Mouse Abdominal Fat Depots Reduced by Butyric Acid-Producing Leuconostoc mesenteroides

Abstract

The activation of peroxisome proliferator-activated rece ptor gamma (PPAR-γ) is known to induce the differentiation of adipocytes. This study aimed to investigate the probiotic effect of Leuconostoc mesenteroides (L. mesenteroides) on high-fat diet (HFD)-induced PPAR-γ activation and abdominal fat depots. Incubation of differentiated 3T3-L1 adipocytes with media of L. mesenteroides EH-1, a butyric acid-producing strain, significantly reduced the amounts of lipid droplets. The oral administration of L. mesenteroides EH-1 produced large amounts (>1 mM) of butyric acid in cecum and attenuated the HFD-induced upregulation of PPAR-γ and accumulation of abdominal fats in mice. The combination of 2% glucose with L. mesenteroides EH-1 increased the production of butyric acid and potentiated the probiotic activity of L. mesenteroides EH-1 against the formation of lipid droplets in 3T3-L1 adipocytes as well as abdominal fats in HFD-fed mice. The inhibition of free fatty acid receptor 2 (Ffar2) by its antagonist, GLPG-0974, markedly diminished the probiotic effects of L. mesenteroides EH-1 plus glucose on the suppression of HFD-induced PPAR-γ and abdominal fats. Besides demonstrating the probiotic value of L. mesenteroides EH-1, our results highlight the possible therapy targeting the butyric acid-activated Ffar2 pathway to reduce abdominal fats.

Fecal microbiota transplantation revealed the function of folic acid on reducing abdominal fat deposition in broiler chickens mediated by gut microbiota

“…Notably, Oscillospira exhibited lower abundance in gut of obesity and the early study involving monozygotic twins revealed a strong inverse correlation between Oscillospira and obesity ( Tims et al, 2013 ). A substantial of evidence suggested that Oscillospira played a significant role in metabolic activities related to obesity ( Gophna et al, 2017 ), while Oscillospira was capable of producing various short-chain fatty acids ( SCFAs ) dominated by butyric acid ( Gophna et al, 2017 ; Jiao et al, 2018 ) and was significantly associated with adipose and inflammatory diseases ( Konikoff and Gophna, 2016 ; Gophna et al, 2017 ; Yang et al, 2020 ). In addition, it is crucial that gut bacteria could produce large amounts of folic acid and other B vitamins for body utilize ( Morowitz et al, 2011 ).…”

Short Chain Fatty Acids Protect the Cognitive Function of Sepsis Associated Encephalopathy Mice via GPR43

“…Several mice died during the experiment and the final sample size of each group was as follows: sham group (n = 10), CLP group (n = 10), CLP+SCFAs group (n = 12), and CLP+SCFAs+GLPG0974 group (n = 10). In the CLP+SCFAs+GLPG0974 group, SCFAs (acetate: propionate: butyrate at a ratio of 3: 1: 1) at 500 mg/kg body weight were administrated intra-gastrically two times a day for 7 consecutive days before CLP surgery, and GLPG0974 at 1 mg/kg body weight were given every 3 days for 24 days by oral gavage right before administration of SCFAs (15,20). Saline was administrated as vehicle.…”

Chemogenetic Approaches to Explore the Functions of Free Fatty Acid Receptor 2

“…Although BTI-A-404 has not been used in subsequent studies, GLPG0974 has been employed to help define roles of FFA2 in human cells and tissues [24][25][26]. Surprisingly, however, given its lack of affinity for rat and mouse FFA2, GLPG0974 has also been reported to be effective in blocking a potentially FFA2-mediated effect in rat small intestine [27] and in both a mouse model of type II diabetes [28] and the probiotic effects of Leuconostoc mesenteroide in mice [29]. Such effects of GLPG0974 in rodent models are incompatible with the known lack of affinity of this ligand at mouse and rat FFA2 and must, therefore reflect unknown 'off-target' actions of GLPG0974.…”