Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice.
Nat Commun
; 14(1): 1685, 2023 03 27.
Article
em En
| MEDLINE
| ID: mdl-36973248
ABSTRACT
The circadian clock is an endogenous time-tracking system that anticipates daily environmental changes. Misalignment of the clock can cause obesity, which is accompanied by reduced levels of the clock-controlled, rhythmic metabolite NAD+. Increasing NAD+ is becoming a therapy for metabolic dysfunction; however, the impact of daily NAD+ fluctuations remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+ treatment for diet-induced metabolic disease in mice. Increasing NAD+ prior to the active phase in obese male mice ameliorated metabolic markers including body weight, glucose and insulin tolerance, hepatic inflammation and nutrient sensing pathways. However, raising NAD+ immediately before the rest phase selectively compromised these responses. Remarkably, timed NAD+ adjusted circadian oscillations of the liver clock until completely inverting its oscillatory phase when increased just before the rest period, resulting in misaligned molecular and behavioral rhythms in male and female mice. Our findings unveil the time-of-day dependence of NAD+-based therapies and support a chronobiology-based approach.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Relógios Circadianos
/
Doenças Metabólicas
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2023
Tipo de documento:
Article