Relationship between serum ß-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD
| العنوان: | Relationship between serum ß-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD |
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| المؤلفون: | Grace Shryack, Mary Moore, Grace Meers, Nicole Wieschhaus, Isabella Alessi, Sarah Johnson, Andrew Wheeler, Jamal Ibdah, Elizabeth Parks, Scott Rector |
| المصدر: | Physiology. 38 |
| بيانات النشر: | American Physiological Society, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Physiology |
| الوصف: | Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, is characterized by the presence of excess lipid (>5%) accumulation which can progress to lobular inflammation (NASH), ballooning, and fibrosis. Lipid breakdown, or mitochondrial fatty acid oxidation (FAO), typically leads to two disparate pathways, ketogenesis or the tricarboxylic acid cycle. In a healthy state, FAO and ketogenesis occur proportionally. Additionally, serum ketones levels, specifically ß-hydroxybutyrate (ß-HB), are often utilized as a surrogate marker for hepatic FAO; yet, whether this relationship exists under conditions of NAFLD is not clearly established. Here, we compared fasting serum ketone levels with direct measurement of mitochondrial palmitate (long chain fatty acid) oxidation from liver biopsies obtained from patients undergoing bariatric surgery stratified based on liver disease severity (n=100). NAFLD progression to NASH was associated with reductions in liver HMGCS2 content and gene expression (P < 0.05) (the rate limiting enzyme in ketosis), while this was not accompanied by differences in serum β-HB (P > 0.05). Worsening liver mitochondrial complete palmitate oxidation corresponded with lower liver Hmgcs2 gene expression (r = 0.30, P = 0.01) but not incomplete or total (complete + incomplete) palmitate oxidation (P > 0.05). Likewise, serum β-HB did not correspond with incomplete, complete, or total palmitate oxidation (P > 0.05). Interestingly, we found that liver Hmgcs2 gene expression and serum β-HB significantly correlated with liver mitochondrial β-HAD activity (r = 0.35, P = 0.007) (r = 0.26, P = 0.04) and the mitochondrial fatty acid transporter CPT1a mRNA (r = 0.50, P < 0.0001) (r = 0.42, P < 0.0001) These results suggest that regulators of ketogenesis may meditate markers in mitochondrial FAO, but serum ß-HB may not a suitable measure of FAO in the context of NAFLD. This work was supported by an NIH R01 DK113701-01 (R.S.R., E.J.P., J.A.I) and was partially supported by VA-Merit Grant I01BX003271-01 (R.S.R.). This work was supported with resources and the use of facilities at the University of Missouri and Harry S. Truman Memorial Veterans Hospital in Columbia, Missouri. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| تدمد: | 1548-9221 1548-9213 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::e50dd36fb61ee1ab2cc1590f8d82a5b3Test https://doi.org/10.1152/physiol.2023.38.s1.5731326Test |
| رقم الانضمام: | edsair.doi...........e50dd36fb61ee1ab2cc1590f8d82a5b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15489221 15489213 |
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