Effects of ethanol and sex on propionate metabolism evaluated via a faster (13)C-propionate breath test in rats.

Effects of ethanol and sex on propionate metabolism evaluated via a faster (13)C-propionate breath test in rats.
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DOI:
10.3748/wjg.v29.i21.3269
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发表时间:
2023-06-07
影响因子:
4.3
通讯作者:
Urita Y
Urita Y
中科院分区:
医学2区
文献类型:
--
作者:
Sasaki Y;Kawagoe N;Imai T;Urita Y

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酒精中毒被认为是维生素B12(VB 12)缺乏的危险因素。由于VB 12作为甲基丙二酰辅酶A的辅酶,丙酸代谢的关键酶,13 C-丙酸呼气试验(PBT)已被研究作为VB 12缺乏症的非侵入性诊断方式。然而,传统的PBT需要2小时,这在临床实践中是不方便的。我们假设更快的PBT可用于评估丙酸盐代谢,并且更容易适用于临床实践。评价用于评估长期乙醇消耗对乙醇喂养大鼠(ER)丙酸盐代谢影响的更快PBT。通过在F344/DuCrj大鼠后代中用16%乙醇溶液替代标准饮用水(对于对照大鼠,CR)获得ER。通过从口腔到胃插入金属小管,向男性和女性ER和CR给予13 C-丙酸盐水溶液,进行更快的PBT;将呼出气体收集在袋中,通过红外同位素光谱法测量其13 CO2/12 CO2同位素比。分别采用化学发光免疫法和乳酸脱氢酶-紫外法测定血清维生素B12和丙氨酸转氨酶(ALT)水平。我们分别使用正态和非正态分布变量的t检验和Mann-Whitney U检验评价了雄性和雌性之间以及ER和CR之间平均体重、13 CO2变化(Δ 13 CO2 ‰)、峰值Δ 13 CO2 ‰和血清VB 12和ALT的统计学差异。男性体重显著高于女性(P < 0.001); CR体重显著高于ER(P < 0.008)。雌性和雄性动物的Δ 13 CO2分别在20 min和30 min达到峰值(Cmax),20-30 min后下降,所有组均无反弹。在15-45分钟时,雄性动物的Cmax和Δ 13 CO2显著高于雌性动物(P < 0.05;所有配对)。相对于男性CR,男性ER中丙酸盐代谢增强,而女性ER和CR之间的代谢无显著差异。男性血清VB 12水平高于女性,ER组和CR组之间无显著差异。男性CR的ALT水平明显高于男性ER。因此,慢性乙醇消耗可能会通过肠道细菌和肠道微生物组组成的变化引发脂肪酸的产生。更快的PBT表明,16%的乙醇消耗促进丙酸代谢而不诱导肝损伤。该PBT可用于临床评价肠道植物群状态。
Alcoholism is regarded as a risk factor for vitamin B12 (VB12) deficiency. Because VB12 serves as a coenzyme of methylmalonyl-CoA mutase, a key enzyme in propionate metabolism, the 13C-propionate breath test (PBT) has been studied as a non-invasive diagnostic modality for VB12 deficiency. However, the conventional PBT requires 2 h, which is inconvenient in clinical practice. We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice. To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats (ERs). ERs were obtained by replacing standard drinking water (for control rats, CRs) with 16% ethanol solution in descendants of F344/DuCrj rats. Faster PBT was performed by administering 13C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach; exhaled gas was collected in a bag to measure its 13CO2/12CO2 isotope ratio via infrared isotope spectrometry. Serum VB12 and alanine transaminase (ALT) levels were measured via chemiluminescence immunoassay and the lactate dehydrogenase-ultraviolet method, respectively. We evaluated statistical differences in mean body weight, change in 13CO2 (Δ13CO2‰), peak Δ13CO2‰, and serum VB12 and ALT, between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables, respectively. Males weighed significantly more than females (P < 0.001); CRs weighed significantly more than ERs (P < 0.008). Δ13CO2 reached a peak (Cmax) at 20 min and 30 min in females and males, respectively, decreasing after 20-30 min without rebound in all groups. Males had significantly higher Cmax and Δ13CO2 at 15-45 min than females (P < 0.05; for all pairs). Propionate metabolism was enhanced in male ERs relative to male CRs, whereas metabolism did not differ markedly between ERs and CRs for females. Males had higher serum VB12 levels than females, without prominent differences between the ER and CR groups. Male CRs had notably higher ALT levels than male ERs. Thus, chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition. Faster PBT shows that 16% ethanol consumption promotes propionate metabolism without inducing liver injury. This PBT may be used clinically to evaluate gut flora status.
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