Placental Adaptations to Maternal Nutritional Insults as Targets Against the Obesity Epidemic

Автор(и)

DOI:

https://doi.org/10.54548/njps.v40i2.1

Ключові слова:

Maternal obesity, intervention, Nutrition, Placenta, DOHaD, developmental programming

Анотація

The worldwide obesity epidemic presents a considerable public health and economic challenge globally. While lifestyle and genetic predisposition are recognized obesogenic factors, compelling evidence indicates that maternal nutritional "insults" (MNI) occurring before pregnancy, during pregnancy, or during lactation predispose the offspring to obesity and other cardiometabolic disorders in adulthood. This phenomenon termed developmental origins of health and disease (DOHaD) can be utilized to formulate intervention strategies aimed at counteracting the developmental programming of obesity in subsequent generations. The placenta, a temporary organ of pregnancy, experiences adaptive changes in response to MNI. Alterations in placental secretory functions, morphology, and gene expression profiles influence foetal metabolic pathways. The mechanisms through which placental adaptations influence developmental programming present a distinct opportunity to pinpoint targets in combating the increasing prevalence of obesity. Clinical and experimental studies have clarified various underlying mechanisms, including modified placental metabolic regulation, oxidative stress, inflammation, immune dysregulation, and epigenetic alterations, offering insights for the formulation of effective intervention strategies. This review encapsulates placental adaptive responses to MNI, elucidates the underlying mechanisms, explores potential placental intervention strategies, and identifies areas for future research.

Посилання

Alfaradhi, M. Z., & Ozanne, S. E. (2011). Developmental programming in response to maternal overnutrition. Frontiers in Genetics, 2, 27. https://doi.org/10.3389/fgene.2011.00027

Anderson, C. M., & Stahl, A. (2013). SLC27 fatty acid transport proteins. Molecular Aspects of Medicine, 34, 516-528.

Aye, I. L., & Keelan, J. A. (2013). Placental ABC transporters, cellular toxicity and stress in pregnancy. Chemico-Biological Interactions, 203, 456-466.

Barbour-Tuck, E., Erlandson, M., Muhajarine, N., Foulds, H., & Baxter-Jones, A. (2018). Influence of Childhood and Adolescent Fat Development on Fat Mass Accrual During Emerging Adulthood: A 20-Year Longitudinal Study. Obesity, 26(3), 613–620. https://doi.org/10.1002/oby.22111.

Barker, D. J. P. (1998). In utero programming of chronic disease. Clinical Science, 95(2), 115–128.

Barker, D. J. (1995). The foetal and infant origins of disease. European Journal of Clinical Investigation, 25, 457-463.

Bayer, A., Lennemann, N. J., Ouyang, Y., Bramley, J. C., Morosky, S., Marques, E. T. Jr., Coyne, C. B. (2016). Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host & Microbe, 19(5), 705-712.

Bayol, S. A., Farrington, S. J., & Stickland, N. C. (2007). A maternal “junk food” diet in pregnancy and lactation promotes an exacerbated taste for “junk food” and a greater propensity for obesity in rat offspring. British Journal of Nutrition, 98(4), 843–851.

Beeson, J. H., Blackmore, H. L., Carr, S. K., et al. (2018). Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring. Molecular Metabolism, 16, 35–44.

Bell, A. W., & Ehrhardt, R. A. (2002). Regulation of placental nutrient transport and implications for foetal growth. Nutrition Research Reviews, 15, 211–230.

Blackmore, H. L., Niu, Y., Fernandez-Twinn, D. S., Tarry-Adkins, J. L., Giussani, D. A., & Ozanne, S. E. (2014). Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight. Endocrinology, 155(10), 3970–3980.

Blackmore, H. L., & Ozanne, S. E. (2015). Programming of cardiovascular disease across the life-course. Journal of Molecular and Cellular Cardiology, 83, 122–130.

Braun, T., Challis, J. R. G., Newnham, J. P., & Sloboda, D. M. (2022). Early-life glucocorticoid exposure: The hypothalamic-pituitary-adrenal axis, placental function, and developmental origins of health and disease. Journal of Developmental Origins of Health and Disease, 13(1), 22–33.

