👤 Yuji Utsunomiya

We report the case of a 47-year-old woman with severe hypertriglyceridemia due to a homozygous APOA5 c.553G>T (p.Gly185Cys) mutation. She presented with markedly elevated triglyceride levels (TG, 1,047 mg/dL) that were unresponsive to lifestyle modifications. Lipoprotein fractionation revealed increased chylomicrons (CMs, 21%) and very-low-density lipoprotein (35%), consistent with type V hyperlipoproteinemia. Secondary causes, such as diabetes, alcohol intake, and hypothyroidism, were excluded. The post-heparinization lipoprotein lipase (PH-LPL) level was reduced (104 ng/mL), indicating impaired lipolysis. Genetic testing revealed no pathogenic variants in LPL or other major genes related to triglyceride metabolism. A homozygous APOA5 c.553G>T variant was identified. Pemafibrate (0.2 mg/day), a selective PPARα modulator (SPPARMα), was initiated. After 2 months, the blood lipid levels had markedly improved, with the complete disappearance of CMs, and the PH-LPL level had normalized to 173 ng/mL. This case highlights the potential pathogenic role of APOA5 mutations in LPL-related hypertriglyceridemia. Furthermore, it demonstrates the multifaceted therapeutic effects of pemafibrate, suggesting a potential role for SPPARMα therapy in the management of hereditary hypertriglyceridemia. Homozygous APOA5 mutations can cause reduced LPL protein levels, leading to severe hypertriglyceridemia with elevated CMs and VLDL. Pemafibrate may improve both LPL levels and lipid profiles, even in cases with reduced LPL protein and chylomicronemia. ApoA5-related chylomicronemia can resemble familial chylomicronemia syndrome but may respond to therapies such as pemafibrate, highlighting the importance of accurate genetic diagnosis. Show less

Palmitic acid is an important risk factor for the pathogenesis of non-alcoholic steatohepatitis (NASH), but changes in palmitic acid intestinal absorption in NASH are unclear. The aim of this study was to clarify changes in palmitic acid intestinal absorption and their association with the pathogenesis of NASH. A total of 106 participants were recruited to the study, of whom 33 were control subjects (control group), 32 were patients with NASH Brunt stage 1-2 [early NASH (e-NASH)], and 41 were patients with NASH Brunt stage 3-4 [advanced NASH (a-NASH)]. Overall, Significantly upregulated palmitic acid absorption by activation of its transporters was evident in patients with NASH, and clinical progression of NASH was related to palmitic acid absorption. These dietary changes are associated with the onset and progression of NASH. Show less