Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling

Abstract

Browning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.

Beneficial Effects of Lactobacillus plantarum Strains on Non-Alcoholic Fatty Liver Disease in High Fat/High Fructose Diet-Fed Rats

“…This interest extends to the improvement of various inflammatory diseases. Particularly, probiotic treatment is an effective and safe approach to reversing metabolic abnormalities observed not only in obesity [28,29], but also in NAFLD [30]. In this study, treatment with two L. plantarum strains, K2 and K6, improved HF/HF diet-induced NAFLD in rats by regulating liver function, serum lipid levels, and lipogenesis via the AMPK pathway.…”

Non-Viable Lactobacillus johnsonii JNU3402 Protects against Diet-Induced Obesity

“…Recent studies in mice and human volunteers showed that several strains of probiotic bacteria, such as Lactobacillus acidophilus NS1, Lactobacillus amylovorus KU4, and Akkermansia muciniphila , ameliorate obesity and associated metabolic disorders [ 3 , 4 , 17 ]. To determine whether NV probiotic bacteria have a similar effect on the reduction of diet-induced obesity, 7-week-old male mice were fed HFD with or without oral administration of NV-LJ3402 for 14 weeks.…”

“…In addition, NV-LJ3402-CM was added to HEK293T cells for 24 h to test its effect on the activities of transcription factors. Adipocyte differentiation of 3T3-L1 cells and transfections were performed as previously described [ 4 ].…”

“…Total RNA was isolated from 3T3-L1 cells and WATs using Trizol reagent (Invitrogen, Waltham, MA, USA), and cDNA was synthesized from 1 μg total RNA using Moloney Murine Leukemia Virus (M-MLV)Reverse Transcriptase (Promega, Madison, WIS, USA). Real time-quantitative PCR (RT-qPCR) was performed as previously described [ 4 ], and the results were normalized to 36B4 mRNA expression. Relative quantification of PCR products was calculated by the difference in Ct values between the target and 36B4 genes using the 2 −ΔΔCt method.…”

“…Lactobacillus acidophilus NS1 inhibits obesity in high-fat diet (HFD)-fed mice by increasing hepatic fatty acid oxidation with decreased lipogenesis, improving HFD-induced insulin resistance, nonalcoholic fatty liver disease, and hyperlipidemia [ 3 ]. In addition, another Lactobacillus strain, Lactobacillus amylovorus KU4, promotes the browning of WAT in HFD-fed mice, leading to the suppression of HFD-induced adiposity with reduced lipid deposition in metabolic tissues, such as liver and WAT as well as improved insulin sensitivity [ 4 ]. The World Health Organization and the Food and Agriculture Organization of the United Nations define probiotics as living beneficial microorganisms [ 5 ].…”