Bifidobacterium animalis subsp. lactis A6 Alleviates Obesity Associated with Promoting Mitochondrial Biogenesis and Function of Adipose Tissue in Mice

Abstract

Probiotics are widely known for their health benefits. Mitochondrial dysfunction is related to obesity. The aim of this study was to illuminate whether Bifidobacterium animalis subsp. lactis A6 (BAA6) could improve obesity due to increased mitochondrial biogenesis and function of adipose tissues. Four-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 17 weeks. For the final eight weeks, the HFD group was divided into three groups including HFD, HFD with BAA6 (HFD + BAA6 group), and HFD with Akkermansia muciniphila (AKK) (HFD + AKK group as positive control). The composition of the microbiota, serum lipopolysaccharides (LPS), and mitochondrial biosynthesis and function of epididymal adipose tissues were measured. Compared with the HFD group, body weight, relative fat weight, the relative abundance of Oscillibacter and Bilophila, and serum LPS were significantly decreased in the HFD + BAA6 and HFD + AKK groups (p < 0.05). Furthermore, the addition of BAA6 and AKK increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (by 21.53- and 18.51-fold), estrogen-related receptor α (ERRα) (by 2.83- and 1.24-fold), and uncoupling protein-1 (UCP-1) (by 1.51- and 0.60-fold) in epididymal adipose tissues. Our results suggest that BAA6 could improve obesity associated with promoting mitochondrial biogenesis and function of adipose tissues in mice.

Keywords: Bifidobacterium animalis subsp. lactis A6; lipopolysaccharides; mitochondrial biogenesis and functions; obesity; tumor necrosis factor α.

Figure 1

Effects of oral administration of Bifidobacterium animalis subsp. lactis A6 (BAA6) or Akkermansia muciniphila (AKK) on metabolic parameters in high-fat diet (HFD)-fed mice. (A) Body weight, (B) body weight gain, (C) relative adipose tissue, and serum levels of (D) total triglyceride (TG), (E) total cholesterol (TC), and (F) low-density lipoprotein cholesterol (LDL-C) following daily treatment with 10⁹ colony-forming units (CFU)/kg of BAA6 or AKK. Values are expressed as means ± SD (n = 6). Bars with different lowercase letters denote significant differences among groups (p < 0.05). HFD, fed high-fat diet for 17 weeks; HFD + BAA6, fed high-fat diet and treated with Bifidobacterium animalis subsp. lactis A6 for the final eight weeks; HFD + AKK, fed high-fat diet and treated with Akkermansia muciniphila for the final eight weeks; ND, fed normal diet for 17 weeks.

Figure 2

Effects of BAA6 or AKK on lipid metabolism for epididymal adipose tissues in HFD-fed mice. Messenger RNA (mRNA) expression levels of (A) fatty acid synthase (Fas) and (B) hormone-sensitive lipase (Hsl), and protein expression levels of (C) FAS and (D) HSL following daily treatment with 10⁹ CFU/kg BAA6 or AKK. Values are expressed as means ± SD (n = 6). Bars with different lowercase letters denote significant differences among groups (p < 0.05).

Figure 3

Effects of BAA6 or AKK on gut microbiota in HFD-fed mice. (A) Relative abundance of the gut microbial community at the genus level. (B) Principal component analysis (PCA) score plots at the genus level. (C) Histogram of the linear discriminant analysis (LDA) scores between the ND and HFD groups, and (D) histogram of LDA scores among the HFD, HFD + AKK, and HFD + BAA6 groups. The differences with an LDA score greater than three are considered significant. n = 6 mice/group. HFD0, fed high-fat diet for nine weeks; ND0, fed normal diet for nine weeks.

Figure 4

Effects of oral administration of BAA6 or AKK on inflammation in HFD-fed mice. (A) The level of serum lipopolysaccharides (LPS). (B) Tumor necrosis factor α (TNF-α) concentration in epididymal adipose tissues. Protein expression levels of (C) phosphorylated c-Jun N-terminal kinase (p-JNK)/JNK and (D) phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)/ERK1/2 in epididymal fat tissues following daily treatment with 10⁹ CFU/kg BAA6 or AKK. Values are expressed as means ± SD (n = 6). Bars with different lowercase letters denote significant differences among groups (p < 0.05).

Figure 5

Effects of oral administration of BAA6 or AKK on endothelial nitric oxide synthase (eNOS) expression and mitochondrial biogenesis of epididymal adipose tissues in HFD-fed mice. (A) mRNA expression levels of endothelial nitric oxide synthase (eNos), (B) peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α), and (C) nuclear respiratory factor-1 (Nrf-1) and protein expression levels of (D) eNOS, (E) PGC-1α, and (F) NRF-1 following daily treatment with 10⁹ CFU/kg BAA6 or AKK. Values are expressed as means ± SD (n = 6). Bars with different lowercase letters denote significant differences among groups (p < 0.05).

Figure 6

Effects of oral administration of BAA6 or AKK on mitochondrial function of epididymal fat tissues in HFD-fed mice. mRNA expression levels of (A) estrogen-related receptor α (Errα) and (B) uncoupling protein-1 (Ucp-1), protein expression levels of (C) ERRα and (D) UCP-1, and enzyme activities of (E) β-hydroxyacyl CoA dehydrogenase (β-HAD) and (F) carnitine palmitoyl transferase I (CPT-I) following daily treatment with 10⁹ CFU/kg of BAA6 or AKK. Values are expressed as means ± SD (n = 6). Bars with different lowercase letters denote significant differences among groups (p < 0.05).