肥胖症和非酒精性脂肪肝患者血清β-羟丁酸与肝脏脂肪酸氧化之间的关系

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Mary P Moore, Grace Shryack, Isabella Alessi, Nicole Wieschhaus, Grace M Meers, Sarah A Johnson, Andrew A Wheeler, Jamal A Ibdah, Elizabeth J Parks, R Scott Rector
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引用次数: 0

摘要

非酒精性脂肪肝(NAFLD)的特点是脂质过度积累,并可发展为炎症(NASH)和纤维化。血清β-羟丁酸(β-HB)是生酮途径的产物,通常被用作肝脏脂肪酸氧化(FAO)的替代标志物。然而,这种关系在人类非酒精性脂肪肝中是否成立仍不确定。我们比较了空腹血清(β-HB)水平和肝线粒体棕榈酸酯氧化的直接测量值,并根据非酒精性脂肪肝的严重程度进行了分层(n = 142)。根据非酒精性脂肪肝活动评分(NAS)对患者进行分层:NAS=0(无病)、NAS=1-2(轻度)、NAS=3-4(中度)和NAS³5(晚期)。与无疾病相比,中度和晚期非酒精性脂肪肝与肝脏 HMGCS2 和血清 β-HB 的减少有关,但与 HMGCL mRNA 的减少无关。肝脏线粒体棕榈酸酯完全氧化的恶化与较低的 HMGCS2 mRNA 相对应,但与棕榈酸酯总(完全+不完全)氧化无关。有趣的是,我们发现肝脏 HMGCS2 mRNA 和血清 β-HB 与肝脏线粒体 β-HAD 活性和 CPT1A mRNA 相关。此外,较低的线粒体质量和线粒体周转标志物与肝脏中较低的 HMGCS2 呈正相关。这些数据表明,非酒精性脂肪肝患者肝脏的酮体生成和FAO发生率相当。我们的研究结果支持将血清β-HB作为非酒精性脂肪肝肝损伤和肝FAO的标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Relationship between serum β-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum β-hydroxybutyrate (β-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum β-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum β-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum β-HB correlated with liver mitochondrial β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum β-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum β-hydroxybutyrate (β-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating β-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum β-HB. Our work supports serum β-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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