-
世界卫生组织将肥胖定义为可能损害人体健康的过度脂肪积累，体重指数（body mass index，BMI）≥30 kg/m2[1]，中国人的肥胖标准为BMI>28 kg/m2[2]。肥胖增加了心血管疾病、代谢性疾病和恶性肿瘤等疾病的发生风险[3]。Lauby-Secretan等[4]的研究结果显示，肥胖与甲状腺癌、结直肠癌和绝经后乳腺癌等13种癌症的发生相关。
肥胖引发的临床问题主要与脂肪组织的分布和类型密切相关。人体内的脂肪组织主要分为白色脂肪组织（white adipose tissue，WAT）和棕色脂肪组织（brown adipose tissue，BAT）2种类型[5]。肥胖的特征是WAT的过度积累[6]，而诱导和激活BAT是治疗肥胖的有效方法[7]。BAT在肥胖者中含量较少、活性较低，其与BMI和体脂率呈负相关[7]。WAT主要包括内脏脂肪组织（visceral adipose tissue，VAT）和皮下脂肪组织（subcutaneous adipose tissue，SAT）[8]。Kuipers等[9]的研究结果显示，VAT的积累与多种疾病及其预后相关。
大部分研究者均使用BMI等作为肥胖的评估指标，以研究肥胖与疾病的关系[1,3-4]。脂肪组织的不同解剖分布模式对人体健康有重大影响[10]。WAT的过度积累能反映肥胖的本质，因此，对脂肪组织分布和类型的研究至关重要。CT和MRI在定量脂肪组织方面具有良好的密度分辨率、较高的准确率和可重复性[11]；PET/CT可同时获取脂肪组织的体积和代谢情况，且不同PET显像剂、显像方法和测量方法均为肥胖的评估提供了多种选择[12]。
-
WAT中VAT的18F-FDG摄取值高于SAT，这表明VAT的代谢活性更高[13]。VAT不仅能储存脂质，还具有活跃的内分泌和旁分泌功能，其可分泌细胞因子和生物活性介质，促进炎症进程[14]。通过18F-FDG PET/CT显像评估组织炎症的原理是葡萄糖的代谢机制[15]，目前其已被用于研究WAT的葡萄糖代谢机制。
-
肥胖增加了心血管疾病的发生风险，有研究者通过18F-FDG PET/CT显像获取心血管周围脂肪组织的体积和代谢信息，评估其与心血管疾病发生风险的相关性[16-17]。Kwon等[16]评估了SAT和VAT的体积和代谢信息与心血管疾病发生风险因素的相关性，结果显示，SAT和VAT的体积与多种心血管疾病发生的风险因素呈正相关，脂肪组织的SUV提高了心血管疾病预测模型的性能。Bucerius等[17]发现，不同部位（颈部、胸骨前区和心包）WAT的18F-FDG摄取与颈动脉和主动脉的18F-FDG摄取呈正相关，动脉18F-FDG摄取是炎症的一种标志。
-
流行病学研究结果显示，肥胖与恶性肿瘤的发生存在因果关系[4]。Hyun等[18]发现，在乳腺癌尤其是超重的乳腺癌女性患者中，肿瘤SUVmax越高，预后越差。Pahk等[19]探讨了绝经后腔内型乳腺癌患者术前18F-FDG PET/CT评估的VAT代谢与腋窝淋巴结转移的关系，用VAT SUVmax与SAT SUVmax的比值评估VAT的代谢水平，结果显示，其与肥胖者的腋窝淋巴结转移呈正相关，并且与绝经后腔内型乳腺癌患者的全身炎症指标相关；在SUVmax的基础上，VAT SUVmax与SAT SUVmax的比值提高了预测腋窝淋巴结转移的准确率，其可被用作肥胖相关恶性肿瘤侵袭性的潜在指标，并有助于评估绝经后腔内型乳腺癌患者的肥胖治疗干预效果。还有研究结果显示，通过18F-FDG PET/CT显像评估的VAT代谢水平升高是甲状腺癌、多发性骨髓瘤患者预后的相关因素，VAT 代谢水平升高可能是这些恶性肿瘤早期的标志[20-21]。
-
有研究结果显示，依据BMI诊断的肥胖会增加患者患痴呆症的风险，而18F-FDG在阿尔茨海默病（alzheimer disease，AD）的诊断中发挥着重要作用，18F-FDG代谢水平的降低先于临床症状的出现，颞顶叶和后扣带回皮质的18F-FDG代谢水平降低可提供AD发展的时间信息[22]。Volkow等[23]的研究结果显示，以往多项关于肥胖会增加AD的风险及其与健康个体之间相关性的研究，揭示了高BMI和前额叶低代谢的相关性。Kim等[24]采用18F-FDG PET/CT评估健康老年人VAT与AD发生风险的关系，未发现二者之间有相关性，但这项研究并未涉及VAT代谢与脑葡萄糖代谢的相关性。
-
