当前位置:首页 期刊杂志

身体成分与非酒精性脂肪性肝病相关性研究进展

时间:2024-09-03

刘 燕,张 霞

重庆医科大学附属第二医院消化内科,重庆 400010

身体成分与非酒精性脂肪性肝病相关性研究进展

刘 燕,张 霞

重庆医科大学附属第二医院消化内科,重庆 400010

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)发病率逐年上升,其易并发多种代谢性疾病。身体成分包括脂肪成分和非脂成分,与NAFLD关系密切,其相关指标有助于预测NAFLD发病及进展。本文对身体成分与NAFLD相关性作一概述,以期通过改善身体成分作为预防和治疗NAFLD的方式之一。

身体成分;非酒精性脂肪性肝病

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种与胰岛素抵抗(insulin resistance,IR)及炎症反应相关的代谢性疾病。身体成分与NAFLD的发生、发展及并发症的发生关系密切相关。现就身体成分与NAFLD间的关联及其临床应用的研究进展作一概述。

1 身体成分

身体成分指身体各组织的总成分,包括脂肪成分和非脂成分及其分布。前者总称体脂,后者称瘦体质量,瘦体质量包括肌肉、骨骼、皮肤、血液、内脏器官等。体脂含量占体质量百分比称体脂率。

身体成分有诸多测量方法。其中人体测量法可用于预测脂肪量及分布,包括体质量、体质量指数(body mass index,BMI)、皮褶厚度、腰围、臀围、大腿围、腰臀比、腰身比等[1]。双能X线法、水下称重法、生物电阻抗法可用于评估体脂含量、瘦体质量及体脂率[2]。超声、CT及磁共振成像(MRI)可用于评估区域脂肪分布[3],如皮下及内脏脂肪。

2 身体成分与NAFLD

NAFLD发病机制复杂,“二次打击”学说占主要地位。初次打击主要指IR和脂质代谢紊乱所致的肝细胞脂质沉积,再次打击是氧化应激及脂质过氧化反应。同时,细胞因子与炎症反应既参与初次打击脂肪肝形成,也参与再次打击中肝纤维化的启动与进展。而身体成分被证实与IR及炎症反应关系密切。

2.1 瘦体质量 Barsalani等[4]发现瘦体质量减少可增强绝经期妇女炎症反应,独立地引起高敏C反应蛋白升高。另Fornari等[5]研究显示瘦体质量较高者表现为较低的稳态模型胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR),即瘦体质量与IR呈负相关,即瘦体质量低者易发NAFLD,甚至增加死亡率。但Linder等[6]研究显示在青少年男性中瘦体质量较高者IR亦较强,女性则不然。这与男性随年龄变化的睾酮相关,其既能增加身高和肌肉量,也能增加血清胰岛素及HOMA-IR。然而,成人瘦体质量则主要与锻炼引起的骨骼肌增加相关。故瘦体质量与IR甚至NAFLD的相关性受年龄及性别影响。

2.2 体脂重 脂肪分布包括外周脂肪与腹部脂肪,腹部脂肪又含皮下脂肪与内脏脂肪。Ayonrinde等[7]发现脂肪分布男女有异,男性有较高内脏脂肪而女性则有较高皮下脂肪。体脂及脂肪分布在NAFLD发生、发展中起重要作用,同时或存在性别差异。

2.2.1 总脂:高BMI、高脂肪量及高体脂率与NAFLD明显相关[3]。然而Saida等[8]纳入1 851名男性和1 259名女性研究发现,BMI和体脂率的交互作用对NAFLD的影响只存在于男性,而非女性。同时他们发现无论性别,年龄>20岁者体质量增加超过10 kg与脂肪肝明显相关。IR、炎症反应、高脂血症、高胰岛素血症与BMI密切相关[1],意味着高脂肪量者易发生代谢综合征(metabolic syndrome,MS)、2型糖尿病(type 2 diabetes mellitus,T2DM)及心血管疾病(cardiovascular disease,CVD)。因此有学者[9]认为BMI可作为体脂量及体脂率的代表,预测脂肪肝的进展及其并发症的发生。但这个理论是否存在性别差异有待进一步研究。

2.2.2 外周脂肪:Jun等[10]指出在女性中大腿脂肪减少为NAFLD独立危险因素,而在男性中则未表现。同时无论男女,大腿脂肪均与许多代谢危险因素呈负相关,包括HOMA-IR、甘油三酯、谷丙转氨酶(alanine transaminase,ALT)和载脂蛋白B。类似地,有研究[11]报道外周脂肪对脂肪肝起保护作用。但缺乏更多关于性别差异的证据。Cheung等[12]在2007年报道了在成人中颈背部脂肪与炎症反应及肝纤维化相关,加重NAFLD进展。但此结论缺乏近期的研究。

