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Distinct functions of Ulk1 and Ulk2 in the regulation of lipid metabolism in adipocytes.
Ro, Seung-Hyun,Jung, Chang Hwa,Hahn, Wendy S,Xu, Xin,Kim, Young-Mi,Yun, Young Sung,Park, Ji-Man,Kim, Kwan Hyun,Seo, Minchul,Ha, Tae-Youl,Arriaga, Edgar A,Bernlohr, David A,Kim, Do-Hyung Landes Bioscience 2013 Autophagy Vol.9 No.12
<P>ULK1 (unc-51 like kinase 1) is a serine/threonine protein kinase that plays a key role in regulating the induction of autophagy. Recent studies using autophagy-defective mouse models, such as atg5- or atg7-deficient mice, revealed an important function of autophagy in adipocyte differentiation. Suppression of adipogenesis in autophagy-defective conditions has made it difficult to study the roles of autophagy in metabolism of differentiated adipocytes. In this study, we established autophagy defective-differentiated 3T3-L1 adipocytes, and investigated the roles of Ulk1 and its close homolog Ulk2 in lipid and glucose metabolism using the established adipocytes. Through knockdown approaches, we determined that Ulk1 and Ulk2 are important for basal and MTORC1 inhibition-induced autophagy, basal lipolysis, and mitochondrial respiration. However, unlike other autophagy genes (Atg5, Atg13, Rb1cc1/Fip200, and Becn1) Ulk1 was dispensable for adipogenesis without affecting the expression of CCAAT/enhancer binding protein ? (CEBPA) and peroxisome proliferation-activated receptor gamma (PPARG). Ulk1 knockdown reduced fatty acid oxidation and enhanced fatty acid uptake, the metabolic changes that could contribute to adipogenesis, whereas Ulk2 knockdown had opposing effects. We also found that the expression levels of insulin receptor (INSR), insulin receptor substrate 1 (IRS1), and glucose transporter 4 (SLC2A4/GLUT4) were increased in Ulk1-silenced adipocytes, which was accompanied by upregulation of insulin-stimulated glucose uptake. These results suggest that ULK1, albeit its important autophagic role, regulates lipid metabolism and glucose uptake in adipocytes distinctly from other autophagy proteins.</P>
( Sung Eun Kim ),( Kuk‑ro Yun ),( Jae Min Lee ),( Myung Chul Lee ),( Hyuk‑soo Han ) 대한슬관절학회 2024 대한슬관절학회지 Vol.36 No.-
Background The optimal alignment target for unicompartmental knee arthroplasty (UKA) remains controversial, and literature suggests that its impact on patient-reported outcome measures (PROMs) varies. The purpose of this study was to identify the relationship between changes in the coronal plane alignment of the knee (CPAK) and PROMs in patients who underwent UKA. Methods A retrospective analysis of 164 patients who underwent UKA was conducted. The types of CPAK types categorized into unchanged, minor (shift to an adjacent CPAK type, e.g., type I to II or type I to IV), and major changes (transitioning to a nearby diagonal CPAK type or two types across, such as type I to V or type I to III). PROMs were assessed preoperatively and 1 year postoperatively using the Hospital for Special Surgery (HSS) scores, Knee Society (KS) scores, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Forgotten Joint Scores (FJS). Comparison was performed between patients who experienced and who did not experience any changes in the CPAK. Results Patients with preserved native CPAK alignment demonstrated significantly superior 1 year postoperative outcomes, with higher HSS, KS knee, and WOMAC pain scores (p = 0.042, p = 0.009, and p = 0.048, respectively). Meanwhile, the degree of change in CPAK did not significantly influence the PROMs, and patients who experienced minor and major changes in the CPAK showed comparable outcomes. Conclusion Preserving the native CPAK in UKA procedures is important for achieving favorable clinical outcomes at 1 year postoperative. The extent of change in the CPAK type exerted a limited impact on PROMs, thus emphasizing the importance of change in alignment itself.