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Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner

Published online by Cambridge University Press:  23 January 2023

Nathalie Guriec
Affiliation:
Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France
Christelle Le Foll
Affiliation:
Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France
Jacques Delarue*
Affiliation:
Department of Nutritional Sciences, University Hospital/Faculty of Medicine/University of Brest, Brest, France ER 7479 SPURBO, University Hospital/Faculty of Medicine/University of Brest, Brest, France
*
*Corresponding author: Jacques Delarue, email jacques.delarue@univ-brest.fr

Abstract

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague–Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.

Type
Research Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

Present address: Institute of Veterinary Physiology, University of Zurich, CH-8057, Zurich, Switzerland.

References

WHO (2021) Obesity and Overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed 19 November 2022).Google Scholar
World Obesity (2022) World Obesity Atlas 2022. https://www.worldobesityday.org/assets/downloads/World_Obesity_Atlas_2022_WEB.pdf (accessed 19 November 2022).Google Scholar
IDF Diabetes Atlas (2022) Diabetes around the World in 2021. https://diabetesatlas.org (accessed 19 November 2022).Google Scholar
Roden, M & Shulman, GI (2019) The integrative biology of type 2 diabetes. Nature 576, 5160.CrossRefGoogle ScholarPubMed
Moreno-Fernandez, J, Ochoa, JJ, Lopez-Frias, M, et al. (2020) Impact of early nutrition, physical activity and sleep on the fetal programming of disease in the pregnancy: a narrative review. Nutrients 12, 3900.CrossRefGoogle ScholarPubMed
Fall, CHD & Kumaran, K (2019) Metabolic programming in early life in humans. Philos Trans R Soc Lond B Biol Sci 374, 20180123.CrossRefGoogle ScholarPubMed
Hieronimus, B & Ensenauer, R (2021) Influence of maternal and paternal pre-conception overweight/obesity on offspring outcomes and strategies for prevention. Eur J Clin Nutr 75, 17351744.CrossRefGoogle ScholarPubMed
Schoonejans, JM & Ozanne, SE (2021) Developmental programming by maternal obesity: lessons from animal models. Diabet Med 38, e14694.CrossRefGoogle ScholarPubMed
Menjivar, M & Zambrano, E (2020) Maternal interventions to prevent adverse fetal programming outcomes due to maternal malnutrition: evidence in animal models. Placenta 102, 4954.Google Scholar
Hughes, AN & Oxford, JT (2014) A lipid-rich gestational diet predisposes offspring to nonalcoholic fatty liver disease: a potential sequence of events. Hepat Med 6, 1523.Google ScholarPubMed
Mennitti, LV, Oliveira, JL, Morais, CA, et al. (2015) Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem 26, 99111.CrossRefGoogle ScholarPubMed
Christoforou, ER & Sferruzzi-Perri, AN (2020) Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress. Cell Mol Life Sci 77, 48614898.CrossRefGoogle ScholarPubMed
Taouis, M, Dagou, C, Ster, C, et al. (2002) n-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle. Am J Physiol Endocrinol Metab 282, E664E671.CrossRefGoogle ScholarPubMed
Delarue, J (2020) Are marine n-3 fatty acids protective towards insulin resistance? From cell to human. Proc Nutr Soc 6, 111.Google Scholar
Xia, Y, Wang, Y, Cui, M, et al. (2021) Efficacy of n-3 fatty acid supplementation on cardiovascular risk factors in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Ann Palliat Med 10, 64256437.CrossRefGoogle ScholarPubMed
Gao, L, Lin, L, Shan, N, et al. (2020) The impact of n-3 fatty acid supplementation on glycemic control in patients with gestational diabetes: a systematic review and meta-analysis of randomized controlled studies. J Matern Fetal Neonatal Med 33, 17671773.CrossRefGoogle ScholarPubMed
Jiang, L, Gao, C, Yan, P, et al. (2020) n-3 fatty acids plus vitamin for women with gestational diabetes or prediabetes: a meta-analysis of randomized controlled studies. J Matern Fetal Neonatal Med 35, 18.Google ScholarPubMed