2.2.3 皮下脂肪:目前关于皮下脂肪对NAFLD的发生、发展起抑制或促进作用尚存争议。Gealekman等[13]认为健康皮下脂肪组织对脂肪肝起保护作用,因为脂肪形成需要血管,皮下脂肪组织比内脏脂肪有更好的储脂作用及促进血管生成的能力,可减少内脏脂肪。另Borel等[14]发现皮下脂肪可以分泌脂联素及促进β细胞释放胰岛素,减轻IR。但随着皮下脂肪聚集增多超负荷,其功能异常导致血管生成能力及储脂能力下降,更多的脂肪转移至内脏,这个过程涉及到基因表达、IR、炎症反应及脂肪压力[13-15]。因此,健康的皮下脂肪对NAFLD发生、发展及T2DM等并发症出现具有保护作用,而受损的皮下脂肪则起相反作用。尚需进一步研究探索皮下脂肪健康与受损之间的界限。

2.2.4 内脏脂肪:研究[11]表明,包括肝脏、肠系膜、网膜在内的内脏脂肪与NAFLD的发生及恶化相关,如非酒精性脂肪性肝炎(NASH)及肝纤维化。同时它是NAFLD患者发生T2DM及CVD的重要危险因素[14]。另外,内脏脂肪被证实与ALT相关[11],其为NAFLD中的一种早期生物学指标[16]。在健康人中内脏脂肪为NAFLD临床发作前的表现,能预测其发生。某研究[17]在获取患者肝病理的基础上发现,在无MS及T2DM的非肥胖者中,内脏脂肪亦与各种程度NAFLD相关,其预测价值优于BMI及皮下脂肪。Ayonrinde等[7]发现相同腰围下男性比女性有更多内脏脂肪,正符合了男性脂肪肝患者进展更迅速的现象。然而,Fracanzani等[18]研究显示内脏脂肪影响MS及NAFLD的发生率及临床表现,但并不影响肝损伤的严重程度及NASH肝纤维化的发生。

此外,研究[19]发现增加的心外膜脂肪与BMI、腰围呈正相关,同时在校正腹部脂肪等传统指标后发现其与NAFLD独立相关。这表明心外膜脂肪影响腹部脂肪代谢,其中涉及到系统性IR、血管及免疫细胞的炎症反应。

内脏脂肪与代谢性疾病相关性涉及到诸多机制。首先,内脏脂肪相关的促炎基因转录作为先决条件使CD11c+CD206+和CCR2+的巨噬细胞膨胀,分泌促炎因子[20]。增加的趋化因子及脂肪因子包括白介素6、白介素8、肿瘤坏死因子、抵抗素,而抗炎因子(脂联素、瘦素、白介素10)则降低[21]。而这些因子将影响炎症反应、氧化代谢、能量消耗、内皮功能及脂肪分布[22],从而影响NAFLD及其他代谢疾病。其次,研究[23]发现腹部脂肪与系统性IR相关,独立于年龄、性别,因细胞脂质沉积破坏胰岛素信号转导途径。NAFLD及MS则为系统性IR的产物。另外,内脏脂肪相邻解剖结构引起相关血管及代谢疾病,如肝内脂肪代谢物可通过肝内血管肝内传播,肠系膜、大网膜等处代谢产物可通过门静脉系统入肝而造成肝损伤[24]。

3 身体成分在NAFLD中的应用

3.1 疾病预测 既然身体成分与代谢性疾病发生、发展、转归密切相关,这对临床预测、预防、治疗疾病有指导意义。研究[1]发现,BMI、腰围、腰身比与体脂量及体脂率相关,而体脂量和体脂率与NAFLD相关。相较内脏脂肪,腰围、腰身比与皮下脂肪关联更密切,而躯干四肢脂肪比、腰臀比则与内脏脂肪关联最密切[25]。因此,BMI、腰围、腰身比、腰臀比可作为普筛项目来预测NAFLD。Monteiro等[3]认为腰围作为一个特异性高于敏感性的指标,在儿童和成人中对NAFLD均有高预测价值。Kim等[26]发现在韩国男性中脂肪指数联合腰身比相较其他指标对代谢因素有最佳预测效果。而体脂率及体脂分布尤其内脏脂肪更与NAFLD和MS相关,预测价值高。因此,人们可及时监测身体成分相关指标,其异常结果有助于医者在看似正常人群中预测和预防NAFLD发生,同时在疾病期有针对地减肥治疗,避免严重并发症的发生。

