17β-hydroxysteroid dehydrogenase-13 is a hepatocyte-specific, lipid droplet-associated protein. A common loss-of-function variant ofHSD17B13(rs72613567: TA) protects patients against non-alcoholic fatty liver disease with underlying mechanism incompletely understood. In the present study, we identify the serine 33 of 17β-HSD13 as an evolutionally conserved PKA target site and its phosphorylation facilitates lipolysis by promoting its interaction with ATGL on lipid droplets. Targeted mutation of Ser33 to Ala (S33A) decreases ATGL-dependent lipolysis in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Importantly, a transgenic knock-in mouse strain carrying theHSD17B13S33A mutation (HSD17B13^33A/A) spontaneously develops hepatic steatosis with reduced lipolysis and increased inflammation. Moreover,Hsd17B13^33A/Amice are more susceptible to high-fat diet-induced nonalcoholic steatohepatitis. Finally, we find reproterol, a potential 17β-HSD13 modulator and FDA-approved drug, confers a protection against nonalcoholic steatohepatitis via PKA-mediated Ser33 phosphorylation of 17β-HSD13. Therefore, targeting the Ser33 phosphorylation site could represent a potential approach to treat NASH.

Background/Aims: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration. Methods: 2/3 partial hepatectomy (PH) was performed in wild type C57BL/6J (WT) and Srebp-1c-/- mice. The lipid contents in serum and liver were measured by enzymatic colorimetric methods. Hepatic lipid droplets were detected by Oil Red O staining and immunohistological staining. Hepatic expression of genes involved in lipid metabolism and cellular proliferation was determined by real-time PCR and/or immunoblot. Hepatocyte proliferation and liver regeneration were assessed by BrdU staining and the weight of remanent liver lobes in Srebp-1c-/- mice, respectively. Results: Srebp-1c-/- mice displayed reduced triglyceride and fatty acids but increased cholesterol in the liver before PH. In response to PH, hepatocellular DNA synthesis was elevated and cell cycle progression was prolonged in Srebp-1c-/- mice, which was associated with enhanced liver regeneration. However, Srebp-1c-/- mice had comparable triglyceride and fatty acid contents and expressions of related genes compared with WT mice during the liver regeneration. In contrast, SREBP-1c-deficiency-induced alteration of cholesterol metabolism was retained during the liver regeneration after PH. Srebp-1c-/- mice exhibited higher cholesterol contents and enhanced expression of SREBP-2 and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in the liver than WT mice after PH. Moreover, downregulation of genes involved in cholesterol elimination was observed after PH in Srebp-1c-/- mice. Conclusion: SREBP-1c deficiency in mice did not interfere with triglyceride and fatty acid metabolism but was associated with significant changes in cholesterol profiles during liver regeneration after PH. These results suggest that increased hepatocellular cholesterol storage and cholesterol availability with the enhanced liver regeneration are identified in Srebp-1c-/- mice. This study also shows that providing requisite cholesterol levels to proliferating hepatocytes and keeping appropriate cholesterol metabolism are required for normal liver regeneration.

In recent years, metabolic disorder, especially fatty liver disease, has been considered a major challenge to global health. The attention of researchers focused on expanding knowledge of the regulation mechanism behind these diseases and towards the new diagnostics tools and treatments. The pathophysiology of the fatty liver disease is undoubtedly complex. Abnormal hepatic lipid accumulation is a major symptom of most metabolic diseases. Therefore, the identification of novel regulation factors of lipid metabolism is important and meaningful. As a new diagnostic tool, the function of microRNAs during fatty liver disease has recently come into notice in biological research. Accumulating evidence supports the influence of miRNAs in lipid metabolism. In this review, we discuss the potential role of miRNAs in liver lipid metabolism and the pathogenesis of fatty liver disease.

Diatoms, known as photosynthetic unicellular algae, can produce natural biosilica frustules that exhibit great biocompatibility, superhydrophilicity, and superhemophilicity. In our study, the diatom Navicula australoshetlandica sp. was isolated from aquaculture wastewater and pretreated to obtain frustules so as to explore their hemostasis characteristics. A special “porous web” (6–8 nm) substructure in the ordered nanopores (165–350 nm) of boat-shaped diatom frustule was observed in Navicula australoshetlandica sp. using SEM and TEM analysis. Moreover, X-ray, N₂ adsorption–desorption isotherms, and BET analysis showed that the diatom frustule is a mesoporous material with a surface area of 401.45 m² g⁻¹ amorphous silica. FTIR analysis showed that Navicula australoshetlandica sp. frustules possessed abundant OH functional groups. A low hemolysis ratio was observed for 1–5 mg mL⁻¹ diatom frustules that did not exceed 1.55 ± 0.06%, which indicates favorable hemocompatibility. The diatom frustules exhibited the shortest clotting time (134.99 ± 7.00 s) with a hemostasis material/blood (mg/μL) ratio of 1:100, which is 1.83 times (112.32 s) shorter than that of chitosan. The activated partial thromboplastin time (aPTT) of diatom frustule was also 44.53 s shorter than the control. Our results demonstrate the potential of Navicula australoshetlandica sp. diatom frustules to be used as medical hemostasis material.

Editorial: Lipid droplets and mitochondria in metabolic diseases