Effects of imidazoline-like drugs on liver and adipose tissues, and their role in preventing obesity and associated cardio-metabolic disorders.
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
09
07
2018
accepted:
10
03
2019
revised:
31
01
2019
pubmed:
31
3
2019
medline:
2
6
2020
entrez:
31
3
2019
Statut:
ppublish
Résumé
We previously observed that selective agonists of the sympatho-inhibitory I Young Zucker fa/fa rats were treated with LNP599 (10 mg/kg/day) for 12 weeks. Effects on body weight, adiposity (regional re-distribution, morphology, and function of adipose tissues), cardiovascular and metabolic homeostasis, and liver function were evaluated. Direct effects on insulin and AMP-activated protein kinase (AMPK) signaling were studied in human hepatoma HepG2 cells. LNP599 treatment limited the age-dependent remodeling and inflammation of subcutaneous, epididymal, and visceral adipose tissues, and prevented total fat deposits and the development of obesity. Body-weight stabilization was not related to reduced food intake but rather to enhanced energy expenditure and thermogenesis. Cardiovascular and metabolic parameters were also improved and were significantly correlated with body weight but not with plasma norepinephrine. Insulin and AMPK signaling were enhanced in hepatic tissues of treated animals, whereas blood markers of hepatic disease and pro-inflammatory cytokine levels were reduced. In cultured HepG2 cells, LNP ligands phosphorylated AMPK and the downstream acetyl-CoA carboxylase and prevented oleic acid-induced intracellular lipid accumulation. They also significantly potentiated insulin-mediated AKT activation and this was independent from AMPK. Selective I
Sections du résumé
BACKGROUND/OBJECTIVES
We previously observed that selective agonists of the sympatho-inhibitory I
METHODS
Young Zucker fa/fa rats were treated with LNP599 (10 mg/kg/day) for 12 weeks. Effects on body weight, adiposity (regional re-distribution, morphology, and function of adipose tissues), cardiovascular and metabolic homeostasis, and liver function were evaluated. Direct effects on insulin and AMP-activated protein kinase (AMPK) signaling were studied in human hepatoma HepG2 cells.
RESULTS
LNP599 treatment limited the age-dependent remodeling and inflammation of subcutaneous, epididymal, and visceral adipose tissues, and prevented total fat deposits and the development of obesity. Body-weight stabilization was not related to reduced food intake but rather to enhanced energy expenditure and thermogenesis. Cardiovascular and metabolic parameters were also improved and were significantly correlated with body weight but not with plasma norepinephrine. Insulin and AMPK signaling were enhanced in hepatic tissues of treated animals, whereas blood markers of hepatic disease and pro-inflammatory cytokine levels were reduced. In cultured HepG2 cells, LNP ligands phosphorylated AMPK and the downstream acetyl-CoA carboxylase and prevented oleic acid-induced intracellular lipid accumulation. They also significantly potentiated insulin-mediated AKT activation and this was independent from AMPK.
CONCLUSIONS
Selective I
Identifiants
pubmed: 30926950
doi: 10.1038/s41366-019-0342-z
pii: 10.1038/s41366-019-0342-z
doi:
Substances chimiques
(3-chloro-2-methylphenyl)-(4-methyl-4,5-dihydro-3H-pyrrol-2-yl)amine
0
Aniline Compounds
0
Imidazolines
0
Pyrroles
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM