Fragmented Lactic Acid Bacterial Cells Activate Peroxisome Proliferator-Activated Receptors and Ameliorate Dyslipidemia in Obese Mice

Abstract

Recent studies suggest that peroxisome proliferator-activated receptor (PPAR) activation ameliorates metabolic disorders, including dyslipidemia. To identify an effective PPAR agonist, we screened the in vitro PPARα/γ activation ability of organic solvent extracts from food-oriented bacterial strains belonging to 5 genera and 32 species, including lactic acid bacteria, and of these, Lactobacillus amylovorus CP1563 demonstrated the highest PPARα/γ agonist activity. We also found that physical fragmentation of the strain could substitute organic solvent extraction for the expression of CP1563 activity in vitro. For functional food manufacturing, we selected the fragmented CP1563 and conducted subsequent animal experiments. In an obese mouse model, we found that treatment with fragmented CP1563 for 12 weeks decreased the levels of low-density lipoprotein (LDL)-cholesterol and triglyceride in plasma, significantly decreased the atherosclerosis index, and increased the plasma high-density lipoprotein (HDL)-cholesterol level. Thus, we conclude that fragmented CP1563 may be a candidate for the prevention and treatment of dyslipidemia.

Dual function of Lactobacillus kefiri DH5 in preventing high‐fat‐diet‐induced obesity: direct reduction of cholesterol and upregulation of PPAR‐α in adipose tissue

“…In addition, the HFD-DH5 group showed a lower body weight gain, adipose tissue weight, hepatic steatosis, and diameter of adipocytes than the other groups, and this result is consistent with that of a recent study, which showed that PPAR-␣ activation stimulates both differentiation and fatty acid oxidation in adipocytes, resulting in decreased adipose tissue weight and adipocyte size [33]. The mechanisms by which Lactobacillus strains stimulate the PPAR-␣ gene expression in adipose tissue are partially known: one of the mechanisms is by production of octadecenoic acid and conjugated linoleic acid and or the bacterial cell component acting as a PPAR ligand [8,37]. Future studies should aim to elucidate the underlying mechanisms of the PPAR-␣-agonistic effects of L. kefiri DH5.…”

“…PPAR‐α has been used as a target of gene therapy for obesity and dyslipidemia, especially for synthetic agonists such as fibrates . However, emerging studies suggest that pre‐ and probiotics could act as effective PPAR‐α agonists . A recent study showed that the administration of PPAR‐α ‐agonistic probiotics L. amylovorus CP1563 for 12 weeks in the overweight and mildly obese individuals improved the adiposity and lipid and glucose metabolism with no adverse effects .…”

“…that pre-and probiotics could act as effective PPAR-␣ agonists [7,8]. A recent study showed that the administration of PPAR-␣-agonistic probiotics L. amylovorus CP1563 for 12 weeks in the overweight and mildly obese individuals improved the adiposity and lipid and glucose metabolism with no adverse effects [7].…”

Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study

“…Lactobacillus amylovorus CP1563 (CP1563) was originally isolated from human fecal specimens. CP1563 was selected as a strain with high ligand activity for peroxisome proliferator-activated receptor α (PPARα) [28], which plays a crucial role in controlling lipid metabolism, reducing adiposity, and improving hepatic steatosis [29]. Previous studies indicated that the effect of CP1563 on obesity prevention was augmented by the fragmentation of the bacterial cells [30].…”

Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell

“…It is likely that multiple mechanisms contribute to the formation of atherosclerosis, such as hyperlipemia, inflammation, and immunity. Recently, the role of peroxisome proliferator-activated receptors (PPARs) and sphingomyelin synthase (SMS) have received increased attention [1, 24,30]. PPARs are ligandactivated transcription factors, which belong to the nuclear receptor superfamily.…”