PMID- 37994388
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240216
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 23
IP  - 2
DP  - 2024 Feb
TI  - Cpt1a silencing in AgRP neurons improves cognitive and physical capacity and 
      promotes healthy aging in male mice.
PG  - e14047
LID - 10.1111/acel.14047 [doi]
LID - e14047
AB  - Orexigenic neurons expressing agouti-related protein (AgRP) and neuropeptide Y in 
      the arcuate nucleus (ARC) of the hypothalamus are activated in response to 
      dynamic variations in the metabolic state, including exercise. We previously 
      observed that carnitine palmitoyltransferase 1a (CPT1A), a rate-limiting enzyme 
      of mitochondrial fatty acid oxidation, is a key factor in AgRP neurons, 
      modulating whole-body energy balance and fluid homeostasis. However, the effect 
      of CPT1A in AgRP neurons in aged mice and during exercise has not been explored 
      yet. We have evaluated the physical and cognitive capacity of adult and aged 
      mutant male mice lacking Cpt1a in AgRP neurons (Cpt1a KO). Adult Cpt1a KO male 
      mice exhibited enhanced endurance performance, motor coordination, locomotion, 
      and exploration compared with control mice. No changes were observed in 
      anxiety-related behavior, cognition, and muscle strength. Adult Cpt1a KO mice 
      showed a reduction in gastrocnemius and tibialis anterior muscle mass. The 
      cross-sectional area (CSA) of these muscles were smaller than those of control 
      mice displaying a myofiber remodeling from type II to type I fibers. In aged 
      mice, changes in myofiber remodeling were maintained in Cpt1a KO mice, avoiding 
      loss of physical capacity during aging progression. Additionally, aged Cpt1a KO 
      mice revealed better cognitive skills, reduced inflammation, and oxidative stress 
      in the hypothalamus and hippocampus. In conclusion, CPT1A in AgRP neurons appears 
      to modulate health and protects against aging. Future studies are required to 
      clarify whether CPT1A is a potential antiaging candidate for treating diseases 
      affecting memory and physical activity.
CI  - (c) 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & 
      Sons Ltd.
FAU - Ibeas, Kevin
AU  - Ibeas K
AUID- ORCID: 0000-0002-9981-5669
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la 
      Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
FAU - Grinan-Ferre, Christian
AU  - Grinan-Ferre C
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of 
      Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion en Red, Enfermedades Neurodegenerativas (CIBERNED, 
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Del Mar Romero, Maria
AU  - Del Mar Romero M
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la 
      Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
FAU - Sebastian, David
AU  - Sebastian D
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas 
      Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
FAU - Bastias-Perez, Marianela
AU  - Bastias-Perez M
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Gomez, Roberto
AU  - Gomez R
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Soler-Vazquez, M Carmen
AU  - Soler-Vazquez MC
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Zagmutt, Sebastian
AU  - Zagmutt S
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Pallas, Merce
AU  - Pallas M
AUID- ORCID: 0000-0003-3095-4254
AD  - Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of 
      Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion en Red, Enfermedades Neurodegenerativas (CIBERNED, 
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Castell, Margarida
AU  - Castell M
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la 
      Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
AD  - Institut de Recerca en Nutricio i Seguretat Alimentaria (INSA-UB), Universitat de 
      Barcelona, Santa Coloma de Gramenet, Spain.
FAU - Belsham, Denise D
AU  - Belsham DD
AD  - Department of Physiology, Obstetrics and Gynaecology and Medicine, University of 
      Toronto, Toronto, Ontario, Canada.
FAU - Mera, Paula
AU  - Mera P
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Herrero, Laura
AU  - Herrero L
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la 
      Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
FAU - Serra, Dolors
AU  - Serra D
AUID- ORCID: 0000-0002-4936-4206
AD  - Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, 
      Universitat de Barcelona, Barcelona, Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de 
      Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la 
      Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
LA  - eng
GR  - Grant CB06/03/0001/Biomedical Research Centre in Pathophysiology of Obesity and 
      Nutrition (CIBEROBN)/
GR  - PID2020-114953RB-C21/Ministerio de Ciencia e Innovacion/
PT  - Journal Article
DEP - 20231122
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Agouti-Related Protein)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.3.1.21 (CPT1B protein, mouse)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - Agouti-Related Protein/genetics/metabolism
MH  - Arcuate Nucleus of Hypothalamus/metabolism
MH  - *Carnitine O-Palmitoyltransferase/genetics/metabolism
MH  - *Healthy Aging
MH  - Hypothalamus/metabolism
MH  - Neurons/metabolism
PMC - PMC10861206
OTO - NOTNLM
OT  - AgRP neurons
OT  - CPT1A
OT  - aging
OT  - cognitive behavior
OT  - physical activity
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2023/11/23 06:42
MHDA- 2024/02/13 00:42
PMCR- 2023/11/22
CRDT- 2023/11/23 04:13
PHST- 2023/11/08 00:00 [revised]
PHST- 2023/06/05 00:00 [received]
PHST- 2023/11/10 00:00 [accepted]
PHST- 2024/02/13 00:42 [medline]
PHST- 2023/11/23 06:42 [pubmed]
PHST- 2023/11/23 04:13 [entrez]
PHST- 2023/11/22 00:00 [pmc-release]
AID - ACEL14047 [pii]
AID - 10.1111/acel.14047 [doi]
PST - ppublish
SO  - Aging Cell. 2024 Feb;23(2):e14047. doi: 10.1111/acel.14047. Epub 2023 Nov 22.