Human Fat Tissue Research Articles

Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives.

Several therapeutic options have been developed to address the obesity epidemic and treat associated metabolic diseases. Despite the beneficial effects of surgery and drugs, effective therapeutic solutions have been held back by the poor long-term efficiency and detrimental side effects. The development of alternative approaches is thus urgently required. Fat transplantation is common practice in many surgical procedures, including aesthetic and reconstructive surgery, and is a budding future direction for treating obesity-related metabolic defects. This review focuses on adipose tissue transplantation and the recent development of cell-based therapies to boost the mass of energy-expenditure cells. Brown adipocyte transplantation is a promising novel therapy to manage obesity and associated metabolic disorders, but the need to have an abundant and relevant source of brown fat tissue or brown adipocytes for transplantation is a major hurdle to overcome. Current studies have focused on the rodent model to obtain a proof of concept of a tissue-transplantation strategy able to achieve effective long-term effects to reverse metabolic defects in obese patients. Future perspectives and opportunities to develop innovative human fat tissue models and 3D engineered hiPSC-adipocytes are discussed.

Measurement of absorption and reduced scattering coefficients in Asian human epidermis, dermis, and subcutaneous fat tissues in the 400- to 1100-nm wavelength range for optical penetration depth and energy deposition analysis (Errata).

.The errata correct errors that appeared in Table 2 of the published article.

Gene Expression of Angiotensin-Converting Enzyme 2 Receptor in Skin and the Implications for COVID-19.

Binding to the angiotensin-converting enzyme 2 (ACE2) receptor is a critical step for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter target cells. This enzyme is expressed in many human tissues including the lungs, but no research has demonstrated that SARS-CoV-2 can infect human skin or subcutaneous fat tissue, despite the increasing number of reported skin manifestations. The aim of this study was to investigate ACE2 gene expression in skin using a public database. A search of transcriptomic data sets from a public gene expression database to investigate ACE2 gene expression in human tissues. Human skin keratinocytes and basal cells express more ACE2 than lung epithelial cells. In contrast, both fibroblasts and melanocytes from human skin express less ACE2 than human lung epithelial cells. The high expression of ACE2 in keratinocytes and basal cells of human skin indicates that they may be directly susceptible to SARS-CoV-2 infection via the ACE2 receptor, especially in conditions of skin barrier dysfunction, and are therefore a potential target for the coronavirus.

Measurement of absorption and reduced scattering coefficients in Asian human epidermis, dermis, and subcutaneous fat tissues in the 400- to 1100-nm wavelength range for optical penetration depth and energy deposition analysis.

.Significance: In laser therapy and diagnosis of skin diseases, the irradiated light distribution, which is determined by the absorption coefficient and reduced scattering coefficient of the epidermis, dermis, and subcutaneous fat, affects the treatment outcome and diagnosis accuracy. Although values for and have been reported, detailed analysis for Asian skin tissues is still lacking.Aim: We present and measurements of Asian skin tissues in the 400- to 1100-nm wavelength range for evaluating optical penetration depth and energy deposition.Approach: The measurements with Asian human skin samples are performed employing a double integrating sphere spectrometric system and an inverse Monte Carlo technique. Using the measured parameters, the optical penetration depth and energy deposition are quantitatively analyzed.Results: The of the epidermis layer varies among different ethnic groups, while the of the other layers and the of all of the layers exhibit almost no differences. The analysis reveals that the optical penetration depth and the energy deposition affect the photodynamic therapy treatment depth and the heat production in skin tissue, respectively.Conclusions: The experimentally measured values of and for Asian skin tissues are presented, and the light behavior in Asian skin tissues is analyzed using a layered tissue model.

Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study.

Millions of plastic surgeries are performed worldwide every year with the objective of correcting lipodystrophies stemming from lesions, tumor resections, birth defects, and AIDS-associated antiretroviral therapy. Besides that, a large number of clinical research have assessed the outcome of procedures that rely on combinations of dermal fillers and autologous cells. However, little is known about the safety of these combinations and the localization of the injected cells. The aim of this study was to test the toxicity of a solution containing 1% hyaluronic acid (HA) and adipose-derived stromal cells (ASCs) from the human adipose tissue and to assess the localization of the injected cells, with and without HA, labeled with technetium-99m. Rats received subcutaneous and intraperitoneal injections of a solution containing 1% HA/adipose-derived stromal cells isolated from the human fat tissue. The animals were then observed for up to forty-two days. The solution tested in this study did not result in systemic, biochemical, or anatomic alterations that could represent toxicity symptoms. The association of HA and ASCs labeled with technetium-99m remained at the site of the injection within a period of twenty-four hours, as demonstrated by a whole-body imaging software fusion of SPECT and CT. In conclusion, our study shows that the subcutaneous and intraperitoneal injection of HA associated with adipose-derived stromal cells (ASCs) is safe. The association of HA and ASCs did not induce local or systemic toxicity. Thus, the administration of volume equal to or less than 0.2 mL of the agent filler (1 × 106 ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects.

