title: Induction of peroxisomes by butyrate-producing probiotics.
abstract: We previously found that peroxisomal biogenesis factor 11a (Pex11a) deficiency is associated with a reduction in peroxisome abundance and impaired fatty acid metabolism in hepatocytes, and results in steatosis. In the present study, we investigated whether butyrate induces Pex11a expression and peroxisome proliferation, and studied its effect on lipid metabolism. C57BL/6 mice fed standard chow or a high-fat diet (HFD) were treated with tributyrin, 4-phelybutyrate acid (4-PBA), or the butyrate-producing probiotics (Clostridium butyricum MIYAIRI 588 [CBM]) plus inulin (dietary fiber), and the body weight, white adipose tissue, serum triglycerides, mRNA expression, and peroxisome abundance were evaluated. Tributyrin or 4-PBA treatment significantly decreased body weight and increased hepatic mRNA expression of peroxisome proliferator-activated receptor-α (PPARα) and Pex11a. In addition, 4-PBA treatment increased peroxisome abundance and the expression of genes involved in peroxisomal fatty acid β-oxidation (acyl-coenzyme A oxidase 1 and hydroxysteroid [17-beta] dehydrogenase 4). CBM and inulin administration reduced adipose tissue mass and serum triglycerides, induced Pex11a, acyl-coenzyme A oxidase 1, and hydroxysteroid (17-beta) dehydrogenase 4 genes, and increased peroxisome abundance in mice fed standard chow or an HFD. In conclusion, elevation of butyrate availability (directly through administration of butyrate or indirectly via administration of butyrate-producing probiotics plus fiber) induces PPARα and Pex11a and the genes involved in peroxisomal fatty acid β-oxidation, increases peroxisome abundance, and improves lipid metabolism. These results may provide a new therapeutic strategy against hyperlipidemia and obesity.
authors: Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Huachun
authors: H
authors: Weng
authors: Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Kosuke
authors: K
authors: Endo
authors: Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Jiawei
authors: J
authors: Li
authors: Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Naoko
authors: N
authors: Kito
authors: Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
authors: Naoharu
authors: N
authors: Iwai
mesh_terms: D000818:Animals; D002087:Butyrates; D046972:Clostridium butyricum; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D007444:Inulin / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D047493:PPAR alpha / Q000096:biosynthesis; D020675:Peroxisomes / Q000378:metabolism*; D019936:Probiotics / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D008565:Membrane Proteins; D047493:PPAR alpha; C469727:Pex11alpha protein, mouse; D007444:Inulin