Lactobacillus acidophilus NS1 attenuates diet-induced obesity and fatty liver

Abstract

Obesity is a major threat to public health, and it is strongly associated with insulin resistance and fatty liver disease. Here, we demonstrated that administration of <i>Lactobacillus acidophilus</i> NS1 (LNS1) significantly reduced obesity and hepatic lipid accumulation, with a concomitant improvement in insulin sensitivity, in high-fat diet (HFD)-fed mice. Furthermore, administration of LNS1 inhibited the effect of HFD feeding on the SREBP-1c and PPARα signaling pathways and reduced lipogenesis with an increase in fatty acid oxidation in <i>ex vivo</i> livers from HFD-fed mice. These LNS1 effects were confirmed in HepG2 cells and <i>ex vivo</i> livers by treatment with LNS1 culture supernatant (LNS1-CS). Interestingly, AMPK phosphorylation and activity in the liver of HFD-fed mice were increased by administration of LNS1. Consistently, chemical inhibition of AMPK with compound C, a specific inhibitor of AMPK, dramatically reduced the effect of LNS1-CS on lipid metabolism in HepG2 cells and <i>ex vivo</i> livers by modulating the SREBP-1c and PPARα signaling pathways. Furthermore, administration of LNS1 to HFD-fed mice significantly improved insulin resistance and increased Akt phosphorylation in the liver, white adipose tissue and skeletal muscle. Together, these data suggest that LNS1 may prevent diet-induced obesity and related metabolic disorders by improving lipid metabolism and insulin sensitivity through an AMPK→SREBP-1c/PPARα signaling pathway.