Key result
Homozygous lpl-a deletion reduces body weight and muscle lipid accumulation under high-fat diet conditions.
Why the study?
Lipoprotein lipase regulates tissue lipid partitioning, but its specific role in fish muscle lipid metabolism remained unclear.
Does lpl-a deletion alter muscle lipid metabolism and reduce high-fat diet-induced lipid accumulation in female zebrafish?
Does lpl-a deletion alter muscle lipid metabolism and reduce high-fat diet-induced lipid accumulation in female zebrafish?
In zebrafish, lpl-a deletion prevents high-fat diet-induced muscle lipid accumulation by shifting muscle metabolism from lipid storage toward oxidative mobilization, though creating an oxidative bottleneck and inflammatory energy stress.
Answers are grounded in this paper and cite their sources.
lpl-a deletion limits muscle lipid storage in zebrafish; leaves open its relevance to human metabolic disease and requires mammalian validation.
Lipoprotein lipase (LPL) regulates tissue lipid partitioning, but its role in fish muscle lipid metabolism remains unclear. Here, a homozygous lpl-a knockout zebrafish line (lpl-a−/−) was constructed using CRISPR/Cas9 and fed a high-fat diet (HFD) for 8 weeks. Muscle physiology, biochemistry, transcriptomics, and metabolomics were analyzed in female zebrafish. Muscle lpl-a expression and LPL content were significantly lower in knockout (KO) than wild-type (WT) fish. After HFD, WT fish showed significantly higher body weight, muscle TG and T-CHO contents, and abdominal fat than WT_LF, whereas KO_HF fish had significantly lower body weight than WT_HF, with muscle TG and T-CHO comparable to KO_LF. Multi-omics revealed reduced G3P and downregulated glycogen synthesis genes, consistent with storage limitation; upregulated acsl5 and downregulated acot15/acot17, consistent with enhanced fatty acid (FA) mobilization toward β-oxidation; downregulated ppara and pgc-1α, accumulated long-chain acylcarnitines, and decreased TCA intermediates, consistent with an oxidative bottleneck; and elevated AMP, increased AMPK protein content, accumulated DAG, increased PKC protein content, decreased SOD activity, and upregulated TLR/NF-κB inflammatory genes, consistent with energy stress and inflammation. Thus, lpl-a deletion reshapes muscle lipid metabolism from a storage-dominant mode toward storage limitation, oxidative mobilization, oxidative bottleneck, and energy stress with inflammation, and is associated with reduced HFD-induced lipid accumulation. lpl-a is a key node determining lipid storage versus oxidation, offering a potential target for improving fish muscle quality.
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Liu et al. (2026) studied Muscle lipid metabolism under high-fat diet. Homozygous lpl-a knockout (lpl-a-/-) with high-fat diet vs. Wild-type (WT) zebrafish fed a high-fat or low-fat diet was evaluated on Body weight, muscle triglyceride (TG) and total cholesterol (T-CHO) contents, and multi-omics muscle lipid metabolism profile. Homozygous lpl-a deletion in female zebrafish fed a high-fat diet for 8 weeks reduced body weight and muscle TG and T-CHO accumulation compared with wild-type fish, reshaping muscle lipid metabolism.
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