已有研究结果显示，心血管周围WAT的 18F-FDG摄取与动脉炎症呈正相关[17]。Pahk等[25]研究了肥胖女性VAT炎症与全身炎症指标的相关性，以评估运动对VAT炎症的改善：受试者在运动前（基线水平）和完成3个月的运动计划后均接受18F-FDG PET/CT检查，采用SUVmax和平均标准化摄取值（SUVmean）评估VAT的代谢水平；在肥胖女性中，VAT的SUVmax与全身炎症指标相关，运动降低了VAT的SUVmax，并减弱了其与全身炎症指标的相关性；尽管二者同时降低，但其相关性的机制尚不明确；另外，随着运动时间的增加，VAT SUVmax约下降到基线水平的50%，研究者猜想这可能是正常人群VAT SUVmax的固有水平，但这一结果的机制有待进一步研究。
-
BAT通常在冷暴露或交感神经受刺激下被激活，可增加能量消耗，降低体脂率，进而降低心血管疾病的发生风险。BAT在肥胖及其继发的代谢性疾病患者中的含量较少[7]，Li等[26]的研究结果也显示，局部热疗激活WAT棕色化可治疗肥胖。2003年，Cohade等[27]首次在18F-FDG PET/CT显像中观察到了BAT，该研究结果显示，成年人体中存在代谢活跃的BAT，且其与低BMI、低龄、低温、女性和葡萄糖代谢水平降低相关。18F-FDG PET/CT是目前无创检测BAT的“金标准”。
18F-FDG PET/CT BAT阳性与多种疾病（包括2型糖尿病、恶性肿瘤）的治疗和预后密切相关[28-30]。Becher等[28]回顾性分析了52 487例患者的18F-FDG PET/CT检查结果，以BAT阳性摄取与否进行分类，BAT阳性患者2型糖尿病和心血管疾病（包括冠状动脉疾病、脑血管疾病、充血性心力衰竭、高血压和血脂异常）的发病率显著降低；该研究结果还显示，BAT阳性发生率与恶性肿瘤的发生部位相关，其与嘴唇、口咽、乳房、女性生殖器官、淋巴瘤、骨、关节及关节软骨部位的恶性肿瘤发病率呈正相关，而与消化器官、眼、神经系统和网织内皮器官部位的恶性肿瘤发病率呈负相关。
应用18F-FDG PET/CT评估肥胖者BAT代谢情况的研究较少。Herz等[31]对严重肥胖者的BAT代谢情况进行了小样本量研究，40名Ⅱ~Ⅲ级肥胖者（32名女性、8名男性，BMI≥35 kg/m2）经长达150 min的冷刺激后，35%的患者18F-FDG PET/CT显像呈BAT阳性（均为女性且体重较低者），其VAT含量较BAT阴性的患者减少了28.8%，这表明肥胖者中也存在代谢活跃的BAT，18F-FDG摄取减少与肥胖本身无关，但与VAT含量增加有关，代谢活跃的BAT与较健康的肥胖代谢表型有关。
-
综上，肥胖增加了恶性肿瘤等疾病的发生风险，多伴随WAT分布增多，BAT分布减少。18F-FDG PET/CT可评估肥胖者不同类型脂肪组织的代谢活性，实现了从代谢水平研究脂肪组织与疾病的相关性，其中，WAT尤其是VAT的18F-FDG代谢与疾病的发生风险、预后呈正相关。BAT代谢活性与女性、低体重、外界温度降低和相对低龄相关。肥胖者也存在代谢活跃的BAT，并可能与较健康的肥胖代谢表型有关，但其目前仅为小样本量研究。肥胖者不同部位和类型脂肪组织与疾病发生的相关分子机制及其18F-FDG代谢水平尚不明确，特别是BAT代谢活跃的原因还需要大样本量的临床循证证据。另外不同PET分子影像探针及多维代谢定量参数的应用可为肥胖相关疾病提供更有价值的参考。
利益冲突 所有作者声明无利益冲突
作者贡献声明 李肖萌负责命题的提出与设计、综述的撰写；胡奕奕、崔曹哲负责综述的修改；武志芳负责综述框架的设计、修改、审阅及最终版本的修订
18F-FDG PET/CT在肥胖中的应用进展
Application and progress of 18F-FDG PET/CT in obesity
-
摘要: 肥胖已成为一种严重危害人类健康的重要问题，其与心血管疾病、代谢性疾病和恶性肿瘤等密切相关。评估肥胖最常用的指标为体重指数、腰围和腰臀比等，但随着对肥胖发病机制的深入研究，不同部位及类型的脂肪组织得以区分。人体内的脂肪组织分为白色脂肪组织（WAT）和棕色脂肪组织（BAT）2种类型。WAT的过度积累是肥胖的特征，而BAT在肥胖者中活性较低。18F-FDG PET/CT 可以同时获取不同部位及类型脂肪组织的体积和代谢情况。笔者从不同脂肪库的角度综述18F-FDG PET/CT在肥胖中的应用进展。
-
关键词:
- 肥胖症 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术 /
- 体层摄影术，X线计算机
