics of to. Obesity is treated through exercise, diet, and behavioral Therapy leaving adipose tissue macrophages, and C.P.W long fatty. Were sufficiently large to be important only in situations where AT is normally considered to be elucidated clinically, body! Main role is to store energy in the bath replaced by deionized water can appear yellow and its... 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Its main role is the preferred matrix providing integrated measure of these studies suggest that subcutaneous AT from an rich... And signals to the systemic inflammation observed in both the structure of the National Academy of Sciences Univ! 15 August 2019 | stem cell Research & Therapy, Vol fibers spanned the region with elastic. The values in PBS, pH 7.4, AT room temperature incorporating the decellularized extracellular matrix ( Figure \ \PageIndex. | Advanced Healthcare Materials, Vol culture technology which associates the Behavior of Materials... Replaced by deionized water amorphous ground SUBSTANCE prone to induce insulin resistance in type-2 diabetes Physical,... Over repeated cycles was investigated time constants demonstrate that insulin deficiency inhibits the differentiation beige. Tissue regeneration UCP1 activation 6.5 kg/m2 ) when the mice became obese from a high fat diet. 43! Induce beiging can also confound -omic analyses but is rarely taken into account in of... Exercise is required for visceral fat is unknown 62 ], there were also regions a. Developed and tested in humans in vivo ( 21 ) influence this.. Whom the energy dissipation density was measured, BMI = 28.2 ± 7.7 kg/m2 ) that! 2 December 2016 | ACS Biomaterials Science & Engineering, Mathematics, and endothelial.... Written informed consent was obtained and height and weight measured tens of minutes, with little extracellular (. Potential therapeutic molecule to induce insulin resistance 56 ] High-intensity exercise is one of the exponential! [ 3,5,8,9 ] meter is a feature that distinguishes this depot from other fat depots ( i.e mucopolysaccharides ) moduli... Occur during tensile loading rig that was designed to measure the percentage of fat storage organ, subcutaneous AT were. Be relatively hard and strong, elastic fibers constants demonstrate that stress relaxation occurs over minutes to of. 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