Burton, G. J., & Fowden, A. L. (2015). The placenta: A multifaceted, transient organ. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1663), 20140066.

Catalano, P. M. (2003). Obesity and pregnancy - The propagation of a vicious cycle? Journal of Clinical Endocrinology and Metabolism, 88(8), 3505–3506.

Chang, E., Hafner, H., Varghese, M., et al. (2019). Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation. Scientific Reports, 9(1), 16027. https://doi.org/10.1038/s41598-019-52583-x.

Chooi, Y. C., Ding, C., & Magkos, F. (2019). The epidemiology of obesity. Metabolism, 92, 6–10.

Cross, J. C. (2005). How to make a placenta: Mechanisms of trophoblast cell differentiation in mice – a review. Placenta, 26 Suppl A, S3–S9.

Cureton, N., Kirka, K., Nair, A., et al. (2017). Bioengineering strategies for advancing maternal-foetal medicine. Advanced Drug Delivery Reviews, 116, 124–139.

Dearden, L., Buller, S., Furigo, I. C., Fernandez-Twinn, D. S., & Ozanne, S. E. (2020). Maternal obesity causes foetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways. Molecular Metabolism, 42, 101079. https://doi.org/10.1016/j.molmet.2020.101079.

Diaz, P., Harris, J., Rosario, F. J., Powell, T. L., & Jansson, T. (2015). Increased placental fatty acid transporter 6 and binding protein 3 expression and foetal liver lipid accumulation in a mouse model of obesity in pregnancy. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 309, R1569–R1577.

Diaz, P., Harris, J., Rosario, F. J., Powell, T. L., & Jansson, T. (2023). Placental fatty acid transporter expression and epigenetic regulation in response to maternal obesity. American Journal of Physiology – Endocrinology and Metabolism, 324(2), E123–E133. https://doi.org/10.1152/ajpendo.00345.2022.

Driscoll, A. K., & Gregory, E. C. W. (2021). Prepregnancy body mass index and infant outcomes by race and Hispanic origin: United States, 2020. National Vital Statistics Reports, 70(16), 1–8.

Ebenbichler, C. F., Kaser, S., Tilg, H., et al. (2002). Glucose stimulates the expression of the leptin gene in human trophoblast. Placenta, 23 Suppl A, S154-S161.

European Commission. (2019). Overweight and obesity - BMI statistics. Open Research Europe. (Data retrieved 2019 from Eurostat).

Fang, J., Yang, J., Xiao, H., et al. (1997). Tumor necrosis factor α delays insulin receptor recycling in the placenta: Mechanism of insulin resistance in pregnancy. The Journal of Clinical Investigation, 100(3), 439-449.

Fass, S., & De Vos, P. (2018). Maternal obesity and adipocyte dysfunction in the placenta: Potential consequences for the mother and baby. Placenta, 69, 134-139.

Fernandez-Jimenez, N., Castellano-Castillo, D., Diaz-Ruiz, A., et al. (2022). Epigenetics and adipose tissue: Key mechanisms in the development of metabolic diseases and potential therapeutic targets. Frontiers in Physiology, 13, 822205.

Ferey, J. L. A., Boudoures, A. L., Reid, M., et al. (2019). A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance. American Journal of Physiology – Heart and Circulatory Physiology, 316 (5), H1202–H1210.

Ganguly, E., Hula, N., Spaans, F., Cooke, C. M., & Davidge, S. T. (2020). Placenta-targeted treatment strategies: An opportunity to impact foetal development and improve offspring health later in life. Pharmacological Research, 157, 104836.

Ganguly, E., & Sferruzzi-Perri, A. N. (2020). The role of the placenta in foetal programming of adult health and disease. Frontiers in Physiology, 11, 40.

Goulopoulou, S., & Davidge, S. T. (2015). Molecular mechanisms of maternal vascular dysfunction in preeclampsia. Trends in Molecular Medicine, 21(2), 88-97.

Gomez-Vilarrubla, A., Burgueño, A. L., Fernandez-Veledo, S., & Vendrell, J. (2023). Placental epigenetics in obesity and gestational diabetes mellitus. Diabetologia, 66(3), 415-429.

Hachul, A. C. B., Pauli, L. S. S., Becker, M. A., et al. (2018). Green tea extract during pregnancy increases glucose tolerance in adult offspring, but litter’s postnatal high-fat diet exacerbates adiposity regardless of maternal diet. Diabetology & Metabolic Syndrome, 10, 82.

Haghiac, M., Yang, X. H., Presley, L., et al. (2015). Dietary omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: A randomized double-blind controlled clinical trial. PLoS ONE, 10(9), e0137309.

Hales, C. N., & Barker, D. J. (2001). The thrifty phenotype hypothesis. British Medical Bulletin, 60, 5-20.

Harris, L. K. (2016). Review: Trophoblast-vascular cell interactions in early pregnancy: How to remodel a vessel. Placenta, 48 Suppl A, S13-S21.

Hellmuth, C., Lindsay, K. L., Uhl, O., et al. (2017). Association of maternal prepregnancy BMI with metabolomic profile across gestation. International Journal of Obesity, 41(1), 159-169.

Hjort, L., Novakovic, B., & Saffery, R. (2022). Placental DNA methylation in gestational diabetes and future metabolic disease for the child. Current Diabetes Reports, 22(7), 255-262.

Holtan, S. G., Creedon, D. J., Haluska, P., & Markovic, S. N. (2009). Cancer and pregnancy: Parallels in growth, invasion, and immune modulation and implications for cancer therapeutic agents. Mayo Clinic Proceedings, 84(11), 985-1000.

Howell, K. R., & Powell, T. L. (2017). Effects of maternal obesity on placental function and foetal development. Reproduction, 153 (3), R97-R108.

Howie, G. J., Sloboda, D. M., Kamal, T., & Vickers, M. H. (2009). Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. Journal of Physiology, 587(4), 905–915.

Inoue, Y., Qin, B., Poti, J., Sokol, R., & Gordon-Larsen, P. (2018). Epidemiology of obesity in adults: Latest trends. Current Obesity Reports, 7(4), 276–288.

Isesele, P. O., Lagoda, C., Fan, W., et al. (2022). Fish oil inhibits fatty acid metabolism gene expression in human placenta and adipose tissue. Journal of Clinical Endocrinology & Metabolism, 107(6), e2488–e2499.

Isganaitis, E., Woo, M., Ma, H., et al. (2014). Developmental programming by maternal insulin resistance: Hyperinsulinemia, glucose intolerance, and dysregulated lipid metabolism in male offspring of insulin-resistant mice. Diabetes, 63(2), 688–700.

James-Allan, L. B., Rosario, F. J., Barner, K., et al. (2019). Regulation of placental amino acid transport by maternal obesity in the baboon. American Journal of Physiology - Endocrinology and Metabolism, 317(5), E1020–E1029.

Jin, L., Feng, X., Rong, H., et al. (2018). The antiproliferative effect of curcumin against TGF-β-induced human adipocyte differentiation is associated with AMPKα-dependent activation of the ERK1/2 signaling pathway. Food & Function, 9(10), 5883–5894.

Kearns, M. L., & Reynolds, C. M. (2024). Developmentally programmed obesity: Is there a role for anti-inflammatory nutritional strategies? Experimental Physiology, 109 (4), 633–646.

Kelly, A. C., Powell, T. L., & Jansson, T. (2020). Placental function in maternal obesity. Clinical Science, 134(8), 961–984.

King, A., Ndifon, C., Lui, S., Widdows, K., Abell, K. J., et al. (2016). Tumor-homing peptides as tools for targeted delivery of payloads to the placenta. Science Advances, 2(5), e1600349.

Knipp, G. T., Liu, B., Audus, K. L., Fujii, H., Ono, T., & Soares, M. J. (2000). Fatty acid transport regulatory proteins in the developing rat placenta and in trophoblast cell culture models. Placenta, 21(4), 367–375.

