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

Abstract

ObjectiveGut 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.MethodsGF 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.ResultsGF 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.ConclusionsIn conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

“…This genus was shown to be isolated from the intestine of obese mice and produces the short-chain fatty acids, acetate and butyrate [54]. The abundance of Acetatifactor in the gut has also been shown to be related to lard intake in mice and correlated with the concentrations of secondary bile acids in mouse cecum [55]. We also have observed increases in Acetatifactor genus with 0.25% (w/w) milk SM feeding on a low-fat diet background (Norris and Blesso, unpublished observations 2016).…”

The Changes of Fecal Steroid Hormones and Bacterial Composition in Different Gestation Stages of Meishan Sows

“…In later pregnancy, the mother develops a physiological insulin resistance that to store an adequate nutrient supply for fetus growth and lactation energy demand, therefore, excessive adiposity is usual for later pregnancy [18]. In addition, the high level of E 2 and CORT in later period of pregnancy also indicate the metabolic changes, E 2 has the activity to stimulate energy expenditure, CORT can stimulate food intake, reduce food passage rate [19]. Thus, high composition of Burkholderiales and Selenomonadales order in stool microbiota may relate to the metabolic variation in later pregnancy of Meishan sows.…”

Gut Microbiota-Dependent Modulation of Energy Metabolism

“…Thus, even when the fermentation rate is low, the presence of a gut microbiota leads to a positive energy balance. However, the microbiota-diet interaction is complex, and the resistance to DIO in mice lacking a microbiota depends on the composition and fat source of the high-fat diet (HFD) [17]. Increased energy expenditure, as well as increased fecal fat content and energy excretion, contribute to the DIO resistance in GF mice when fed a lard-based HFD.…”