Abstract: Obesity has become an important problem that seriously endangers human health, which is closely related to cardiovascular diseases, metabolic diseases, and malignant tumors. The most commonly used indicators to assess obesity are body mass index, waist circumference, waist-to-hip ratio and so on. However, with the in-depth research on the pathogenesis of obesity, different parts and types of adipose tissue can be distinguished. There are two types of adipose tissue in the human body: white adipose tissue (WAT) and brown adipose tissue (BAT). Excessive accumulation of WAT is characteristic of obesity, while BAT is less active in obese individuals. 18F-FDG PET/CT can simultaneously acquire the volume and metabolism of different parts and types of adipose tissue. The authors review the application and progress of 18F-FDG PET/CT in obesity from the perspective of different adipose depots. -
[1] Sung H, Siegel RL, Torre LA, et al. Global patterns in excess body weight and the associated cancer burden[J]. CA Cancer J Clin, 2019, 69(2): 88−112. DOI: 10.3322/caac.21499. [2] 王友发. 中国居民肥胖防治专家共识[J/OL]. 中国预防医学杂志, 2022, 23(5): 1−19[2022-06-01]. https://kns.cnki.net/kcms/detail/11.4529.r.20220520.1341.003.html. DOI: 10.16506/j.1009-6639.2022.05.001.
Wang YF. Expert consensuson obesity prevention and treatment in china[J/OL]. Chin Prev Med, 2022, 23(5): 1−19[2022-06-01]. https://kns.cnki.net/kcms/detail/11.4529.r.20220520.1341.003.html. DOI: 10.16506/j.1009-6639.2022.05.001.[3] Blüher M. Obesity: global epidemiology and pathogenesis[J]. Nat Rev Endocrinol, 2019, 15(5): 288−298. DOI: 10.1038/s41574-019-0176-8. [4] Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer-viewpoint of the IARC working group[J]. N Engl J Med, 2016, 375(8): 794−798. DOI: 10.1056/NEJMsr1606602. [5] Hyvönen MT, Spalding KL. Maintenance of white adipose tissue in man[J]. Int J Biochem Cell Biol, 2014, 56: 123−132. DOI: 10.1016/j.biocel.2014.09.013. [6] 舒凤, 王梦伊, 张世武, 等. 脂肪组织炎性反应的研究进展[J]. 基础医学与临床, 2021, 41(7): 1052−1055. DOI: 10.16352/j.issn.1001-6325.2021.07.021.