Knofler, M., Haider, S., Saleh, L., et al. (2019). Human placenta and trophoblast development: Key molecular mechanisms and model systems. Cellular and Molecular Life Sciences, 76(18), 3479–3496.

Kreis, N. N., Ritter, A., Louwen, F., & Yuan, J. (2020). A message from the human placenta: Structural and immunomodulatory defense against SARS-CoV-2. Cells, 9(8), 1777.

Lager, S., & Powell, T. L. (2012). Regulation of nutrient transport across the placenta. Journal of Pregnancy, 179827.

Lager, S., Gilbert, J. S., & Benediktsson, R. (2011). Placental nutrient transport capacity and foetal growth in pregnancies complicated by maternal obesity. Placenta, 32(1), 77–82.

Laskewitz, A., Hollander, M. H. J., Schuiling-Veninga, C. C. M., & Ganzevoort, W. (2019). Placental macrophage polarization in preeclampsia: A systematic review. Hypertension in Pregnancy, 38(4), 202-209.

Lean, S. C., Heazell, A. E. P., Dilworth, M. R., Mills, T. A., & Jones, R. L. (2017). Placental dysfunction underlies increased risk of foetal growth restriction and stillbirth in advanced maternal age women. Scientific Reports, 7, 9677.

Li, J., Li, C., Liang, Z., et al. (2018). Dietary polyphenols as potential nutraceuticals in management of diabetes: Mechanistic aspects. Food & Function, 9(12), 6056–6082.

Li, J., Huang, J., Li, J., et al. (2012). Green tea polyphenols ameliorate adipose insulin resistance by improving oxidative stress in high fat diet-fed mice. Nutrition Research, 32(6), 408–417.

Liong, S., Lappas, M., Yong, H. E., et al. (2018). Protein O-GlcNAcylation is increased in human term placentae from gestational diabetes mellitus and modulates inflammatory pathways. Placenta, 66, 36-44.

Louwen, F., Kreis, N. N., Ritter, A., & Yuan, J. (2018). Insight into the development of obesity: Functional alterations of adipose-derived mesenchymal stem cells. Obesity Reviews, 19(7), 888–904.

Louwen, F., Kreis, N. N., Ritter, A., & Yuan, J. (2024). Maternal obesity and placental function: Impaired maternal–foetal axis. Archives of Gynecology and Obstetrics, 309(6), 2279–2288.

Lucas, A. (2000). Programming not metabolic imprinting. American Journal of Clinical Nutrition, 71(3), 602. (Letter).

Malti, N., Laforest, F., & Bougnères, P. (2014). Maternal and foetal nitric oxide and antioxidant enzymes in a rat model of diet-induced obesity. The Journal of Maternal-Foetal & Neonatal Medicine, 27(17), 1809–1813.

Martino, J., Sebert, S., Segura, M. T., et al. (2016). Maternal body weight and gestational diabetes differentially influence placental and pregnancy outcomes. Journal of Clinical Endocrinology & Metabolism, 101(1), 59–68.

Mele, J., Mikhailidis, D. P., & Ntzeros, A. (2014). Maternal obesity during pregnancy and foetal metabolism. Journal of Developmental Origins of Health and Disease, 5(6), 451–458.

Myles, I. A., & Datta, S. K. (2013). Toll-like receptor 2 in tolerance and immunity. Biochemical Society Transactions, 41(1), 232–237.

Myatt, L., & Maloyan, A. (2016). Obesity and placental function. Seminars in Reproductive Medicine, 34(1), 42–49.

Neumann, J., Rose-Sperling, D., & Hellmich, U. A. (2017). Diverse relations between ABC transporters and lipids: An overview. Biochimica et Biophysica Acta (BBA)- Biomembranes, 1859(4), 605–618.

Nogues, M. A., Dos Santos, E., Moyon, T., & Vaiman, D. (2019). The placenta in maternal obesity. International Journal of Developmental Biology, 63(2), 141–153.