3.2 综合治疗 长期饮食调节(包括减少反式脂肪酸、果糖和增加多不饱和脂肪酸)可降低BMI,减少脂肪量、皮下及内脏脂肪,进而改善NAFLD患者肝功能[27]。此外,有氧运动尤其抗阻训练可减少总脂肪量、躯干脂肪和增加瘦体质量,从而改善炎症反应、IR及肝纤维化[28]。近期Meta分析[29]展现了减肥手术治疗病态肥胖合并NAFLD的优越性,其可使BMI平均下降15.13,腹部脂肪亦有不同程度下降。其可改善IR及慢性炎症,表现为不加重各阶段肝纤维化,同时降低肝脂肪变性、肝气球样变、小叶炎症及HOMA-IR。但关于手术远期副反应报道少,且在肝硬化患者中有效性及安全性尚不明确,需大样本研究及长期随访。Marchesini等[30]对手术者(十二指肠转位术、胆胰分流术、胃旁路术、胃束带术、袖状胃减容术)随访12个月,用BAROS评估生活质量、体质量减轻量、临床条件、并发症、再手术率等,发现十二指肠转位术评分最高。关于减肥药物,研究[31]认为脂肪因子类的胰淀素受体激动剂(普兰林肽)和瘦素类似物(曲美普汀)均能减少体脂及内脏脂肪,但副作用较大。而纳洛酮和丁胺苯丙酮融合的缓释剂(纳曲酮)、选择性5羟色胺受体激动剂(氯卡色林)、GLP-1受体(利拉鲁肽)及脂肪酶抑制剂(奥利司他)均能降低脂肪,但缺乏远期不良反应观察。总之,生活方式干预联合减重手术可改善患者身体成分,最终改善NAFLD等代谢病。

总脂及脂肪分布与NAFLD发生发展转归及其并发症的出现明显相关,人体测量学指标有助于预测NAFLD发病及进展风险,并通过改善身体成分的综合治疗可达到预防和治疗疾病的目的。但仍待进一步研究明确何种指标对NAFLD预测效果最佳,是否存在年龄及性别差异,及针对改善生活方式无效者如何通过更安全有效的药物减少腹部脂肪以改善NAFLD。

[1]Barreira TV,Staiano AE,Harrington DM,et al. Anthropometric correlates of total body fat,abdominal adiposity,and cardiovascular disease risk factors in a biracial sample of men and women [J]. Mayo Clin Proc,2012,87(5): 452-460.

[2]Hillier SE,Beck L,Petropoulou A,et al. A comparison of body composition measurement techniques [J]. J Hum Nutr Diet,2014,27(6): 626-631.

[3]Monteiro PA,Antunes Bde M,Silveira LS,et al. Body composition variables as predictors of NAFLD by ultrasound in obese children and adolescents [J]. BMC Pediatr,2014,14: 25.

[4]Barsalani R,Riesco É,Perreault K,et al. Variation in C-reactive protein following weight loss in obese insulin resistant postmenopausal women: is there an independent contribution of lean body mass? [J]. Exp Clin Endocrinol Diabetes,2015,123(3): 198-203.

[5]Fornari R,Francomano D,Greco EA,et al. Lean mass in obese adult subjects correlates with higher levels of vitamin D,insulin sensitivity and lower inflammation [J]. J Endocrinol Invest,2015,38(3): 367-372.

[6]Linder K,Springer F,Machann J,et al. Relationships of body composition and liver fat content with insulin resistance in obesity-matched adolescents and adults [J]. Obesity (Silver Spring),2014,22(5): 1325-1331.

[7]Ayonrinde OT,Olynyk JK,Beilin LJ,et al. Gender-specific differences in adipose distribution and adipocytokines influence adolescent nonalcoholic fatty liver disease [J]. Hepatology,2011,53(3): 800-809.

[8]Saida T,Fukushima W,Ohfuji S,et al. Effect modification of body mass index and body fat percentage on fatty liver disease in a Japanese population [J]. J Gastroenterol Hepatol,2014,29(1): 128-136.

[9]Mager DR,Yap J,Rodriguez-Dimitrescu C,et al. Anthropometric measures of visceral and subcutaneous fat are important in the determination of metabolic dysregulation in boys and girls at risk for nonalcoholic fatty liver disease [J]. Nutr Clin Pract,2013,28(1): 101-111.

[10]Jun DW,Han JH,Kim SH,et al. Association between low thigh fat and non-alcoholic fatty liver disease [J]. J Gastroenterol Hepatol,2008,23(6): 888-893.

[11]Paniagua JA,Escandell-Morales JM,Gil-Contreras D,et al. Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: role of nutrition and insulin challenge [J]. Nutrition,2014,30(2): 177-185.