Shu F, Wang MY, Zhang SW, et al. Research progress of inflammatory response of adipose tissue[J]. Basic & Clin Med, 2021, 41(7): 1052−1055. DOI: 10.16352/j.issn.1001-6325.2021.07.021.[7] Oliver P, Lombardi A, De Matteis R. Editorial: insights into brown adipose tissue functions and browning phenomenon[J/OL]. Front Physiol, 2020, 11: 219[2022-02-23]. https://www.frontiersin.org/articles/10.3389/fphys.2020.00219/full. DOI: 10.3389/fphys.2020.00219. [8] Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome[J]. Endocr Rev, 2000, 21(6): 697−738. DOI: 10.1210/edrv.21.6.0415. [9] Kuipers AL, Zmuda JM, Carr JJ, et al. Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in African ancestry men[J]. Atherosclerosis, 2017, 263: 198−204. DOI: 10.1016/j.atherosclerosis.2017.06.030. [10] Cespedes Feliciano EM, Kroenke CH, Caan BJ. The obesity paradox in cancer: how important is muscle?[J]. Annu Rev Nutr, 2018, 38: 357−379. DOI: 10.1146/annurev-nutr-082117-051723. [11] 邵小南, 邵晓梁, 蒋振兴, 等. 棕色脂肪组织影像学技术的研究进展[J]. 中华核医学与分子影像杂志, 2019, 39(11): 685−687. DOI: 10.3760/cma.j.issn.2095-2848.2019.11.012.
Shao XN, Shao XL, Jiang ZX, et al. Research progress of brown adipose tissue imaging technology[J]. Chin J Nucl Med Mol Imaging, 2019, 39(11): 685−687. DOI: 10.3760/cma.j.issn.2095-2848.2019.11.012.[12] Din MU, Raiko J, Saari T, et al. Human brown fat radiodensity indicates underlying tissue composition and systemic metabolic health[J]. J Clin Endocrinol Metab, 2017, 102(7): 2258−2267. DOI: 10.1210/jc.2016-2698. [13] Monteiro AM, Ferreira G, Duarte H. Metabolic activity in the visceral and subcutaneous adipose tissues by FDG-PET/CT in obese patients[J]. Acta Med Port, 2017, 30(11): 813−817. DOI: 10.20344/amp.8712. [14] Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update[J]. Physiol Rev, 2013, 93(1): 359−404. DOI: 10.1152/physrev.00033.2011. [15] Tarkin JM, Joshi FR, Rudd JHF. PET imaging of inflammation in atherosclerosis[J]. Nat Rev Cardiol, 2014, 11(8): 443−457. DOI: 10.1038/nrcardio.2014.80. [16] Kwon HW, Lee SM, Lee JW, et al. Association between volume and glucose metabolism of abdominal adipose tissue in healthy population[J]. Obes Res Clin Pract, 2017, 11(5 Suppl 1): S133−143. DOI: 10.1016/j.orcp.2016.12.007. [17] Bucerius J, Mani V, Wong S, et al. Arterial and fat tissue inflammation are highly correlated: a prospective 18F-FDG PET/CT study[J]. Eur J Nucl Med Mol Imaging, 2014, 41(5): 934−945. DOI: 10.1007/s00259-013-2653-y. [18] Hyun SH, Ahn HK, Lee JH, et al. Body mass index with tumor 18F-FDG uptake improves risk stratification in patients with breast cancer[J/OL]. PLoS One, 2016, 11(10): e0165814[2022-02-23]. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165814. DOI: 10.1371/journal.pone.0165814. [19] Pahk K, Joung C, Kim S. Visceral fat metabolic activity evaluated by preoperative 18F-FDG PET/CT significantly affects axillary lymph node metastasis in postmenopausal luminal breast cancer[J/OL]. Sci Rep, 2020, 10(1): 1348[2022-02-23]. https://www.nature.com/articles/s41598-020-57937-4. DOI: 10.1038/s41598-020-57937-4. [20] Pahk K, Choi S, Kim S. Functional visceral fat activity evaluated by preoperative F-18 FDG PET/CT predicts regional lymph node metastasis in differentiated thyroid cancer[J]. Clin Endocrinol (Oxf), 2018, 88(6): 963−968. DOI: 10.1111/cen.13604. [21] da Cunha Júnior AD, Silveira MN, Takahashi MES, et al. Visceral adipose tissue glucose uptake is linked to prognosis in multiple myeloma patients: an exploratory study[J]. Clin Nutr, 2021, 40(6): 4075−4084. DOI: 10.1016/j.clnu.2021.02.010. [22] Bohnen NI, Djang DSW, Herholz K, et al. Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: a review of the recent literature[J]. J Nucl Med, 2012, 53(1): 59−71. DOI: 10.2967/jnumed.111.096578. [23] Volkow ND, Wang GJ, Telang F, et al. Inverse association between BMI and prefrontal metabolic activity in healthy adults[J]. Obesity (Silver Spring), 2009, 17(1): 60−65. DOI: 10.1038/oby.2008.469. [24] Kim J, Choi KH, Cho SG, et al. Association of muscle and visceral adipose tissues with the probability of Alzheimer's disease in healthy subjects[J/OL]. Sci Rep, 2019, 9(1): 949[2022-02-23]. https://www.nature.com/articles/s41598-018-37244-9. DOI: 10.1038/s41598-018-37244-9. [25] Pahk K, Kim EJ, Joung C, et al. Exercise training reduces inflammatory metabolic activity of visceral fat assessed by 18F-FDG PET/CT in obese women[J]. Clin Endocrinol (Oxf), 2020, 93(2): 127−134. DOI: 10.1111/cen.14216. [26] Li Y, Wang DM, Ping XD, et al. Local hyperthermia therapy induces browning of white fat and treats obesity[J]. Cell, 2022, 185(6): 949−966.e19. DOI: 10.1016/j.cell.2022.02.004. [27] Cohade C, Osman M, Pannu HK, et al. Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT[J]. J Nucl Med, 2003, 44(2): 170−176. DOI: 10.1016/S0921-4526(02)01565-X. [28] Becher T, Palanisamy S, Kramer DJ, et al. Brown adipose tissue is associated with cardiometabolic health[J]. Nat Med, 2021, 27(1): 58−65. DOI: 10.1038/s41591-020-1126-7. [29] Pace L, Nicolai E, Basso L, et al. Brown adipose tissue in breast cancer evaluated by[18F] FDG-PET/CT[J]. Mol Imaging Biol, 2020, 22(4): 1111−1115. DOI: 10.1007/s11307-020-01482-z. [30] Wei G, Sun HL, Dong K, et al. The thermogenic activity of adjacent adipocytes fuels the progression of ccRCC and compromises anti-tumor therapeutic efficacy[J]. Cell Metab, 2021, 33(10): 2021−2039.e8. DOI: 10.1016/j.cmet.2021.08.012. [31] Herz CT, Kulterer OC, Prager M, et al. Active brown adipose tissue is associated with a healthier metabolic phenotype in obesity[J]. Diabetes, 2022, 71(1): 93−103. DOI: 10.2337/db21-0475. [32] Halpern BS, Dahlbom M, Auerbach MA, et al. Optimizing imaging protocols for overweight and obese patients: a lutetium orthosilicate PET/CT study[J]. J Nucl Med, 2005, 46(4): 603−607. [33] Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction[J]. Radiology, 1993, 189(3): 847−850. DOI: 10.1148/radiology.189.3.8234714. [34] Sugawara Y, Zasadny KR, Neuhoff AW, et al. Reevaluation of the standardized uptake value for FDG: variations with body weight and methods for correction[J]. Radiology, 1999, 213(2): 521−525. DOI: 10.1148/radiology.213.2.r99nv37521. [35] Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors[J]. J Nucl Med, 2009, 50 (Suppl 1): S122−150. DOI: 10.2967/jnumed.108.057307. -
点击查看大图
计量
- 文章访问数: 4869
- HTML全文浏览量: 3507
- PDF下载量: 27
下载: