Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women

肥胖女性皮下脂肪分布的细胞动力学

• 批准号: 8317856
• 负责人: YOURKA Dimova TCHOUKALOVA
• 金额: $ 4.14万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-12 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8317856
• 关键词: 2,4-thiazolidinedione; Abdomen; Adipocytes; Adipose tissue; Agonist; Antidiabetic Drugs; Apple; Biomedical Research; Blood Vessels; Body fat; Cell Aging; Cell Culture Techniques; Cells; Chronic; Comorbidity; Coupled; DNA; Data; Deposition; Deuterium; Development; Environment; Environmental Risk Factor; Event; Fatty acid glycerol esters; Goals; Growth; Health; Hip region structure; Human; Hyperplasia; Hypertrophy; Individual; Inflammatory; Inflammatory Response; Insulin Resistance; Intervention; Intrinsic factor; Kinetics; Lead; Leg; Longevity; Longitudinal Studies; Measures; Mediating; Metabolic; Morphology; Obesity; Pear; Phenotype; Physiology; Pioglitazone; Placebos; Plastics; Prevention; Prevention strategy; Regulation; Reporting; Research; Research Personnel; Risk; Shapes; Signal Transduction; Site; Stimulus; Tail; Techniques; Testing; Thiazolidinediones; Waist-Hip Ratio; Weight; Woman; Work; adipokines; drinking water; experience; glycemic control; improved; in vivo; lipid biosynthesis; metabolic abnormality assessment; prevent; progenitor; response; stable isotope; subcutaneous; tool

DESCRIPTION (provided by applicant): Adipose tissue expandability and the distribution of stored fat in the body are stronger predictors of health risk. A better understanding of the factors that determine regional fat mass growth may lead to developing new strategies for prevention or treatment of metabolic complications of obesity. The objective of this proposal is to study the responsiveness of lower- body fat mass, the inflammatory state of upper-body fat, ectopic fat, and insulin resistance to adipogenic stimulation in upper-body obese (UBO) women waist-to hip ratio (WHR) >0.85 and lower-body obese (LBO) women with WHR <0.75. Adipogenesis will be stimulated using pioglitazone (Pio). The hypothesis is that in UBO; adipogenesis in femoral fat is impaired, which leads to ectopic fat deposition, promoting insulin resistance. On the other hand, the ScA depot in UBO undergoes hypertrophy, leading to a chronic inflammatory state of the adipose tissue and consequential insulin resistance. Our specific aims are to test that: Aim 1. Impaired adipogenesis in the Sc fat of UBO women contributes to impaired adipogenesis in UBO women and to a) Limited leg fat expandability, which promotes insulin resistance via ectopic fat deposition; and b) The inflammatory response of upper-body fat which contributes to insulin resistance via inflammatory adipokines.; Aim 2. Cellular senescence contributes to impaired adipogenesis in UBO women and to identify candidate intrinsic or environmental factors that cause the depot-specific adipogenic regulation. UBO and LBO women (30 each) will be treated with Pio or placebo for 16 weeks. The adipocyte progenitor number, adipogenesis, the morphology and inflammatory response of adipose tissue, and systemic glycemic control will be determined before, during, and after the intervention. Distribution of fat in fat depots and ectopic sites will be measured. Stromal vascular cultures will be employed to assess preadipocyte kinetics in ScA and Sc femoral (ScF) fat depots and the mechanisms of their regulation. We will also assess in vivo Sc regional adipogenesis by measuring incorporation of deuterium (D) from D2O drinking water into the DNA of plastic adherent stroma-vascular (SV) cells by determining their fractional replacement (fSV cells).

描述（由申请人提供）：脂肪组织的可扩展性和体内储存的脂肪的分布是健康风险的更强预测指标。更好地了解决定区域脂肪量增长的因素可能会导致制定预防或治疗肥胖代谢并发症的新策略。该提案的目的是研究下体脂肪，上体脂肪，异位脂肪的炎症状态和胰岛素耐药性对上体肥胖（UBO）女性腰围髋关节（WHR）（WHR）> 0.85> 0.85和下男孩肥胖（LBO）女性WHR <0.75 <0.75 <0.75 <0.75。脂肪形成将使用吡格列酮（PIO）刺激。假设是在UBO中；股脂肪中的脂肪形成受损，从而导致异位脂肪沉积，从而促进胰岛素抵抗。另一方面，UBO中的SCA仓库经历了肥大，导致脂肪组织的慢性炎症状态和胰岛素抵抗。我们的具体目的是测试：目标1。在UBO妇女的SC脂肪中脂肪生成受损，导致UBO妇女的脂肪生成受损，并使A）有限的腿部脂肪膨胀性，从而通过异位脂肪沉积促进胰岛素耐药性； b）上体脂肪的炎症反应，这有助于通过炎症脂肪因子抗胰岛素的耐药性。 AIM 2。细胞衰老有助于UBO妇女的脂肪生成受损，并确定导致居民的固有或环境因素，从而导致仓库特异性的脂肪生成调节。 UBO和LBO妇女（每个30个）将用PIO或安慰剂治疗16周。将在干预之前，期间和之后确定脂肪细胞祖细胞数，脂肪生成，脂肪和炎症反应以及全身性血糖控制。将测量脂肪库和异位部位中脂肪的分布。将采用基质血管培养物来评估SCA和SC股骨（SCF）脂肪库中的前细胞动力学及其调节机制。我们还将通过测量从D2O饮用水中掺入氘（D），通过确定其分数替换（FSV细胞）来评估体内SC区域脂肪形成。