Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice.
Adipose Tissue
/ drug effects
Adiposity
/ drug effects
Animals
Bacteria
/ classification
Body Weight
/ drug effects
Combined Modality Therapy
Diet, Fat-Restricted
Enzyme Inhibitors
/ administration & dosage
Gastrointestinal Microbiome
/ drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Nicotinamide N-Methyltransferase
/ antagonists & inhibitors
Obesity
/ diet therapy
Quinolinium Compounds
/ administration & dosage
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
12
08
2021
accepted:
01
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
3
3
2022
Statut:
epublish
Résumé
Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances. Collectively, these results provide a novel foundation for future investigations.
Identifiants
pubmed: 35013352
doi: 10.1038/s41598-021-03670-5
pii: 10.1038/s41598-021-03670-5
pmc: PMC8748953
doi:
Substances chimiques
Enzyme Inhibitors
0
Quinolinium Compounds
0
Nicotinamide N-Methyltransferase
EC 2.1.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
484Subventions
Organisme : NIAID NIH HHS
ID : P01 AI152999
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR013497
Pays : United States
Organisme : NIH HHS
ID : U01-AI24290
Pays : United States
Organisme : NIH HHS
ID : NIDDK 1R41DK119052-01
Pays : United States
Organisme : NIDDK NIH HHS
ID : R41 DK119052
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG024832
Pays : United States
Informations de copyright
© 2022. The Author(s).
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