Delpino, FM, Figueiredo, LM, da Silva, BGC, et al. (2021) n-3 supplementation and diabetes: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 62, 114.Google Scholar
Shrestha, N, Sleep, SL, Cuffe, JSM, et al. (2020) Role of n-6 and n-3 fatty acids in fetal programming. Clin Exp Pharmacol Physiol 47, 907915.CrossRefGoogle ScholarPubMed
Duttaroy, AK (2009) Transport of fatty acids across the human placenta: a review. Prog Lipid Res 48, 5261.CrossRefGoogle ScholarPubMed
Campbell, FM, Gordon, MJ & Dutta-Roy, AK (1996) Preferential uptake of long chain polyunsaturated fatty acids by isolated human placental membranes. Mol Cell Biochem 155, 7783.CrossRefGoogle ScholarPubMed
Hanebutt, FL, Demmelmair, H, Schiessl, B, et al. (2008) Long-chain polyunsaturated fatty acid (LC-PUFA) transfer across the placenta. Clin Nutr 27, 685693.CrossRefGoogle ScholarPubMed
Nishimura, RY, Barbieiri, P, Castro, GS, et al. (2014) Dietary polyunsaturated fatty acid intake during late pregnancy affects fatty acid composition of mature breast milk. Nutrition 30, 685689.CrossRefGoogle ScholarPubMed
Larqué, E, Pagán, A, Prieto, MT, et al. (2014) Placental fatty acid transfer: a key factor in fetal growth. Ann Nutr Metab 64, 247253.CrossRefGoogle ScholarPubMed
Demmelmair, H & Koletzko, B (2021) Perinatal polyunsaturated fatty acid status and obesity risk. Nutrients 13, 3882.CrossRefGoogle ScholarPubMed
Mark, PJ, Wyrwoll, CS, Zulkafli, IS, et al. (2014) Rescue of glucocorticoid-programmed adipocyte inflammation by n-3 fatty acid supplementation in the rat. Reprod Biol Endocrinol 12, 39.CrossRefGoogle ScholarPubMed
Bringhenti, I, Schultz, A, Rachid, T, et al. (2011) An early fish oil-enriched diet reverses biochemical, liver and adipose tissue alterations in male offspring from maternal protein restriction in mice. J Nutr Biochem 22, 10091014.CrossRefGoogle ScholarPubMed
Chicco, A, Creus, A, Illesca, P, et al. (2016) Effects of post-suckling n-3 polyunsaturated fatty acids: prevention of dyslipidemia and liver steatosis induced in rats by a sucrose-rich diet during pre- and post- natal life. Food Funct 7, 445454.CrossRefGoogle ScholarPubMed
Heerwagen, MJ, Stewart, MS, de la Houssaye, BA, et al. (2013) Transgenic increase in n-3/n-6 Fatty Acid ratio reduces maternal obesity- associated inflammation and limits adverse developmental programming in mice. PLoS One 8, e67791.CrossRefGoogle ScholarPubMed
Wang, DD, Wu, F, Zhang, LY, et al. (2021) Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice. J Nutr Biochem 89, 108578.CrossRefGoogle ScholarPubMed
Ibrahim, A, Basak, S, Ehtesham, NZ, et al. (2009) Impact of maternal dietary fatty acid composition on glucose and lipid metabolism in male rat offspring aged 105 d. Br J Nutr 102, 233241.CrossRefGoogle ScholarPubMed
Hussain, A, Nookaew, I, Khoomrung, S, et al. (2013) A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post-weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice. Acta Physiol 209, 220234.Google Scholar
Sardinha, FL, Fernandes, FS, Tavares do Carmo, MG, et al. (2013) Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring. Am J Physiol Regul Integr Comp Physiol 304, R313R320.CrossRefGoogle Scholar
Vahdaninia, M, Mackenzie, H, Dean, T, et al. (2018) The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis. Eur J Nutr 58, 25972613.Google ScholarPubMed
Meyer, DM, Brei, C, Bader, BL, et al. (2020) Evaluation of maternal dietary n-3 LCPUFA supplementation as a primary strategy to reduce offspring obesity: lessons from the INFAT trial and implications for future research. Front Nutr 7, 156.CrossRefGoogle ScholarPubMed
Amirani, E, Asemi, Z, Asbaghi, O, et al. (2020) The effects of n-3 fatty acids supplementation on metabolic status in pregnant women: a systematic review and meta-analysis of randomized controlled trials. J Diabetes Metab Disord 19, 16851699.CrossRefGoogle ScholarPubMed
