PMID- 32275973 OWN - NLM STAT- MEDLINE DCOM- 20200803 LR - 20210602 IS - 1532-8600 (Electronic) IS - 0026-0495 (Print) IS - 0026-0495 (Linking) VI - 107 DP - 2020 Jun TI - Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes. PG - 154225 LID - S0026-0495(20)30089-5 [pii] LID - 10.1016/j.metabol.2020.154225 [doi] AB - BACKGROUND: Caloric restriction (CR) delays the onset of metabolic and age-related disorders. Recent studies have demonstrated that formation of beige adipocytes induced by CR is strongly associated with extracellular remodeling in adipose tissue, decrease in adipose tissue inflammation, and improved systemic metabolic homeostasis. However, beige adipocytes rapidly transition to white upon CR withdrawal through unclear mechanisms. MATERIALS AND METHODS: Six-week old C57BL6 mice were fed with 40% CR chow diet for 6 weeks. Subsequently, one group of mice was switched back to ad libitum chow diet, which was continued for additional 2 weeks. Adipose tissues were assessed histologically and biochemically for beige adipocytes. RESULTS: Beige adipocytes induced by CR rapidly transition to white adipocytes when CR is withdrawn independent of parkin-mediated mitophagy. We demonstrate that the involution of mitochondria during CR withdrawal is strongly linked with a decrease in mitochondrial biogenesis. We further demonstrate that beige-to-white fat transition upon beta3-AR agonist-withdrawal could be attenuated by CR, partly via maintenance of mitochondrial biogenesis. CONCLUSION: In the model of CR, our study highlights the dominant role of mitochondrial biogenesis in the maintenance of beige adipocytes. We propose that loss of beige adipocytes upon beta3-AR agonist withdrawal could be attenuated by CR. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Mooli, Raja Gopal Reddy AU - Mooli RGR AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Mukhi, Dhanunjay AU - Mukhi D AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Watt, Mikayla AU - Watt M AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Edmunds, Lia AU - Edmunds L AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Xie, Bingxian AU - Xie B AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Capooci, Joseph AU - Capooci J AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Reslink, Matthew AU - Reslink M AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Eze, Chetachukwu AU - Eze C AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Mills, Amanda AU - Mills A AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Stolz, Donna B AU - Stolz DB AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Jurczak, Michael AU - Jurczak M AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. FAU - Ramakrishnan, Sadeesh K AU - Ramakrishnan SK AD - Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15262., United States of America. Electronic address: ramaks@pitt.edu. LA - eng GR - K99 DK110537/DK/NIDDK NIH HHS/United States GR - R00 DK110537/DK/NIDDK NIH HHS/United States GR - P30 DK120531/DK/NIDDK NIH HHS/United States GR - S10 RR019003/RR/NCRR NIH HHS/United States GR - R01 DK119627/DK/NIDDK NIH HHS/United States GR - R01 DK114012/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200407 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Adrenergic beta-3 Receptor Agonists) RN - 0 (Insulin) SB - IM MH - Adipocytes, Beige/*physiology MH - Adipocytes, White/physiology MH - Adipose Tissue/cytology MH - Adrenergic beta-3 Receptor Agonists/pharmacology MH - Animals MH - Body Composition MH - *Caloric Restriction MH - Cell Fusion MH - Diet MH - Insulin/blood MH - Mice MH - Mice, Inbred C57BL MH - Mitophagy MH - *Organelle Biogenesis MH - Oxygen Consumption MH - Primary Cell Culture PMC - PMC7284285 MID - NIHMS1582607 OTO - NOTNLM OT - Beige adipocytes OT - Caloric restriction OT - Fission OT - Fusion OT - Mitochondrial biogenesis OT - Mitochondrial dynamics OT - Mitophagy COIS- Declaration of competing interest The authors declare no conflict of interests. EDAT- 2020/04/11 06:00 MHDA- 2020/08/04 06:00 PMCR- 2021/06/01 CRDT- 2020/04/11 06:00 PHST- 2020/01/29 00:00 [received] PHST- 2020/03/27 00:00 [revised] PHST- 2020/04/05 00:00 [accepted] PHST- 2020/04/11 06:00 [pubmed] PHST- 2020/08/04 06:00 [medline] PHST- 2020/04/11 06:00 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - S0026-0495(20)30089-5 [pii] AID - 10.1016/j.metabol.2020.154225 [doi] PST - ppublish SO - Metabolism. 2020 Jun;107:154225. doi: 10.1016/j.metabol.2020.154225. Epub 2020 Apr 7.