TitleMaternal Fat-1 Transgene Protects Offspring from Excess Weight Gain, Oxidative Stress, and Reduced Fatty Acid Oxidation in Response to High-Fat Diet.
Publication TypeJournal Article
Year of Publication2020
AuthorsBoyle, KE, Magill-Collins, MJ, Newsom, SA, Janssen, RC, Friedman, JE
Date Published03/2020
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Diet, High-Fat, Fatty Acid Desaturases, Female, Male, Maternal Exposure, Mice, Mice, Transgenic, Obesity, Oxidative Stress, Pregnancy, Transgenes

Overweight and obesity accompanies up to 70% of pregnancies and is a strong risk factor for offspring metabolic disease. Maternal obesity-associated inflammation and lipid profile are hypothesized as important contributors to excess offspring liver and skeletal muscle lipid deposition and oxidative stress. Here, we tested whether dams expressing the fat-1 transgene, which endogenously converts omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acid, could protect wild-type (WT) offspring against high-fat diet induced weight gain, oxidative stress, and disrupted mitochondrial fatty acid oxidation. Despite similar body mass at weaning, offspring from fat-1 high-fat-fed dams gained less weight compared with offspring from WT high-fat-fed dams. In particular, WT males from fat-1 high-fat-fed dams were protected from post-weaning high-fat diet induced weight gain, reduced fatty acid oxidation, or excess oxidative stress compared with offspring of WT high-fat-fed dams. Adult offspring of WT high-fat-fed dams exhibited greater skeletal muscle triglycerides and reduced skeletal muscle antioxidant defense and redox balance compared with offspring of WT dams on control diet. Fat-1 offspring were protected from the reduced fatty acid oxidation and excess oxidative stress observed in offspring of WT high-fat-fed dams. These results indicate that a maternal fat-1 transgene has protective effects against offspring liver and skeletal muscle lipotoxicity resulting from a maternal high-fat diet, particularly in males. Altering maternal fatty acid composition, without changing maternal dietary composition or weight gain with high-fat feeding, may highlight important strategies for n-3-based prevention of developmental programming of obesity and its complications.

Alternate JournalNutrients
PubMed ID32183350
PubMed Central IDPMC7146584
Grant ListDK062155 / NH / NIH HHS / United States
DK089743 / NH / NIH HHS / United States
HD057022 / NH / NIH HHS / United States
DK095509 / NH / NIH HHS / United States
DK048520 / NH / NIH HHS / United States
TL1-RR-025778 / / Colorado Clinical and Translational Sciences Institute /
AHA-11PRE5020014 / / American Heart Association /