Garmendia, ML, Casanello, P, Flores, M, et al. (2021) The effects of a combined intervention (docosahexaenoic acid supplementation and home-based dietary counseling) on metabolic control in obese and overweight pregnant women: the MIGHT study. Am J Obstet Gynecol 224, 526.e1526.e25.CrossRefGoogle ScholarPubMed
Maslova, E, Hansen, S, Strøm, M, et al. (2018) Fish intake in pregnancy and offspring metabolic parameters at age 9–16-does gestational diabetes modify the risk? Nutrients 10, 1534.CrossRefGoogle ScholarPubMed
Monthe-Dreze, C, Penfield-Cyr, A, Smid, MC, et al. (2018) Maternal pre-pregnancy obesity attenuates response to n-3 fatty acids supplementation during pregnancy. Nutrients 10, 1908.CrossRefGoogle ScholarPubMed
Alvarez, D, Muñoz, Y, Ortiz, M, et al. (2021) Impact of maternal obesity on the metabolism and bioavailability of polyunsaturated fatty acids during pregnancy and breastfeeding. Nutrients 13, 19.CrossRefGoogle Scholar
Pettersson, US, Waldén, TB, Carlsson, PO, et al. (2012) Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One 7, e46057.CrossRefGoogle ScholarPubMed
Shi, H & Clegg, DJ (2009) Sex differences in the regulation of body weight. Physiol Behav 97, 199204.CrossRefGoogle ScholarPubMed
Sharma, P & Agnihotri, N (2020) Fish oil and corn oil induced differential effect on beiging of visceral and subcutaneous white adipose tissue in high-fat-diet-induced obesity. J Nutr Biochem 84, 108458.CrossRefGoogle ScholarPubMed
Ukropec, J, Reseland, JE, Gasperikova, D, et al. (2003) The hypotriglyceridemic effect of dietary n-3 FA is associated with increased beta-oxidation and reduced leptin expression. Lipids 38, 10231029.CrossRefGoogle ScholarPubMed
Le Foll, C, Corporeau, C, Le Guen, V, et al. (2007) Long- chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from phosphatidylinositol 3'-kinase activity in rats. Am J Physiol Endocrinol Metab 292, E1223E1230.CrossRefGoogle ScholarPubMed
Nasu-Kawaharada, R, Nakamura, A, Kakarla, SK, et al. (2013) A maternal diet rich in fish oil may improve cardiac Akt-related signaling in the offspring of diabetic mother rats. Nutrition 29, 688692.CrossRefGoogle Scholar
Zheng, J, Xiao, X, Zhang, Q, et al. (2014) Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring. Int J Mol Sci 15, 1496714983.CrossRefGoogle ScholarPubMed
George, G, Draycott, SAV, Muir, R, et al. (2019) The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning. Sci Rep 9, 14173.CrossRefGoogle ScholarPubMed
Korotkova, M, Gabrielsson, B, Lönn, M, et al. (2002) Leptin levels in rat offspring are modified by the ratio of linoleic to α-linolenic acid in the maternal diet. J Lipid Res 43, 17431749.CrossRefGoogle ScholarPubMed
Rolls, BA, Gurr, MI, Van Duijvenvoorde, PM et al. (1986) Lactation in lean and obese rats: effect of cafeteria feeding and of dietary obesity on milk composition. Physiol Behavior 38, 185190.CrossRefGoogle ScholarPubMed
Priego, T, Sanchez, J, García, AP, et al. (2013) Maternal dietary fat affects milk fatty acid profile and impacts on weight gain and thermogenic capacity of suckling rats. Lipids 48, 481495.CrossRefGoogle ScholarPubMed
Shankar, K, Kang, P, Harrell, A, et al. (2010) Maternal overweight programs insulin and adiponectin signaling in the offspring. Endocrinology 151, 25772589.CrossRefGoogle ScholarPubMed
Bautista, CJ, Montaño, S, Ramirez, V, et al. (2016) Changes in milk composition in obese rats consuming a high-fat diet. Br J Nutr 115, 538546.CrossRefGoogle ScholarPubMed
Zambrano, E, Rodríguez-González, GL, Reyes-Castro, LA, et al. (2021) DHA supplementation of obese rats throughout pregnancy and lactation modifies milk composition and anxiety behavior of offspring. Nutrients 13, 4243.CrossRefGoogle ScholarPubMed
Sun, B, Purcell, RH, Terrillion, CE, et al. (2012) Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes 61, 28332841.CrossRefGoogle ScholarPubMed
