PMID- 35290477 OWN - NLM STAT- MEDLINE DCOM- 20220715 LR - 20231031 IS - 1436-6215 (Electronic) IS - 1436-6207 (Linking) VI - 61 IP - 5 DP - 2022 Aug TI - The daily caloric restriction and alternate-day fasting ameliorated lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1. PG - 2775-2797 LID - 10.1007/s00394-022-02850-x [doi] AB - PURPOSE: A possible link between pescadillo 1 (PES1) and lipid metabolism has been reported. However, whether PES1 is involved in the effects of daily caloric restriction (CR) and alternate-day fasting (ADF) interventions on diabetes-related lipid dysregulation is not elucidated. The current study aims are to explore the role of PES1 in effects of CR and ADF on diabetic mice and related mechanism. METHODS: Eight-week-old male db/db mice with type 2 diabetes mellitus (T2DM) were randomly divided into untreated T2DM, CR and ADF groups. McArdle hepatocytes were treated with 48 h high glucose (HG), 48 h normal glucose (NG) and 24 h HG plus 24 h NG, respectively. Pes1 siRNA and overexpression plasmid were, respectively, transfected into liver cells, and AAV(9)-Pes1-shRNA was injected into db/db mice. RESULTS: After 12-week interventions, the peroxisome proliferator-activated receptor alpha (PPAR-alpha) and carnitine palmitoyltransferase 1A (CPT1A) levels in livers of T2DM mice were enhanced by CR and ADF interventions with reductions of hepatic and plasma triglycerides. Unexpectedly, hepatic PES1 levels were downregulated by two interventions, consistent with the results of 48 h NG and 24 h HG plus 24 h NG-treated cells. Moreover, CPT1A level was upregulated in Pes1-siRNA-treated cells and AAV(9)-Pes1-shRNA injected murine livers, in contrast to Pes1 overexpression in cultured cells. Mechanistically, 48 h NG or 24 h HG plus 24 h NG treatment increased PPAR-alpha binding to Pes1 promoter, suppressing the PES1 expression, thereby lowering the PES1-mediated ubiquitination of CPT1A. CONCLUSION: The present study suggests that CR and ADF may improve lipid dysregulation in diabetic mice by downregulating hepatic PES1. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany. FAU - Zhou, Jielin AU - Zhou J AD - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. FAU - Jiang, Zhengxuan AU - Jiang Z AD - Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230021, Anhui, China. FAU - Lin, Yan AU - Lin Y AD - Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. FAU - Li, Chengcheng AU - Li C AD - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. FAU - Liu, Juan AU - Liu J AD - Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. FAU - Tian, Mengjun AU - Tian M AD - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. FAU - Liu, Yong AU - Liu Y AD - AIER Hefei Eye Hospital Affiliated To Anhui Medical University, Hefei, 230031, Anhui, China. 18971021155@189.cn. FAU - Chen, Keyang AU - Chen K AD - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. chenkeyang@ahmu.edu.cn. AD - Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China. chenkeyang@ahmu.edu.cn. LA - eng GR - 81570786/National Natural Science Foundation of China/ GR - 82070986/National Natural Science Foundation of China/ GR - 9101041203/Wanjiang scholar grants from Anhui Province of China/ PT - Journal Article DEP - 20220315 PL - Germany TA - Eur J Nutr JT - European journal of nutrition JID - 100888704 RN - 0 (Peroxisome Proliferator-Activated Receptors) RN - 0 (RNA, Small Interfering) RN - 0 (Triglycerides) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Caloric Restriction MH - *Diabetes Mellitus, Experimental/metabolism MH - *Diabetes Mellitus, Type 2/metabolism/therapy MH - Fasting/physiology MH - Glucose/metabolism MH - Lipid Metabolism MH - Liver/metabolism MH - Male MH - Mice MH - Peroxisome Proliferator-Activated Receptors/metabolism MH - RNA, Small Interfering/metabolism MH - Triglycerides/metabolism OTO - NOTNLM OT - Alternate-day fasting (ADF) OT - Daily caloric restriction (CR) OT - Glucose metabolism OT - Lipid metabolism OT - Pescadillo 1 (PES1) OT - Type 2 diabetes (T2DM) EDAT- 2022/03/16 06:00 MHDA- 2022/07/16 06:00 CRDT- 2022/03/15 17:19 PHST- 2021/09/24 00:00 [received] PHST- 2022/02/22 00:00 [accepted] PHST- 2022/03/16 06:00 [pubmed] PHST- 2022/07/16 06:00 [medline] PHST- 2022/03/15 17:19 [entrez] AID - 10.1007/s00394-022-02850-x [pii] AID - 10.1007/s00394-022-02850-x [doi] PST - ppublish SO - Eur J Nutr. 2022 Aug;61(5):2775-2797. doi: 10.1007/s00394-022-02850-x. Epub 2022 Mar 15.