Relationship Between Serum β-Hydroxybutyrate and Hepatic Fatty Acid Oxidation in Individuals with Obesity and NAFLD

Am J Physiol Endocrinol Metab. 2024 Feb 21. doi: 10.1152/ajpendo.00336.2023. Online ahead of print.ABSTRACTNAFLD is characterized by excess lipid accumulation which can progress to inflammation (NASH), and fibrosis. Serum β-hydroxybutyrate (β-HB), a product of the ketogenic pathway, is commonly employed 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 NAS³5 (advanced). Moderate and advanced NAFLD associated with reductions in liver HMGCS2, serum β-HB, but not 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-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...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Source Type: research