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

2019-12-27
Scientific reports 9(1)

PubMed: 31882939
DOI: 10.1038/s41598-019-56817-w

Study Design

Population: mice fed a high-fat diet (HFD)
Methods: administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD); lactate was also tested in 3T3-L1 adipocytes

Rigorous Journal

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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus amylovorus	—	Increased Adipose Browning	Beneficial	Large	View source LKU4 administration enhanced mitochondrial levels and function, as well as the thermogenic gene program... in subcutaneous inguinal WAT... thereby promoting browning of white adipocytes.
Lactobacillus amylovorus	—	Increased Body Temperature	Beneficial	Small	View source LKU4 administration... also increased body temperature.
Lactobacillus amylovorus	—	Reduced Obesity	Beneficial	Moderate	View source Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function... increased body temperature... leading to inhibition of diet-induced obesity.