Dawson Alison J, Kilpatrick Eric S, Coady Anne-Marie, Elshewehy Abeer M M, Dakroury Youssra, Ahmed Lina, Atkin Stephen L, Sathyapalan Thozhukat
Department of Diabetes and Endocrinology, University of Hull, Hull, UK.
Department of Clinical Biochemistry, Sidra Medical and Research Centre, Doha, Qatar.
BMC Endocr Disord. 2017 Jul 14;17(1):41. doi: 10.1186/s12902-017-0194-2.
Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile.
Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD).
Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT.
Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD.
ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).
有证据表明，通过大麻素受体1（CB1）激活内源性大麻素系统与肝损伤加重有关，而拮抗CB1可能有益。本研究的目的是确定利莫那班（CB1拮抗剂）对丙氨酸氨基转移酶（ALT，一种肝细胞损伤标志物）及肝脏炎性细胞因子谱的影响。
对2项研究进行事后分析，这2项研究涉及50名患有多囊卵巢综合征（PCOS）且体重匹配良好的肥胖女性，她们被随机分配接受减重治疗；利莫那班（每日20毫克）或奥利司他（每日3次，每次120毫克），或接受胰岛素增敏治疗二甲双胍（每日3次，每次500毫克）或吡格列酮（每日45毫克）。所有受试者均无非酒精性脂肪性肝病（NAFLD）。
接受利莫那班治疗12周可降低ALT水平和体重（p < 0.01），并且ALT变化量与HOMA-IR变化量之间呈负相关（p < 0.001），但ALT变化量与体重变化量之间无相关性。奥利司他可显著降低体重（p < 0.01）；然而，奥利司他、二甲双胍和吡格列酮对ALT均无影响。所有组的游离雄激素指数均下降（p < 0.05）。炎性标志物hs-CRP仅在吡格列酮治疗组中降低（p < 0.001），且与ALT变化无关。各组之间白细胞介素-1β、白细胞介素-6、白细胞介素-7、白细胞介素-10、白细胞介素12、肿瘤坏死因子-α、单核细胞趋化蛋白-1和干扰素-γ的炎性细胞因子谱无差异。所有干预措施对ALT的生物学变异性均无影响。
在无NAFLD的PCOS肥胖女性中，利莫那班通过阻断CB1受体降低血清ALT水平，这一作用独立于体重减轻和肝脏炎性标志物。
ISRCTN58369615（2007年2月；追溯注册）ISRCTN75758249（2007年10月；追溯注册）。
