{'fraction_non_alphanumeric': 0.02608242044861763, 'fraction_numerical': 0.0, 'mean_word_length': 5.3933333333333335, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Mechanism of ATGL mediated changes in hepatic energy metabolism: role of LFABP

Adipose triglyceride lipase (ATGL) catalyzes the rate‐limiting step in triacylglycerol (TAG) hydrolysis in most tissues. We have previously shown that hepatic ATGL preferentially channels hydrolyzed fatty acids (FAs) to β‐oxidation and induces peroxisome proliferator‐activated receptor‐α (PPAR‐α) target gene expression. Nevertheless, the mechanisms that mediate this pathway are still unknown. We hypothesized that a FA carrier such as liver fatty acid binding protein (LFABP), which is known to influence FA oxidation and PPAR‐α, may be involved in transporting FAs from lipid droplets to mitochondria for β‐oxidation or the nucleus for ligand delivery. Thus, we employed the adenovirus‐mediated approach to suppress or overexpress hepatic ATGL expression in wild type (WT) or LFABP knockout (LFABP KO) mice. ATGL knockdown increased liver weight and TAG content and ATGL overexpression decreased liver TAG content to a similar extent in both strains of mice. As expected, the mRNA expression of PPAR‐α and its target genes were upregulated in WT mice injected with adenovirus overexpressing ATGL and decreased in mice treated with ATGL shRNA. Surprisingly, manipulating ATGL expression in LFABP KO mice resulted in nearly identical changes in PPAR‐α and its target genes compared to WT mice suggesting that LFABP is not required to carry FA ligands from ATGL to PPAR‐α. Furthermore, LFABP did not impair the effects of ATGL on TAG hydrolysis or oxidation of hydrolyzed FAs in primary hepatocyte cultures. Taken together, we conclude that LFABP, despite being a major intracellular FA carrier, does not mediate the effects of ATGL on PPAR‐α and is not required to channel ATGL‐hydrolyzed FAs to mitochondria for β‐oxidation. These data point to a more complex mechanism linking ATGL to downstream changes in hepatic energy metabolism.