Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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Highlights? TBLR1 controls cAMP-dependent lipolysis in adipocytes ? Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ? Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ? TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans     

人体内褐色脂肪组织及其生理功能

褐色脂肪组织(brown adipose tissue,BAT)在小型哺乳动物的非颤抖性产热、体温调节以及体重维持等方面都具有重要的生理功能.在人类中,曾一度认为褐色脂肪组织只在新生儿中存在,在成人体中不存在或数量甚微而没有生理意义.随着医学科技的发展,2009年采用监测癌症及癌症转移的氟化脱氧葡萄糖正电子发射计算机断层显像技术-X射线断层显像技术(18F-FDG PET-CT)检测到在成年人体内也存在功能性的褐色脂肪组织,此发现颠覆了传统的观念,也为人类对抗肥胖提供了新靶标.本文就褐色脂肪组织在人类体内的存在及其潜在的生理意义进行了概述.     

Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

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Intra-Abdominal Adipose Tissue Values Associated With Risk of Possessing Elevated Blood Lipids and Blood Pressure

Central fat distribution and more recently intra abdominal adipose tissue (IAF) have been associated with elevated cardiovascular risk factors (CRF). Despite increased interest in use of IAF for screening for CRF, interpretation of risk found in a specific IAF is difficult since regressions for estimating CRF from IAF have not been published. The purpose of this paper is to report IAF values that are likely to be associated with elevated CRF. One hundred forty-six healthy male subjects 30–71 years were evaluated for IAF and subcutaneous fat (computed tomography scan at 4th lumbar vertebra), height, body weight, % fat, various anthropometric measures, blood cholesterol (CHOL), HDL cholesterol (HDL), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Receiver-Operating-Characteristic curves (ROC) were used to develop IAF cutpoints associated with elevation of at least one established CRF criteria (CHOL=200, HDL=<35, SBP=140, DBP=90). A sensitivity/(1- specificity) curve estab lished the value of using IAF cutpoints for detecting elevated CRF. Likelihood ratios were used to identify optimal cutpoints. Two cutpoints were identified, 131 cm² with a relatively high L_pos ratio and 71 cm²with a relatively low L_neg. False positives associated with 131 cm² were 14% for one or more elevated CRF. False negatives associated with 71 cm² were 9% for one or more elevated CRF, 4% for two or more CRF, and 0% for three or more elevated CRF. This study clearly indicates that IAF above 131 cm²is related to elevated CRF and IAF below 71 cm² is associated with reduced cardiovascular risk.     

猪脂肪组织和原代脂肪细胞中GPR43基因的转录表达规律

根据GenBank已发表的人、小鼠及大鼠GPR43(G protein-coupled receptor 43)基因序列, 设计并合成一对引物, RT-PCR扩增获得猪GPR43基因cDNA, 并利用PCR技术检测该基因在不同猪种、不同发育阶段、不同部位脂肪组织及原代脂肪细胞中的转录表达规律。结果显示, 成功克隆猪GPR43 cDNA片段, 长度为486 bp (GenBank登陆号为EU122439); 同源性分析发现, 猪GPR43与人、小鼠和大鼠同源性达83%以上; GPR43 mRNA表达量在脂肪型猪种上显著高于瘦肉型猪种, 随月龄增长表达量逐渐上升, 且皮下脂肪表达量较内脏脂肪高; 在猪前体脂肪细胞诱导分化过程中, GPR43 mRNA表达量呈时间依赖性升高。揭示GPR43 mRNA表达与猪肥胖程度、年龄、脂肪沉积部位以及脂肪细胞分化程度密切相关。     

组织和发育特异性基因的远距离转录调控

远距离转录调控是指增强子、沉默子和隔离子等顺式作用元件参与的组织和发育特异性基因的表达调控。其调控元件可位于距转录基因很远的DNA区域,甚至分布于邻近基因内含子中。随着人类基因组计划和各种模式生物测序工作的完成,为大规模快速查找远距离调控元件提供了新的手段。由于基因组结构的复杂性,很难建立统一的基因表达调控模型,目前认为启动子与增强子的相互作用是组织和发育特异性基因成功表达的关键。另外,远距离转录调控机制一旦破坏还将导致疾病的发生。     

Brown Adipose Tissue Quantification in Human Neonates Using Water-Fat Separated MRI

There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction) were calculated. Neonatal scans (n = 22) were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (Δ_WAT-BAT = 38%, p<10⁻⁴). Repeated scans demonstrated a high voxelwise correlation for fat fraction (R_all = 0.99). BAT depot volume and fat fraction measurements showed high intra-rater (ICC_BAT,VOL = 0.93, ICC_BAT,FF = 0.93) and inter-rater reliability (ICC_BAT,VOL = 0.86, ICC_BAT,FF = 0.93). This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat fraction measurements.