Cytoplasmic p16 Is Expressed in Normal Brown Fat and Hibernomas.

White adipose tissue browning has emerged as a putative therapy of obesity, and studies in mice have shown that Cdkn2a is implicated in white-to-brown transition. However, the role of Cdkn2a product p16 has been never studied in human brown fat tissue. The aim of the study is to investigate the expression of p16 in normal brown fat and in hibernoma, a lipoma containing brown fat-like adipocytes. Ten normal brown fat tissues and 5 hibernomas were immunohistochemically studied for p16 expression. Nearby white adipose tissue was used for comparison. All brown fat and hibernomas specimens express p16 in a cytoplasmic manner. Neighboring white adipose tissue is negative for p16 expression. Thus, cytoplasmic p16 may be associated with fat tissue browning.

Abstract WP147: Cell-Free Fat Extract Promotes Angiogenesis in a Mouse Model of Cerebral Ischemia

Background: Adipose tissue and its derivatives including adipose-derived stem cells and stromal vascular fraction (SVF) showed effective in the treatment of ischemic stroke. However, cell-based therapy for clinical application has been hindered by limitations such as safety, immunogenicity issues, and difficulties in cell preservation, transportation, and phenotype control. Here, we aimed to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy for treating ischemic stroke. Methods: Cell-free aqueous extract from human fat tissue was obtained using mechanical emulsification method. Twenty adult CD-1 mice were subjected to 60-minute middle cerebral artery occlusion. Immediately after ischemia, 0.1 ml fat extract was intravenously injected into ischemic mice through tail vein every other day for 14 days. Brain atrophy volume and neurobehavioral outcomes were examined at 14 days after focal ischemia. The occurrence of angiogenesis was evaluated by immunostaining and ELISA, and growth factors contained in the fat extract was analyzed to explore the molecular mechanism of fat extract treatment. Results: Our results showed that brain atrophy volume reduced and neurobehavioral outcomes improved at 3 ,7 and 14 days of focal ischemia in the fat extract treated mice compared to the controls ( p <0.05). Furthermore, fat extract treatment increased microvessel density at 14 days after focal ischemia (p<0.05). ELISA showed that fat extract contained high levels of several growth factors such as HGF, VEGF, bFGF, BDNF, and GDNF. Conclusions: We developed a novel cell-free therapeutic agent, fat extract, produced from human adipose tissue. The fat extract contained high level of growth factors such as HGF, VEGF, bFGF, BDNF, and GDNF, which plays important role of promoting angiogenesis and reduced ischemic brain injury in the mouse brain, suggesting that the fat extract is a novel cell-free therapeutic agent in the treatment of ischemic stroke.

EfficientIn VitroDifferentiation of Adipose Tissue-Derived Mesenchymal Stem Cells Into the Cardiomyocyte Using Plant-Derived Natural Compounds

Various degenerative diseases, traumatic injuries and cancers are almost hard to treat with conventional therapies, causing death or at least permanent disability. The use of multipotent adipose-derived mesenchymal stem cells (ADMSCs) for cell-based therapeutic applications has lately drawn elevated attention primarily due to their potential for differentiation into mesodermal lineages, which can finally be converted into cardiomyocytes to replace present invasive methods used to treat cardiac diseases. However, some reports hindered their clinical implementation due to concerns about efficacy scalability and reproducibility. In this research, we tested the impacts of using multiple natural small molecules and plant extract on the effectiveness of differentiating human ADMSCs into the definitive mesoderm lineage and cardiac progenitors. First, mesenchymal stem cells separated from human adult fat tissue, are propagated and characterized using flow cytometry and appropriate markers for this purpose. Second, passage cells are transferred to 24 well plates and treated with various plant-derived small molecules — primarily one of the most preserved intracellular signals, WNT/[Formula: see text]-catenin stimulators including resveratrol, stilbene, and multiple plant extracts — and assessed their impacts on differentiation into the definitive mesoderm and cardiac lineages. Obtained results revealed that our suggested strategy to differentiation is more viable and safer than present approaches. Taken together, data presented here showed that in vitro differentiation using plant-derived small molecules could be a potential way to improve the effectiveness of their final differentiation into definitive cardiomyocytes for in vivo applications.

