PMID- 37960348 OWN - NLM STAT- MEDLINE DCOM- 20231115 LR - 20231117 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 15 IP - 21 DP - 2023 Nov 6 TI - Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice. LID - 10.3390/nu15214696 [doi] LID - 4696 AB - A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4-6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-alpha protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-alpha in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-alpha, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action. FAU - Alvarez, Daniela AU - Alvarez D AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. FAU - Ortiz, Macarena AU - Ortiz M AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. FAU - Valdebenito, Gabriel AU - Valdebenito G AUID- ORCID: 0000-0002-7169-6653 AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. FAU - Crisosto, Nicolas AU - Crisosto N AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. AD - Endocrinology Unit, Department of Medicine, Clinica Alemana de Santiago, Faculty of Medicine, Universidad del Desarrollo, Santiago 7610658, Chile. FAU - Echiburu, Barbara AU - Echiburu B AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. FAU - Valenzuela, Rodrigo AU - Valenzuela R AUID- ORCID: 0000-0001-9298-6142 AD - Nutrition Department, School of Medicine, Universidad de Chile, Santiago 8380000, Chile. FAU - Espinosa, Alejandra AU - Espinosa A AUID- ORCID: 0000-0003-4779-5341 AD - Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380453, Chile. FAU - Maliqueo, Manuel AU - Maliqueo M AUID- ORCID: 0000-0003-3872-0217 AD - Laboratory of Endocrinology and Metabolism, Department of Internal Medicine West Division, Universidad de Chile, Santiago 8350499, Chile. LA - eng GR - FONDECYT 1181798/Agencia Nacional de Investigacion y Desarrollo/ GR - FONDECYT 1181774/Agencia Nacional de Investigacion y Desarrollo/ GR - FONDECYT 1201483/Agencia Nacional de Investigacion y Desarrollo/ GR - FONDECYT 1221098/Agencia Nacional de Investigacion y Desarrollo/ GR - CONICYT-PFCHA/Doctorado Nacional/2018-21181253/Agencia Nacional de Investigacion y Desarrollo/ PT - Journal Article DEP - 20231106 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Fatty Acids) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 0 (Peroxisome Proliferator-Activated Receptors) SB - IM MH - Mice MH - Female MH - Pregnancy MH - Male MH - Animals MH - *Fatty Acids/metabolism MH - *Diet, High-Fat/adverse effects MH - Docosahexaenoic Acids/pharmacology MH - Placenta/metabolism MH - Peroxisome Proliferator-Activated Receptors/metabolism MH - Mice, Inbred C57BL MH - Liver/metabolism PMC - PMC10649644 OTO - NOTNLM OT - docosahexaenoic acid OT - fetal liver OT - high-fat diet OT - maternal liver OT - placenta OT - pregnancy COIS- The authors declare no conflict of interest. EDAT- 2023/11/14 06:43 MHDA- 2023/11/15 06:43 PMCR- 2023/11/06 CRDT- 2023/11/14 02:19 PHST- 2023/10/04 00:00 [received] PHST- 2023/10/27 00:00 [revised] PHST- 2023/11/03 00:00 [accepted] PHST- 2023/11/15 06:43 [medline] PHST- 2023/11/14 06:43 [pubmed] PHST- 2023/11/14 02:19 [entrez] PHST- 2023/11/06 00:00 [pmc-release] AID - nu15214696 [pii] AID - nutrients-15-04696 [pii] AID - 10.3390/nu15214696 [doi] PST - epublish SO - Nutrients. 2023 Nov 6;15(21):4696. doi: 10.3390/nu15214696.