Dietary fat and gut microbiota interactions determine diet-induced obesity in mice.
Study Goal
The researchers sought to identify dietary constituents that determine susceptibility to body fat accretion in germfree mice and explore the interaction between gut microbiota and cholesterol metabolism.
Results Summary
Germfree mice were resistant to diet-induced obesity when fed a cholesterol-rich lard-based high-fat diet but not a cholesterol-free palm oil-based diet. This resistance was linked to increased energy expenditure, carbohydrate oxidation, and fecal fat excretion, along with shifts in bile acid and steroid metabolites.
Population
Germfree and specific pathogen-free male C57BL/6N mice.
Effective Dosage
Not specified (high-fat diets based on lard or palm oil).
Duration
4 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
cholesterol-rich lard-based high-fat diet | decrease | diet-induced obesity (DIO) | GF mice | completely resistant | completely DIO resistant | #1 |
cholesterol-free palm oil-based high-fat diet | no change | diet-induced obesity (DIO) | GF mice | - | DIO was independent of gut microbiota | #2 |
cholesterol-rich lard-based high-fat diet | increase | energy expenditure | GF lard-fed mice | - | increased | #3 |
cholesterol-rich lard-based high-fat diet | increase | carbohydrate oxidation | GF lard-fed mice | - | preferential carbohydrate oxidation | #4 |
cholesterol-rich lard-based high-fat diet | increase | fecal fat and energy excretion | GF lard-fed mice | - | increased | #5 |
cholesterol-rich lard-based high-fat diet | increase | 17β-estradiol | GF lard-fed mice | significant rise | significant rise | #6 |
cholesterol-rich lard-based high-fat diet | decrease | cecal bile acid levels | GF lard-fed mice | - | decreased | #7 |
cholesterol-rich lard-based high-fat diet | decrease | hepatic expression of genes involved in bile acid synthesis | GF lard-fed mice | - | decreased | #8 |
palm-oil based high-fat diet | decrease | metabolic adaptations | GF mice | largely attenuated | largely attenuated | #9 |
cholesterol-rich lard | increase | bile acid levels and specific bacteria of the order Clostridiales | normal SPF mice | positive correlation | positive correlation | #10 |
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.