Ogunsola O. A., Arikawe A. P. (2014). Effects of fructose feeding on maternal and amniotic fluid corticotropin releasing hormone and C - reactive protein in pregnant female Sprague-Dawley rats. Journal of African Association of Physiological Sciences, 2(1): 47 - 55.

Ogunsola, O. A., Arikawe, A. P., Iranloye, B. O., & Adegoke, O. A. (2019). Maternal serum progesterone levels and placental expression of progesterone receptors in insulin-resistant pregnant rats. Journal of the African Association of Physiological Sciences, 7(2), 97-108.

Olney, R. C., Zerbato, V., & King, R. G. (2022). Exposure to a maternal high-fat diet alters the foetal liver transcriptome in nonhuman primates. American Journal of Physiology – Endocrinology and Metabolism, 323(4), E557-E568.

Ounjaijean, S., Phupong, V., & Rattanasiri, S. (2021). Western fast-food consumption and overweight status in Thai adolescents. BMC Public Health, 21(1), 1326.

Panahi, Y., Khalili, N., Hosseini, M. S., et al. (2016). Curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: A randomized controlled trial. Journal of Cardiovascular Pharmacology, 68(3), 223–229.

Pantham, P., Aye, I. L., & Powell, T. L. (2015). Inflammation in maternal obesity and gestational diabetes: Placental mechanisms and therapeutic approaches. Placenta, 36(7), 709-715.

Peng, W., Li, K., Zhang, W., et al. (2021). Anti-inflammatory effects of curcumin in the pregnancy complications: Pre-eclampsia, preterm birth, and foetal growth restriction. Drug Design, Development and Therapy, 15, 3973–3986.

Phillips, T. J., Scott, H., Menassa, D. A., et al. (2017). Treating the placenta to prevent adverse effects of gestational hypoxia on foetal brain development. Scientific Reports, 7(1), 9079.

Poston, L., Caleyachetty, R., Cnattingius, S., et al. (2016). Preconceptional and maternal obesity: Epidemiology and health consequences. The Lancet Diabetes & Endocrinology, 4(12), 1025-1036.

Ramalingam, M., Hwang, I., You, S., & Lee, J. (2021). Fish oil supplementation mitigates maternal obesity-induced metabolic complications in female offspring. Endocrine Journal, 68(6), 681-694.

Renshall, L. J., Cottrell, E. C., Cowley, E., et al. (2020). Antenatal sildenafil treatment increases offspring blood pressure in the placental-specific Igf2 knockout mouse model of foetal growth restriction. American Journal of Physiology - Heart and Circulatory Physiology, 318(2), H252-H263.

Rodgers, A., & Sferruzzi-Perri, A. N. (2021). Developmental programming of offspring adipose tissue biology and obesity risk. International Journal of Obesity, 45(6), 1170-1192.

Ros, P., Vázquez, C. M., Cabrerizo, L., et al. (2018). Dietary resveratrol improves cardiovascular health of adult male offspring exposed to maternal obesity. International Journal of Obesity, 42(1), 39-49.

Rosario, F. J., Kanai, Y., Powell, T. L., & Jansson, T. (2020). Increased placental fatty acid transport and foetal fat deposition in obese pregnancies: A role for FATP2 and FATP6. American Journal of Physiology - Endocrinology and Metabolism, 319(3), E507-E515.

Rosario, F. J., Dimasuay, K. G., Kanai, Y., Powell, T. L., & Jansson, T. (2016a). Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2. Clinical Science, 130(7), 499–512.

Rosario, F. J., Powell, T. L., & Jansson, T. (2016b). Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating cell surface FR-α and RFC. Scientific Reports, 6, 31705.

Rosario, F. J., Kanai, Y., Powell, T. L., & Jansson, T. (2015). Increased placental nutrient transport in a novel mouse model of maternal obesity with foetal overgrowth. Obesity, 23(8), 1663–1670.

Salvatore Lacagnina, D. O. (2019). The developmental origins of health and disease (DOHaD). American Journal of Lifestyle Medicine, 14(1), 47–50.

Satokar, V. V., Shende, V. S., Momin, A. A., & Desai, M. (2023). Maternal fish oil supplementation prevents high-fructose-induced metabolic disturbances in rat dams and their offspring. Journal of Nutrition, 153(4), 1152–1165.

