PMID- 32878262 OWN - NLM STAT- MEDLINE DCOM- 20210907 LR - 20210907 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 10 IP - 9 DP - 2020 Aug 31 TI - Branched-Chain Fatty Acids as Mediators of the Activation of Hepatic Peroxisome Proliferator-Activated Receptor Alpha by a Fungal Lipid Extract. LID - 10.3390/biom10091259 [doi] LID - 1259 AB - The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA. FAU - Maheshwari, Garima AU - Maheshwari G AD - Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. AD - Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. FAU - Ringseis, Robert AU - Ringseis R AUID- ORCID: 0000-0002-1321-4820 AD - Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Wen, Gaiping AU - Wen G AD - Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Gessner, Denise K AU - Gessner DK AUID- ORCID: 0000-0002-7934-1304 AD - Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. FAU - Rost, Johanna AU - Rost J AD - Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. FAU - Fraatz, Marco A AU - Fraatz MA AUID- ORCID: 0000-0002-5028-9653 AD - Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. FAU - Zorn, Holger AU - Zorn H AUID- ORCID: 0000-0002-8383-8196 AD - Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. AD - Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Str. 2, 35394 Giessen, Germany. FAU - Eder, Klaus AU - Eder K AD - Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. LA - eng GR - Insect Biotechnology and Bioresoursces/Hessisches Ministerium fur Wissenschaft und Kunst/International GR - ID 57243780/Deutscher Akademischer Austauschdienst/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200831 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Fatty Acids) RN - 0 (PPAR alpha) RN - 0 (Transcription Factors) RN - Conidiobolus heterosporus SB - IM MH - Animals MH - Cell Line, Tumor MH - Conidiobolus/*chemistry MH - Fatty Acids/*metabolism MH - Gene Expression Regulation MH - Genes, Reporter MH - PPAR alpha/agonists/*metabolism MH - Rats MH - Transcription Factors/*metabolism PMC - PMC7565516 OTO - NOTNLM OT - Conidiobolus heterosporus OT - branched-chain fatty acids OT - fatty acid oxidation OT - hepatocyte. OT - lipid metabolism OT - peroxisome proliferator-activated receptor alpha COIS- The authors declare no conflict of interest. EDAT- 2020/09/04 06:00 MHDA- 2021/09/08 06:00 PMCR- 2020/09/01 CRDT- 2020/09/04 06:00 PHST- 2020/06/08 00:00 [received] PHST- 2020/08/26 00:00 [revised] PHST- 2020/08/28 00:00 [accepted] PHST- 2020/09/04 06:00 [entrez] PHST- 2020/09/04 06:00 [pubmed] PHST- 2021/09/08 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - biom10091259 [pii] AID - biomolecules-10-01259 [pii] AID - 10.3390/biom10091259 [doi] PST - epublish SO - Biomolecules. 2020 Aug 31;10(9):1259. doi: 10.3390/biom10091259.