Rostami, H, Samadi, M, Yuzbashian, E, et al. (2017) Habitual dietary intake of fatty acids is associated with leptin gene expression in subcutaneous and visceral adipose tissue of patients without diabetes. Prostaglandins Leukot Essent Fatty Acids 126, 4954.CrossRefGoogle ScholarPubMed
Ferezou-Viala, J, Roy, AF, Serougne, D, et al. (2007) Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring. Am J Physiol Regul Integr Comp Physiol 293, R1056R1062.CrossRefGoogle ScholarPubMed
Cheng, L, Hu, T, Shi, H, et al. (2020) DHA reduces hypothalamic inflammation and improves central leptin signaling in mice. Life Sci 257, 118036.CrossRefGoogle ScholarPubMed
Chang, GQ, Gaysinskaya, V, Karatayev, O, et al. (2008) Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 28, 1210712119.CrossRefGoogle ScholarPubMed
Schipper, L, Bouyer, K, Oosting, A, et al. (2013) Postnatal dietary fatty acid composition permanently affects the structure of hypothalamic pathways controlling energy balance in mice. Am J Clin Nutr 98, 13951401.CrossRefGoogle ScholarPubMed
Parra, D, Ramel, A, Bandarra, N, et al. (2008) A diet rich in long chain n-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss. Appetite 51, 676680.CrossRefGoogle Scholar
Howie, GJ, Deborah, M, Sloboda, DM, et al. (2013) Timing of maternal exposure to a High Fat diet and development of obesity and hyperinsulinemia in male rat offspring: same metabolic phenotype, different developmental pathways? J Nutr Metab 2013, 517384.CrossRefGoogle ScholarPubMed
Latouche, C, Heywood, SE, Henry, SL, et al. (2014) Maternal overnutrition program changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring. J Nutr 144, 237244.CrossRefGoogle ScholarPubMed
Storlien, LH, Kraegen, EW, Chisholm, DJ, et al. (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237, 885888.CrossRefGoogle ScholarPubMed
Podolin, DA, Gayles, EC, Wei, Y, et al. (1998) Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats. Am J Physiol 274, R840R848.Google Scholar
D’Alessandro, ME, Chicco, A & Lombardo, YB (2013) Fish oil reverses the altered glucose transporter, phosphorylation, insulin receptor substrate-1 protein level and lipid contents in the skeletal muscle of sucrose-rich diet fed rats. Prostaglandins Leukot Essent Fatty Acids 88, 171177.CrossRefGoogle ScholarPubMed
Neschen, S, Moore, I, Regittnig, W, et al. (2002) Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab 282, E395E401.CrossRefGoogle ScholarPubMed
Ramalingam, L, Menikdiwela, KR, Clevenger, S, et al. (2018) Maternal and postnatal supplementation of fish oil improves metabolic health of mouse male offspring. Obesity 26, 17401748.CrossRefGoogle ScholarPubMed
Matorras, R, Exposito, A, Ferrando, M, et al. (2020) Oocytes of women who are obese or overweight have lower levels of n-3 polyunsaturated fatty acids compared with oocytes of women with normal weight. Fertil Steril 113, 5361.CrossRefGoogle ScholarPubMed
Abodi, M, De Cosmi, V, Parazzini, F, et al. (2022) n-3 fatty acids dietary intake for oocyte quality in women undergoing assisted reproductive techniques: a systematic review. Eur J Obstet Gynecol Reprod Biol 275, 97105.CrossRefGoogle ScholarPubMed
Sferruzzi-Perri, AN & Camm, EJ (2016) The programming power of the placenta. Front Physiol 14, 33.Google Scholar
Calabuig-Navarro, V, Puchowicz, M, Glazebrook, P, et al. (2016) Effect of ω-3 supplementation on placental lipid metabolism in overweight and obese women. Am J Clin Nutr 103, 10641072.CrossRefGoogle ScholarPubMed
Jones, ML, Mark, PJ & Waddell, BJ (2014) Maternal dietary n-3 fatty acids and placental function. Reproduction 147, R14352.CrossRefGoogle ScholarPubMed
Amatruda, M, Ippolito, G, Vizzuso, S, et al. (2019) Epigenetic effects of n-3 LCPUFAs: a role in pediatric metabolic syndrome. Int J Mol Sci 29, 2118.CrossRefGoogle Scholar
Maude, H, Sanchez-Cabanillas, C & Cebola, I (2021) Epigenetics of hepatic insulin resistance. Front Endocrinol 12, 681356.CrossRefGoogle ScholarPubMed
Ibrahim, HIM (2022) Epigenetic regulation of obesity-associated type 2 diabetes. Medicina 58, 1366.CrossRefGoogle ScholarPubMed
