Role of microRNA-122 in hepatic lipid metabolism of the weanling female rat offspring exposed to prenatal and postnatal caloric restriction.
Animals
Body Weight
Caloric Restriction
/ adverse effects
Circadian Rhythm
Energy Metabolism
Fatty Acids
/ genetics
Female
Fetal Growth Retardation
/ etiology
Gene Expression
Growth Disorders
/ etiology
Hypothalamus
/ chemistry
Lipid Metabolism
/ genetics
Liver
/ chemistry
MicroRNAs
/ genetics
Organ Size
Pregnancy
RNA, Messenger
/ analysis
Rats
Rats, Sprague-Dawley
Weaning
Circadian rhythm
Energy balance
Fatty acid oxidation
Hepatic fatty acid synthesis
Hypothalamic genes
Intra-uterine growth restriction
microRNA-122
Journal
The Journal of nutritional biochemistry
ISSN: 1873-4847
Titre abrégé: J Nutr Biochem
Pays: United States
ID NLM: 9010081
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
21
12
2018
revised:
23
06
2019
accepted:
30
07
2019
pubmed:
21
10
2019
medline:
21
10
2020
entrez:
21
10
2019
Statut:
ppublish
Résumé
We examined the role of hepatocyte micro-RNA-122 and hypothalamic neuropeptides, in weanling (21d) female rats exposed to calorie restriction induced growth restriction either prenatally (IUGR), postnatally (PNGR) or both (IPGR) vs. ad lib fed controls (CON). IUGR were hyperinsulinemic, hyperleptinemic and dyslipidemic with high circulating miR-122. In contrast, PNGR and IPGR displayed insufficient glucose, insulin and leptin amidst high ketones with a dichotomy in circulating miR-122 of PNGR<IPGR = CON. Examination of livers revealed a reduction in miR-122 expression in PNGR and IPGR reflecting the hepatic size. This reduction of hepatic miR-122 was associated with an increase in specific target transcripts (ALDO-A, BCKDK, PPAR-β) and those mediating fatty acid oxidation (PGC-1α, CPT-1α), with a concomitant suppression of fatty acid and cholesterol synthesizing transcripts (FAS, HMGCR). Functionally, these changes correlated with increased fatty acid oxidation and mitochondrial CPT1α enzyme activity ex vivo. In vitro physiologic (serum starvation) and genetic manipulation of miR-122 in H4IIE hepatoma cells revealed fidelity in regulating ALDO-A/BCKDK, but an infidelity in perturbing fatty acid/cholesterol synthesizing and oxidizing gene transcripts. Nevertheless, changes in endogenous miR-122 maintained singular directionality while altering FAS/HMGCR and CPT-1α/PGC-1α, almost reflecting each other, and thereby maintaining a balance in fatty acid/cholesterol supply necessary to meet the in vitro demands of these rapidly proliferating transformed cells. Successive microarray based analysis, comparing IPGR to CON demonstrated differential expression of hypothalamic genes mediating cell proliferation and survival, appetite/energy balance, circadian rhythm and obesity/diabetes. We conclude that miR-122 regulates genes mediating fatty acid/cholesterol metabolism in postnatal female rats, fueling the energy demand.
Identifiants
pubmed: 31630081
pii: S0955-2863(18)31235-X
doi: 10.1016/j.jnutbio.2019.108220
pmc: PMC6896790
mid: NIHMS1537551
pii:
doi:
Substances chimiques
Fatty Acids
0
MIRN122 microRNA, rat
0
MicroRNAs
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108220Subventions
Organisme : NICHD NIH HHS
ID : R01 HD041230
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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