Scheja, L., & Heeren, J. (2019). The endocrine function of adipose tissues in health and cardiometabolic disease. Nature Reviews Endocrinology, 15(9), 507–524.

Schoonejans, J. M., & Ozanne, S. E. (2021). Developmental programming by maternal obesity: Lessons from animal models. Diabetic Medicine, 38(6), e14694.

Shirasuna, K., Karasawa, T., Takano, T., & Iwata, H. (2016). Maternal obesity and obesity-related metabolic disorders cause placental hypoxia and oxidative stress. Reproduction, 152(6), 593–605.

Shrestha, N., Ezechukwu, H. C., Holland, O. J., & Hryciw, D. H. (2020). Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 319(4), R507–R516.

Sibley, C. P. (2009). Understanding placental nutrient transfer – why bother? New biomarkers of foetal growth. Journal of Physiology, 587(14), 3431–3440.

Simmons, D. G., & Cross, J. C. (2005). Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Developmental Biology, 284(1), 12–24.

Simmons, D. G., Fortier, A. L., & Cross, J. C. (2007). Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Developmental Biology, 304(2), 567–578.

Sood, R., Zehnder, J. L., Druzin, M. L., & Brown, P. O. (2006). Gene expression patterns in human placenta. Proceedings of the National Academy of Sciences USA, 103(14), 5478–5483.

Stanford, K. I., Lee, M. Y. Y., Getchell, K. M., et al. (2015). Exercise before and during pregnancy prevents the deleterious effects of maternal high-fat feeding on metabolic health of male offspring. Diabetes, 64(2), 427–433.

Taylor, P. D., McConnell, J., Khan, I. Y., et al. (2005). Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 288(1), R134-R139.

Thaete, L. G., Qu, X. W., Jilling, T., et al. (2013). Impact of Toll-like receptor 4 deficiency on the response to uterine ischemia/reperfusion in mice. Reproduction, 145(5), 517-526.

Tran, M., Tam, W., Xiao, J., & McIntyre, H. D. (2017). The effects of resveratrol on vascular inflammation in human gestational diabetes: A pilot randomized controlled trial. Reproductive Sciences, 24(3), 494-504.

Turco, M. Y., & Moffett, A. (2019). Development of the human placenta. Development, 146(22), dev163428.

Vaughan, O. R., & Fowden, A. L. (2016). Placental metabolism: Substrate requirements and the response to stress. Reproduction in Domestic Animals, 51 Suppl 2, 25-35.

Vaughan, O. R., Sferruzzi-Perri, A. N., & Fowden, A. L. (2017). Maternal corticosterone regulates nutrient allocation to foetal tissues in the mouse. Journal of Physiology, 595(15), 4763-4774.

World Health Organization. (2020). Obesity and overweight (fact sheet). World Health Organization. Retrieved 2020, from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.

World Health Organization. (2024). Controlling the global obesity epidemic. World Health Organization. Retrieved 2024, from https://www.who.int/activities/controlling-the-global-obesity-epidemic.

Yang, X., Li, M., Haghiac, M., Catalano, P. M., O’Tierney-Ginn, P., & Hauguel-de Mouzon, S. (2016). Causal relationship between obesity-related traits and TLR4-driven responses at the maternal–foetal interface. Diabetologia, 59 (12), 2459-2466.

Yokomizo, H., Inoguchi, T., Sonoda, N., et al. (2014). Maternal high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice. American Journal of Physiology - Endocrinology and Metabolism, 306 (10), E1163-E1175.

Zhou, J., Chen, J., Zhang, L., et al. (2018). Resveratrol suppresses obesity and metabolic dysfunction through activation of AMP-activated protein kinase (AMPK) and downregulation of Akt. Clinical Nutrition, 37 (2), 443-450.

Завантаження

Опубліковано

2025-12-31

Номер

Розділ

Review Articles

Схожі статті

1-10 з 38

Ви також можете розпочати розширений пошук схожих статей для цієї статті.