Milagro, FI, Campión, J, García-Díaz, DF, et al. (2009) High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem 65, 19.CrossRefGoogle ScholarPubMed
Lomba, A, Martínez, JA, García-Díaz, DF, et al. (2010) Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters. Mol Genet Metab 101, 273278.CrossRefGoogle Scholar
Uriarte, G, Paternain, L, Milagro, FI, et al. (2013) Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats. J Physiol Biochem 69, 601611.CrossRefGoogle ScholarPubMed
Jump, DB (2008) n-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol 19, 242247.CrossRefGoogle ScholarPubMed
van Dijk, SJ, Peters, TJ, Buckley, M, et al. (2018) DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood. Int J Obes 42, 2835.CrossRefGoogle ScholarPubMed
Seki, Y, Suzuki, M, Guo, X, et al. (2017) In utero exposure to a high-fat diet programs hepatic hypermethylation and gene dysregulation and development of metabolic syndrome in male mice. Endocrinology 158, 28602872.CrossRefGoogle ScholarPubMed
Suter, MA, Ma, J, Vuguin, PM, et al. (2014) In utero exposure to a maternal high-fat diet alters the epigenetic histone code at genes involved in both metabolism and liver development in a murine model. Am J Obstet Gynecol 210, 463.e1463.e11.CrossRefGoogle Scholar
Li, Y, Xu, S, Giles, A, et al. (2011) Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J 25, 16641679.CrossRefGoogle ScholarPubMed
Rahman, M, Halade, GV, Bhattacharya, A, et al. (2009) The fat-1 transgene in mice increases antioxidant potential, reduces pro-inflammatory cytokine levels, and enhances PPAR- γ and SIRT-1 expression on a calorie restricted diet. Oxid Med Cell Longev 2, 307316.CrossRefGoogle ScholarPubMed
Burdge, GC & Lillycrop, KA (2014) Fatty acids and epigenetics. Curr Opin Clin Nutr Metab Care 17, 156161.CrossRefGoogle ScholarPubMed
Basak, S, Vilasagaram, S & Duttaroy, AK (2020) Maternal dietary deficiency of n-3 fatty acids affects metabolic and epigenetic phenotypes of the developing fetus. Prostaglandins Leukot Essent Fatty Acids 158, 102109.CrossRefGoogle ScholarPubMed
Basak, S & Duttaroy, AK (2022) Maternal PUFAs, placental epigenetics, and their relevance to fetal growth and brain development. Reprod Sci (Epublication ahead of print version 8 June 2022).CrossRefGoogle Scholar
McGregor, RA & Choi, MS (2011) microRNAs in the regulation of adipogenesis and obesity. Curr Mol Med 11, 304316.CrossRefGoogle ScholarPubMed
Ramaiyan, B & Talahalli, RR (2018) Dietary unsaturated fatty acids modulate maternal dyslipidemia-induced DNA methylation and histone acetylation in placenta and fetal liver in rats. Lipids 53, 581588.CrossRefGoogle ScholarPubMed
van Dijk, SJ, Zhou, J, Peters, TJ, et al. (2016) Effect of prenatal DHA supplementation on the infant epigenome: results from a randomized controlled trial. Clin Epigenet 8, 114.CrossRefGoogle ScholarPubMed
Hao, L, Nie, YH, Chen, CY, et al. (2022) n-3 polyunsaturated fatty acids protect against high-fat diet-induced morphological and functional impairments of brown fat in transgenic fat-1 mice. Int J Mol Sci 23, 11903.CrossRefGoogle ScholarPubMed
Tsuji, T, Bussberg, V, MacDonald, AM, et al. (2022) Transplantation of brown adipose tissue with the ability of converting n-6 to n-3 polyunsaturated fatty acids counteracts high-fat-induced metabolic abnormalities in mice. Int J Mol Sci 23, 5321.CrossRefGoogle Scholar
Fan, R, Toney, AM, Jang, Y et al. (2018) Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice. Biochim Biophys Acta, Mol Cell Biol Lipids 1863, 14881497.CrossRefGoogle ScholarPubMed
Yue, H, Liu, W, Zhang, W, et al. (2021) Dietary low ratio of n-6/n-3 polyunsaturated fatty acids improve type 2 diabetes mellitus via activating brown adipose tissue in male mice. J Food Sci 86, 10581065.CrossRefGoogle ScholarPubMed
Wei, W, Hu, M, Huang, J, et al. (2021) Anti-obesity effects of DHA and EPA in high fat-induced insulin resistant mice. Food Funct 12, 16141625.CrossRefGoogle ScholarPubMed