Plasma fibroblast growth factor 21 levels increase with ectopic fat accumulation and its receptor levels are decreased in the visceral fat of patients with type 2 diabetes

BackgroundFibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has beneficial effects on glucose and lipid metabolism. However, plasma FGF21 levels are paradoxically increased in type 2 diabetes...

Effect of vitamin D on muscle and its relationship with cancer cachexia

Vitamin D (VitD) and VitD receptors are closely related to human skeleton, muscle, fat and other tissues. The cachexia of the tumor is characterized by progressive loss of weight, mainly due to the decrease in the mass of skeletal and adipose tissue. There is no consensus on the role of VitD in the treatment of cachexia. This article reviews the role of VitD in cancer cachexia. Key words: Vitamin D; Neoplasms; Cachexia; Review

The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues

The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo.

Abstract 2160: Microfragmented human fat tissue is a natural scaffold for drug delivery: potential application in cancer chemotherapy

Abstract Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or fat tissue, can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural container of MSCs, to delivery PTX with the idea to improve local drug concentration and to prolong the therapeutic activity. Surprisingly, we found that both fresh but also devitalized MFAT (DMFAT) (by freezing/thawing procedure) were very effective biomaterials able to deliver and release significant amount of PTX, killing several human cancer cell lines in vitro with an impressive long lasting activity. In an orthotopic mice model of Neuroblastoma (NB) transplant, we found that DMFAT loaded with PTX prevents or delay NB relapse when placed in the surgical area of tumor resection, without any collateral toxicity. We concluded that MFAT, but also DMFAT, may work as natural biomaterials that can be used to localize and release anti-cancer molecules at the tumor site. In addition, the procedure to easily prepare DMFAT did not alter its natural scaffold structure. This suggest that such biomaterial may have a prominent role in the near future in many oncological applications to delivery anti-cancer drugs, helping to fight cancer in human. Citation Format: Giulio Alessandri, Valentina Coccè, Fabio Pastorino, Rita Paroni, Michele Deicas, Francesco Restelli, Carlo Tremolada, Angiola Berenzi, Eugenio Parati, Anna Teresa Brini, Giampietro Bondiolotti, Augusto Pessina, Mirco Ponzoni. Microfragmented human fat tissue is a natural scaffold for drug delivery: potential application in cancer chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2160.

1765-P: Adipose Sirtuin 6 Drives Macrophage Polarization Toward M2 through IL-4 Production and Maintains Systemic Insulin Sensitivity in Mice and Human

Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Here, using adipocyte-specific Sirt6 knockout mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of a canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experiment data, the degree of obesity and insulin resistance demonstrated by body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue. Disclosure M. Song: None.

Clinical Evaluation of the BTL-899 Device for Non-invasive Lipolysis on Human Fat Tissue

Clinical Evaluation of the BTL-899 Device for Non-invasive Lipolysis on Human Fat Tissue

Microfragmented human fat tissue is a natural scaffold for drug delivery: Potential application in cancer chemotherapy

Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or adipose tissue can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural scaffold of MSCs, to deliver PTX with the idea to improve local drug concentration and to prolong the therapeutic activity. Surprisingly, we found that both fresh but also devitalized MFAT (DMFAT) (by freezing/thawing procedure) were able to deliver and release significant amount of PTX, killing several human cancer cell lines in vitro with a long lasting activity. In an orthotopic mice model of Neuroblastoma (NB) transplant, DMFAT loaded with PTX prevents or delays NB relapse when placed in the surgical area of tumor resection, without any collateral toxicity. We concluded that MFAT, but also DMFAT, may represent very innovative natural biomaterials able to localize and release anti-cancer molecules at the tumor site, helping to fight cancer in human.

In Vivo Dynamics and Phase State of Natural Lipid Droplets

All organisms store lipids as energy resource for metabolism. Such lipids are accumulated in the form of intracellular droplets. The structure of the lipid droplet is complex. The hydrophobic core represents a mix of un- and saturated triglycerides, enclosed by an amphiphilic shell of phospholipids with embedded proteins. Uncovering intrinsic biophysical properties of lipid droplets in living cells of various organisms is crucial for metabolism manipulation or reducing lipid storage. The type and organization of lipids affect their phase state and microscopic dynamics in the droplet. We characterized lipid droplets in the cells of fresh human and porcine subcutaneous fat tissues, as well as yeast cells using quasi-elastic neutron scattering, probing the molecular motions in a time scale of 6-400 picoseconds and a length scale of 3-20 Angstroms. The detected two-component dynamics in the droplet is associated with lipid unrestricted diffusion (D ∼ 0.006 A2/ps) and motions of its hydrocarbon chains (D ∼ 0.2 A2/ps) in a restricted volume (5-12 A). The dynamics of lipids is significantly reduced below 305 K and 266 K in porcine and human tissues, respectively, due to a first-order phase transition of lipids from fluid to gel (similar to synthetic lipid bilayer). The lipid phase change in human tissue is confirmed and enhanced at applied pressure of 90 bars. However, lipid droplets in the yeast cells remain in a fluid-like state within range of 280-310 K. We believe that phase behavior of lipid droplets is different in the cells of tissues and microorganism due to lipid composition, which was investigated by mass spectrometry. Lipid packing in the droplet is tight in the tissues, having mostly saturated lipids, and loose in the yeast droplet, having equal proportions of un- and saturated lipids.

