PMID- 36565788 OWN - NLM STAT- MEDLINE DCOM- 20231117 LR - 20231117 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 562 DP - 2023 Feb 15 TI - Zinc finger protein 251 deficiency impairs glucose metabolism by inducing adipocyte hypertrophy. PG - 111838 LID - S0303-7207(22)00286-6 [pii] LID - 10.1016/j.mce.2022.111838 [doi] AB - Zinc finger protein (ZFP) 251 is a member of the C(2)H(2) ZFP family containing a Kruppel-associated box domain that might mainly act as a transcriptional repressor. However, its cellular function remains largely unknown. Here, we discovered that ZFP251 deficiency caused glucose intolerance in mice. This phenotype was associated with impaired insulin signaling due to hypertrophic changes in white adipose tissue (WAT). Gene ontology analysis revealed that ZFP251 deficiency affected the expression of genes associated with adipocyte differentiation and lipid and fatty acid metabolism. Consistent with in vivo results, hypertrophic changes were observed in Zfp251 knockdown (KD) 3T3-L1 adipocytes. In addition, Zfp251 KD 3T3-L1 preadipocytes exhibited cell cycle arrest in G0/G1 phase, leading to impaired differentiation into mature adipocytes, upon which abnormal mitotic clonal expansion and reduced expression of adipogenic markers were exhibited. These results suggest that ZFP251 deficiency causes impaired adipogenesis and adipocyte hypertrophy, leading to dysfunction of WAT. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Kim, Eunsu AU - Kim E AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Ham, Sun Ah AU - Ham SA AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Hwang, Jung Seok AU - Hwang JS AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Won, Jun Pil AU - Won JP AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Lee, Hyuk Gyoon AU - Lee HG AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Hur, Jinwoo AU - Hur J AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. FAU - Seo, Han Geuk AU - Seo HG AD - College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. Electronic address: hgseo@konkuk.ac.kr. LA - eng PT - Journal Article DEP - 20221221 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - IY9XDZ35W2 (Glucose) RN - 0 (Zfp251 protein, mouse) SB - IM MH - Animals MH - Mice MH - 3T3-L1 Cells MH - *Adipocytes/metabolism MH - *Adipogenesis/genetics MH - Cell Differentiation/genetics MH - Glucose/metabolism MH - Hypertrophy/metabolism MH - Zinc Fingers OTO - NOTNLM OT - Adipocyte hypertrophy OT - Adipogenesis OT - Glucose intolerance OT - Insulin resistance OT - ZFP251 OT - Zinc finger protein COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2022/12/25 06:00 MHDA- 2023/01/25 06:00 CRDT- 2022/12/24 19:13 PHST- 2022/10/24 00:00 [received] PHST- 2022/12/05 00:00 [revised] PHST- 2022/12/20 00:00 [accepted] PHST- 2022/12/25 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2022/12/24 19:13 [entrez] AID - S0303-7207(22)00286-6 [pii] AID - 10.1016/j.mce.2022.111838 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2023 Feb 15;562:111838. doi: 10.1016/j.mce.2022.111838. Epub 2022 Dec 21.