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Proteomics of lipid droplet isolated from con and Sec16b knockout livers

ABSTRACT: The liver plays a critical role in lipid homeostasis, where lipids are either secreted as very-low-density lipoproteins (VLDL) or stored in lipid droplets (LDs). However, the regulatory mechanisms governing these two interconnected processes remain poorly understood. Here, we demonstrate that SEC16B is crucial for regulating lipid secretion and storage within the liver. Genome-wide association studies have identified single-nucleotide polymorphisms in SEC16B to be highly associated with serum lipid levels in humans. Hepatic Sec16b deficiency decreases serum lipid levels due to impaired VLDL lipidation and secretion. SEC16B partially localizes at ER-LD contact sites and promotes LD expansion by facilitating the targeting of ER proteins to LDs. More importantly, suppression of Sec16b dramatically lowers serum lipid levels and reduces atherosclerotic lesion size in Ldlr null mice. These data reveal a novel mechanism that coordinates VLDL and LD metabolism and suggest SEC16B as a promising therapeutic target for atherosclerosis treatment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Wei Lu

LAB HEAD: Bo Wang

PROVIDER: PXD056229 | Pride | 2026-04-23

REPOSITORIES: Pride

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