27-Hydroxycholesterol Promotes Adiposity and Mimics Adipogenic Diet-Induced Inflammatory Signaling.
Adipogenesis
/ drug effects
Adiposity
/ drug effects
Animals
Cytochrome P450 Family 7
/ genetics
Diet, High-Fat
/ adverse effects
Dietary Fats
/ adverse effects
Female
Gene Expression Regulation
/ drug effects
Hydroxycholesterols
Inflammation
/ chemically induced
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ chemically induced
Signal Transduction
/ drug effects
Steroid Hydroxylases
/ genetics
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
06
05
2019
accepted:
30
07
2019
pubmed:
7
8
2019
medline:
4
12
2019
entrez:
7
8
2019
Statut:
ppublish
Résumé
27-Hydroxycholesterol (27HC) is an abundant cholesterol metabolite and has detrimental effects on the cardiovascular system, whereas its impact on adiposity is not well known. In this study, we found that elevations in 27HC cause increased body weight gain in mice fed a high-fat/high-cholesterol diet in an estrogen receptor α-dependent manner. Regardless of diet type, body fat mass was increased by 27HC without changes in food intake or fat absorption. 27HC did not alter energy expenditure in mice fed a normal chow diet and increased visceral white adipose mass by inducing hyperplasia but not hypertrophy. Although 27HC did not augment adipocyte terminal differentiation, it increased the adipose cell population that differentiates to mature adipocytes. RNA sequencing analysis revealed that 27HC treatment of mice fed a normal chow diet induces inflammatory gene sets similar to those seen after high-fat/high-cholesterol diet feeding, whereas there was no overlap in inflammatory gene expression among any other 27HC administration/diet change combination. Histological analysis showed that 27HC treatment increased the number of total and M1-type macrophages in white adipose tissues. Thus, 27HC promotes adiposity by directly affecting white adipose tissues and by increasing adipose inflammatory responses. Lowering serum 27HC levels may lead to an approach targeting cholesterol to prevent diet-induced obesity.
Identifiants
pubmed: 31386147
pii: 5543973
doi: 10.1210/en.2019-00349
pmc: PMC6760292
doi:
Substances chimiques
Dietary Fats
0
Hydroxycholesterols
0
27-hydroxycholesterol
6T2NA6P5SQ
Steroid Hydroxylases
EC 1.14.-
Cytochrome P450 Family 7
EC 1.14.14.23
Cyp7b1 protein, mouse
EC 1.14.14.29
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2485-2494Subventions
Organisme : NHLBI NIH HHS
ID : R56 HL127037
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA ES070065
Pays : United States
Informations de copyright
Copyright © 2019 Endocrine Society.
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