Tissue-mimicking gelatin scaffolds by alginate sacrificial templates for adipose tissue engineering

When adipose tissue (AT) is impaired by trauma or disease, AT engineering could provide a shelf-ready structural and functional restoration as alternative to current clinical treatments, which mainly aim at aesthetic replacement. Yet, the lack of an efficient vascular network within the scaffolds represents a major limitation to their translation application in patients. Here, we propose the use of microstructured crosslinked gelatin hydrogels with an embedded prevascular channel as scaffolding materials for AT engineering. The scaffolds are fabricated using – simultaneously – alginate-based microbeads and 3D printed filaments as sacrificial material encapsulated in gelatin at the point of material fabrication and removed post-crosslinking. This method yields the formation of microstructures that resemble the micro-architecture of physiological human fat tissue and of microvessels that can facilitate vascularization through anastomosis with patients’ own blood vessels. The cytocompatible method used to prepare the gelatin scaffolds showed structural stability over time while allowing for cell infiltration and protease-based remodeling/degradation. Scaffolds’ mechanical properties were also designed to mimic the one of natural breast adipose tissue, a key parameter for AT regeneration. Scaffold’s embedded channel (∅ = 300–400 µm) allowed for cell infiltration and enabled blood flow in vitro when an anastomosis with a rat blood artery was performed using surgical glue. In vitro tests with human mesenchymal stem cells (hMSC) showed colonization of the porous structure of the gelatin hydrogels, differentiation into adipocytes and accumulation of lipid droplets, as shown by Oil Red O staining. Statement of SignificanceThe potential clinical use of scaffolds for adipose tissue (AT) regeneration is currently limited by an unmet simultaneous achievement of adequate structural/morphological properties together with a promoted scaffold vascularization. Sacrificial materials, currently used either to obtain a tissue-mimicking structure or hollow channels to promote scaffold’ vascularization, are powerful versatile tools for the fabrication of scaffolds with desired features. However, an integrated approach by means of sacrificial templates aiming at simultaneously achieving an adequate AT-mimicking structure and hollow channels for vascularization is missing. Here, we prove the suitability of crosslinked gelatin scaffolds obtained by using sacrificial alginate microbeads and 3D printed strands to achieve proper features and hollow channels useful for scaffolds vascularization.

Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy

BackgroundThe proangiogenic capacity of adipose tissue and its derivatives has been demonstrated in a variety of studies. The paracrine mechanism of the cellular component is considered to play a critical role in the regenerative properties of these tissues. However, cell-based therapy for clinical application has been hindered by limitations such as safety, immunogenicity issues, and difficulties in cell preservation, transportation, and phenotype control. In the current study, we aimed to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy.MethodsWe developed a novel physical approach to produce a cell-free aqueous extract from human fat tissue (fat extract (FE)). The therapeutic potential of FE was investigated in the ischemic hindlimb model of nude mice. After establishment of hindlimb ischemia with ligation of the left femoral artery and intramuscular injection of FE, blood perfusion was monitored at days 0, 7, 14, 21, and 28. Tissue necrosis and capillary density were evaluated. Enzyme-linked immunosorbent assay was used to analyze the growth factors contained in FE. Moreover, the proliferation, migration, and tube formation ability were tested on human umbilical vein endothelial cells (HUVECs) in vitro when treated with FE. The proangiogenic ability of FE was further assessed in an in-vivo Matrigel plug assay.ResultsFE was prepared and characterized. The intramuscular injection of FE into the ischemic hindlimb of mice attenuated severe limb loss and increased blood flow and capillary density of the ischemic tissue. Enzyme-linked immunosorbent assay showed that FE contained high levels of various growth factors. When added as a cell culture supplement, FE promoted HUVEC proliferation, migration, and tube formation ability in a dose-dependent manner. The subcutaneous injection of Matrigel infused with FE enhanced vascular formation.ConclusionsWe developed a novel cell-free therapeutic agent, FE, produced from human adipose tissue. FE was able to attenuate ischemic injury and stimulate angiogenesis in ischemic tissues. This study indicates that FE may represent a novel cell-free therapeutic agent in the treatment of ischemic disorders.

Endothelial Differentiated Adipose-Derived Stem Cells Improvement of Survival and Neovascularization in Fat Transplantation.

Adipose-derived stem cells (ASCs) assisted lipotransfer have been considered to facilitate the survival of fat grafts. However, emerging evidence of insufficient vascularization is another obstacle for fat graft survival in cell-assisted lipotransfer. This study evaluated if endothelial phenotype ASCs with fat lipoaspirate improves survival and neovascularization in fat transplantation. ASCs were isolated from human periumbilical fat tissue and cultured in endothelial growth medium for 2 weeks. Fat lipoaspirate was mixed with fresh adipose stroma vascular fraction (SVF), endothelial differentiated ASCs (EC/ASCs), and fat lipoaspirate alone. Three fat mixtures were subcutaneously injected into the adult male Sprague-Dawley rat's dorsum at 3 locations. At 8 weeks after transplantation, the grafted fat lipoaspirates were harvested, and the extracted fat was evaluated using photographic, survival weights measurements and histological examination. Neo-vascularization was quantified by immunofluorescence and real-time RT-PCR. Grafts from the EC/ASC assisted group had a higher survival rate, morphologic integrity, and most uniform lipid droplets. They also revealed less inflammation and fibrosis with increased number of vessels by histological and immunofluorescence analysis. Quantitative RT-PCR analysis indicated that the expression levels of EC-specific markers of CD31 and vWF were higher in the EC/ASC group compared with in the control and fat with SVF transplants. These results indicated that co-implantation of fat lipoaspirate with ASCs differentiated toward an endothelial phenotype improves both survival and neovascularization of the transplanted fat lipoaspirate, which might provide benefits and represents a promising strategy for clinical application in autologous fat transplantation.

Study of the association of Trp64Arg mutation of beta three adrenergic receptor with obesity in Saudi population

Introduction: Beta three adrenergic receptor (ADRB3) is an adrenergic receptor that induces activation of adenylate cyclase located mainly in adipose tissue and is involved in the thermogenesis of brown fat tissue and in the regulation of lipolysis. Agonists of ADRB3 are found to induce the thermogenesis process of human brown fat tissue and thus believed to be excellent anti-obesity targets. The most studied single nucleotide polymorphism (SNP) of ADRB3 is rs4994. Inconsistent findings have been found in earlier studies about the association of rs4994 polymorphisms with obesity among different populations. The association of ADRB3/rs4994 polymorphism with obesity among the Saudi population is unknown. This study aimed to investigate the association of ADRB3/rs4994 polymorphism with obesity, blood lipids and blood pressure in the Saudi population.&#x0D; Method: This study was a case control study involving 88 obese healthy volunteers and 84 non-obese (controls) volunteers recruited from the King Khaled University Hospital (KKUH), Riyadh City, Saudi Arabia. Using KASPTM (Competitive Allele-Specific PCR) the rs4994 genotype for each participant was determined. The frequency, distribution, and association of each genotype with body mass index (BMI) and lipid profile were calculated.&#x0D; Results: The distribution of CC, TT and CT genotypes in the study population was 0.37, 0.06 and 0.56, respectively. The heterozygote CT genotype was associated with a reduced risk of obesity (odds ratio (OR)=0.4398, 95%CI=0.2338 to 0.8277, P-value=0.010). It was more frequent in the non-obese participants compared to the obese participants (67.9% vs. 44.3%, respectively). Moreover, participants with the CT genotype had a significantly lower BMI (P=0.004). In contrast, the CC genotype was associated with an increased risk of obesity (OR=2.5, 95%CI=1.3467 to 4.8758, P-value=0.004). The frequency of the CC genotype was higher in obese participants compared to the non-obese ones (46.6% vs. 28.6%, respectively). Participants with the CC genotype demonstrated a significantly higher BMI than participants with the CT or TT genotypes (Q= 4.5, P=0.004). The TT genotype had no significant effects on the participants’ BMI (OR=2.9, 95%CI=0.7563 to 11.5759, P value=0.11), and it was higher in obese compared to non-obese participants (9.1% vs. 3.6%, respectively). No significant effect of ADRB3/rs4994 polymorphism on blood lipid profile or blood pressure was observed.&#x0D; Conclusion: The findings of this study suggested that the heterozygote CT genotype of the ADRB3/rs4994 polymorphism is associated with a reduced risk of obesity among the Saudi population. In the future, larger scale studies are required to further confirm these observations.