Dietary fat and gut microbiota interactions determine diet-induced obesity in mice

Autor: Raphaela, Kübeck, Catalina, Bonet-Ripoll, Christina, Hoffmann, Alesia, Walker, Veronika Maria, Müller, Valentina Luise, Schüppel, Ilias, Lagkouvardos, Birgit, Scholz, Karl-Heinz, Engel, Hannelore, Daniel, Philippe, Schmitt-Kopplin, Dirk, Haller, Thomas, Clavel, Martin, Klingenspor
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
Diet-induced obesity resistance
Hsp90
heat shock protein 90
CIDEA
cell death inducing DFFA-like effector
COX4
cytochrome c oxidase subunit 4
BMR
basal metabolic rate
Cyp27a1
cholesterol 27 alpha-hydroxylase
Cholesterol
Dietary
Hprt1
hypoxanthine guanine phosphoribosyl transferase
Mice
DEE
daily energy expenditure
GF
germfree
MCA
muricholic acid
qPCR
quantitative real-time polymerase chain reaction
ANOVA
analysis of variance
Eef2
eukaryotic elongation factor 2
CA
cholic acid
PHFD
high-fat diet based on palm oil
Dhcr7
7-dehydrocholesterol reductase
Hmgcr
3-hydroxy-3-methylglutaryl Coenzyme A reductase
Cyp7a1
cholesterol 7 alpha-hydroxylase
Abcg8
ATP-binding cassette sub-family G member 8
HP
heat production
Tf2b
transcription factor II B
Cholesterol
High-fat diet
Adipose Tissue
Liver
Abcg5
ATP-binding cassette sub-family G member 5
Original Article
CD
control diet
Akr1d1
aldo-keto-reductase family member 1
PRDM16
PR domain containing 16
LHFD
high-fat diet based on lard
lcsh:Internal medicine
Hsd11b1
hydroxysteroid (11-β) dehydrogenase 1
TCA
taurocholic acid
Srebf1
sterol regulatory element binding transcription factor 1
Energy balance
Ldlr
low density lipoprotein receptor
Diet
High-Fat
digestive system
SPF
specific pathogen free
GUSB
beta-glucuronidase
UDCA
ursodeoxycholic acid
CDCA
chenodeoxycholic acid
Nr1h2
nuclear receptor subfamily 1
group H
member 2 (liver X receptor β)
UCP1
uncoupling protein 1
Animals
UPLC-TOF-MS
ultraperformance liquid chromatography-time of flight-mass spectrometry
Obesity
Germfree
FT-IR
Fourier transform-infrared spectroscopy
lcsh:RC31-1245
Nr1h3
nuclear receptor subfamily 1
group H
member 3 (liver X receptor α)
TMCA
Tauromuricholic acid
Diet-induced Obesity Resistance
Energy Balance
High-fat Diet
DIO
diet-induced obesity
Lipid Metabolism
Dietary Fats
Gastrointestinal Microbiome
Mice
Inbred C57BL
Hmgcs
3-hydroxy-3-methylglutaryl Coenzyme A synthase 1
DCA
deoxycholic acid
Actb
beta actin
FT-ICR-MS
Fourier transform-Ion Cyclotron Resonance-Mass Spectrometry
HDCA
hyodeoxycholic acid
Nr1h4
nuclear receptor subfamily 1
group H
member 4 (farnesoid X receptor α)
Zdroj: Molecular Metabolism, Vol 5, Iss 12, Pp 1162-1174 (2016)
Mol. Metab. 5, 1162-1174 (2016)
Molecular Metabolism
ISSN: 2212-8778
Popis: Objective Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. Methods GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. Results GF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes) as a characteristic feature of normal SPF mice fed lard. Conclusions In conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.
Highlights • Cholesterol-based but not plant sterol-based high-fat diet protects germfree (GF) mice from diet-induced obesity (DIO). • DIO resistant GF mice show preferential carbohydrate oxidation, higher energy expenditure and energy and fat excretion. • DIO resistance in GF mice is accompanied by increased steroid hormone levels but decreased bile acid levels in the cecum. • Substrate oxidation and fat excretion in DIO resistant GF mice is linked to decreased hepatic Cyp7a1 and Nr1h4 expression.
Databáze: OpenAIRE
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