PMID- 30920127 OWN - NLM STAT- MEDLINE DCOM- 20200914 LR - 20210109 IS - 1474-9726 (Electronic) IS - 1474-9718 (Print) IS - 1474-9718 (Linking) VI - 18 IP - 3 DP - 2019 Jun TI - Long-term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity. PG - e12948 LID - 10.1111/acel.12948 [doi] LID - e12948 AB - Age-related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR. To elucidate the role of CR in delaying early signs of aging, young (3 months), middle-aged (12 months), and old (20 months) mice fed al libitum and middle-aged and old mice subjected to early-onset CR were used. We show that impaired plasticity of subcutaneous WAT (scWAT) contributes to IR, which is already evident in middle-aged mice. Moreover, alteration of thyroid axis status with age is an important factor contributing to BAT dysfunction in middle-aged animals. Both defects in WAT and BAT/beige cells are ameliorated by CR. Accordingly, CR attenuated the age-related decline in scWAT function and decreased the extent of fibro-inflammation. Furthermore, CR promoted scWAT browning. In brief, our study identifies the contribution of scWAT impairment to age-associated metabolic dysfunction and identifies browning in response to food restriction, as a potential therapeutic strategy to prevent the adverse metabolic effects in middle-aged animals. CI - (c) 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. FAU - Corrales, Patricia AU - Corrales P AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Vivas, Yurena AU - Vivas Y AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Izquierdo-Lahuerta, Adriana AU - Izquierdo-Lahuerta A AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Horrillo, Daniel AU - Horrillo D AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Seoane-Collazo, Patricia AU - Seoane-Collazo P AD - NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain. FAU - Velasco, Ismael AU - Velasco I AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Torres, Lucia AU - Torres L AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Lopez, Yamila AU - Lopez Y AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Martinez, Carmen AU - Martinez C AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. FAU - Lopez, Miguel AU - Lopez M AD - NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. FAU - Ros, Manuel AU - Ros M AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. AD - MEMORISM Research Unit, Institute of Biomedical Research "Alberto Sols" (CSIC), University Rey Juan Carlos, Madrid, Spain. FAU - Obregon, Maria Jesus AU - Obregon MJ AD - MEMORISM Research Unit, Institute of Biomedical Research "Alberto Sols" (CSIC), University Rey Juan Carlos, Madrid, Spain. AD - Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomedicas (IIB), Centro Mixto CSIC-UAM (Consejo Superior Investigaciones Cientificas and Universidad Autonoma de Madrid), Madrid, Spain. FAU - Medina-Gomez, Gema AU - Medina-Gomez G AUID- ORCID: 0000-0001-8169-681X AD - Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain. AD - MEMORISM Research Unit, Institute of Biomedical Research "Alberto Sols" (CSIC), University Rey Juan Carlos, Madrid, Spain. LA - eng GR - S2010/BMD-2433/Community of Madrid/International GR - B2017BMD-3684/Community of Madrid/International GR - 2015-CP079/Xunta de Galicia/International GR - FPU12/01827/Ministerio de Educacion, Cultura y Deporte/International GR - BFU2013-47384-R/Spanish Ministry of Economy and Competitiveness/International GR - BFU2016-78951-R/Spanish Ministry of Economy and Competitiveness/International GR - SAF2012-32491/Spanish Ministry of Economy and Competitiveness/International GR - SAF2015-71026-R/Spanish Ministry of Economy and Competitiveness/International GR - BFU2015-70454-REDT/Spanish Ministry of Economy and Competitiveness/International GR - BFU2017-90578-REDT/Spanish Ministry of Economy and Competitiveness/International GR - 281854/European Community's Seventh Framework Programme (FP7/2007-2013)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190328 PL - England TA - Aging Cell JT - Aging cell JID - 101130839 SB - IM MH - Adipose Tissue, Brown/*metabolism MH - Adipose Tissue, White/*metabolism MH - Aging/*metabolism MH - Animals MH - *Caloric Restriction MH - Glucose Tolerance Test MH - Male MH - Mice MH - Mice, 129 Strain MH - Positron Emission Tomography Computed Tomography PMC - PMC6516146 OTO - NOTNLM OT - adipose tissue OT - aging OT - caloric restriction OT - fibro-inflammation OT - insulin resistance OT - thyroid hormone COIS- None declared. EDAT- 2019/03/29 06:00 MHDA- 2020/09/15 06:00 PMCR- 2019/06/01 CRDT- 2019/03/29 06:00 PHST- 2018/05/07 00:00 [received] PHST- 2019/02/04 00:00 [revised] PHST- 2019/03/01 00:00 [accepted] PHST- 2019/03/29 06:00 [pubmed] PHST- 2020/09/15 06:00 [medline] PHST- 2019/03/29 06:00 [entrez] PHST- 2019/06/01 00:00 [pmc-release] AID - ACEL12948 [pii] AID - 10.1111/acel.12948 [doi] PST - ppublish SO - Aging Cell. 2019 Jun;18(3):e12948. doi: 10.1111/acel.12948. Epub 2019 Mar 28.