[12]Cheung O,Kapoor A,Puri P,et al. The impact of fat distribution on the severity of nonalcoholic fatty liver disease and metabolic syndrome [J]. Hepatology,2007,46(4): 1091-1100.

[13]Gealekman O,Guseva N,Hartigan C,et al. Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity [J]. Circulation,2011,123(2): 186-194.

[14]Borel AL,Nazare JA,Smith J,et al. Visceral,subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance,impaired fasting glucose and/or impaired glucose tolerance [J]. Int J Obes (Lond),2015,39(3): 495-501.

[15] Lê KA,Mahurkar S,Alderete TL,et al. Subcutaneous adipose tissue macrophage infiltration is associated with hepatic and visceral fat deposition,hyperinsulinemia,and stimulation of NF-κB stress pathway [J]. Diabetes,2011,60(11): 2802-2809.

[16]Verma S,Jensen D,Hart J,et al. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) [J]. Liver Int,2013,33(9): 1398-1405.

[17]Ha Y,Seo N,Shim JH,et al. Intimate association of visceral obesity with non-alcoholic fatty liver disease in healthy Asians: a case-control study [J]. J Gastroenterol Hepatol,2015,30(11): 1666-1672.

[18]Fracanzani AL,Valenti L,Bugianesi E,et al. Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity [J]. J Hepatol,2011,54(6): 1244-1249.

[19]Lai YH,Yun CH,Yang FS,et al. Epicardial adipose tissue relating to anthropometrics,metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography [J]. J Am Soc Echocardiogr,2012,25(2): 234-241.

[20]du Plessis J,van Pelt J,Korf H,et al. Association of adipose tissue inflammation with histological severity of nonalcoholic fatty liver disease [J]. Gastroenterology,2015,149(3): 635-648,e14.

[21]Campos RM,de Piano A,da Silva PL,et al. The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy [J]. Endocrine,2012,42(1): 146-156.

[22]Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases [J]. Best Pract Res Clin Endocrinol Metab,2013,27(2): 163-177.

[23]Kato K,Takamura T,Takeshita Y,et al. Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease [J]. PLoS One,2014,9(3): e92170.

[24]Blüher M. Clinical relevance of adipokines [J]. Diabetes Metab J,2012,36(5): 317-327.

[25]Savgan-Gurol E,Bredella M,Russell M,et al. Waist to hip ratio and trunk to extremity fat (DXA) are better surrogates for IMCL and for visceral fat respectively than for subcutaneous fat in adolescent girls [J]. Nutr Metab (Lond),2010,7: 86.

[26]Kim JY,Oh S,Chang MR,et al. Comparability and utility of body composition measurement vs. anthropometric measurement for assessing obesity related health risks in Korean men [J]. Int J Clin Pract,2013,67(1): 73-80.

[28]Bacchi E,Negri C,Targher G,et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial) [J]. Hepatology,2013,58(4): 1287-1295.

[29]Bower G,Toma T,Harling L,et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology [J]. Obes Surg,2015,25(12): 2280-2289.

[30]Marchesini JB,Nicareta JR. Comparative study of five different surgical techniques for the treatment of morbid obesity using BAROS [J]. Arq Bras Cir Dig,2014,27 Suppl 1: 17-20.

[31]Barja-Fernandez S,Leis R,Casanueva FF,et al. Drug development strategies for the treatment of obesity: how to ensure efficacy,safety,and sustainable weight loss [J]. Drug Des Devel Ther,2014,8: 2391-2400.

(责任编辑:王全楚)

Progress of the correlation between body composition and non-alcoholic fatty liver disease

LIU Yan,ZHANG Xia

Department of Gastroenterology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year,which can develop into multiple metabolic diseases. Body composition,containing fat mass and lean mass,is closely related with NAFLD. Some correlative indicators can be used to predict risk and progress of NAFLD. This article will summarize the correlation between body composition and NAFLD,aiming to prevent and treat NAFLD through improving body composition.

Body composition; Non-alcoholic fatty liver disease

刘燕,在读硕士研究生,研究方向:肝病。E-mail:jianjian200909@163.com

张霞,博士,教授,主任医师,研究方向:肝病与代谢综合征。E-mail:sunnyzhangx@gmail.com

10.3969/j.issn.1006-5709.2016.04.004

R575.5

A

1006-5709(2016)04-0375-03

2015-07-11

免责声明

我们致力于保护作者版权,注重分享,被刊用文章因无法核实真实出处,未能及时与作者取得联系,或有版权异议的,请联系管理员,我们会立即处理! 部分文章是来自各大过期杂志,内容仅供学习参考,不准确地方联系删除处理!