Relationship between branched-chain amino acids and mother-offspring overweight/obesity transmission

FANG Chunli; ZHANG Zhihong; LIU Mengjiao

doi:10.11852/zgetbjzz2024-0937

PDF(631 KB)

Chinese Journal of Child Health Care ›› 2025, Vol. 33 ›› Issue (9) : 992-996. DOI: 10.11852/zgetbjzz2024-0937

Review

Relationship between branched-chain amino acids and mother-offspring overweight/obesity transmission

FANG Chunli^1,2, ZHANG Zhihong^1,2, LIU Mengjiao^1,2

Author information +

History +

Abstract

The escalating prevalence of childhood overweight and obesity may stem from the intergenerational transmission of maternal overweight and obesity.Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids involved in energy metabolism and protein synthesis.While BCAAs are closely associated with the risk of overweight and obesity, their role in mother-offspring intergenerational transmission remains unclear. Studies indicate that obese pregnant women exhibit elevated BCAA levels, which can be transferred to the fetus via placental transport.This process activates the mammalian target of rapamycin complex 1 (mTORC1), upregulating the expression of amino acid transporters and further facilitating fetal BCAAs uptake.Excessive BCAAs may disrupt glucose and lipid metabolism by promoting lipogenesis and impairing insulin signaling, thereby increasing offspring obesity risk.Given the critical role of BCAAs in the intergenerational transmission of obesity, this review synthesizes current evidence and mechanistic insights into the relationship between BCAAs and mother-offspring overweight/obesity transmission, in order to explore their potential as an intervention target and provide a scientific foundation for childhood obesity prevention strategies.

Key words

branched-chain amino acids / overweight / obesity / mother and infant / intergenerational transmission

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

FANG Chunli, ZHANG Zhihong, LIU Mengjiao. Relationship between branched-chain amino acids and mother-offspring overweight/obesity transmission[J]. Chinese Journal of Child Health Care. 2025, 33(9): 992-996 https://doi.org/10.11852/zgetbjzz2024-0937

References

[1] WHO.Obesity and overweight[EB/OL].(2024-03-01)[2024-09-30].https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
[2] NCD Risk Factor Collaboration (NCD-RisC).Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3 663 population-representative studies with 222 million children, adolescents, and adults[J].Lancet (London, England),2024,403(10431):1027-1050.
[3] 董彦会,陈力,刘婕妤,等.1985—2019年中国7~18岁儿童青少年超重与肥胖的流行趋势及预测研究[J].中华预防医学杂志,2023,57(4): 461-469.
Dong YH, Chen L, Liu JY, et al.Epidemiology and prediction of overweight and obesity among children and adolescents aged 7-18 years in China from 1985 to 2019[J].Chin J Prev Med, 2023,57(4): 461-469.(in Chinese)
[4] Yuan C, Dong Y, Chen H, et al.Determinants of childhood obesity in China[J].Lancet Public Health,2024, 9(12):e1105-e1114.
[5] Heslehurst N, Vieira R, Akhter Z, et al.The association between maternal body mass index and child obesity: A systematic review and meta-analysis[J].PLoS Med, 2019,16(6): e1002817.
[6] 陈霞, 袁云兰, 张焱, 等.孕前超重肥胖者妊娠期增重过度对妊娠结局和新生儿情况的影响[J].上海预防医学,2024,36(3): 255-261.
Chen X, Yuan YL, Zhang Y,et al.Impact excessive weight gain during pregnancy in women with pre-pregnancy overweight or obesity on pregnancy outcomes and neonatal conditions[J].Shanghai J Prev Med, 2024, 36(3): 255-261.(in Chinese)
[7] Skytte HN, Roland MCP, Christensen JJ,et al.Maternal metabolic profiling across body mass index groups: An exploratory longitudinal study[J].Acta Obstet Gynecol Scand,2024,103(3): 540-550.
[8] Bugajska J, Berska J, Wójcik M, et al.Amino acid profile in overweight and obese prepubertal children, can simple biochemical tests help in the early prevention of associated comorbidities?[J].Front Endocrinol (Lausanne),2023,14: e1412740.
[9] White PJ, Newgard CB.Branched-chain amino acids in disease[J].Science,2019,363(6424):582-583.
[10] Naofumi Y,Tomoya Y,Tatsunori O, et al.Bacteroides spp.promotes branched-chain amino acid catabolism in brown fat and inhibits obesity[J].iScience,2021,24(11):103342.
[11] Lischka J, Schanzer A, Hojreh A, et al.A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity[J].Pediatr Obes,2021,16(4): e12739.
[12] Hirschel J,Vogel M,Baber R, et al.Relation of whole blood amino acid and acylcarnitine metabolome to age, sex, BMI, puberty, and metabolic markers in children and adolescents[J].Metabolites,2020,10(4):149.
[13] Solon-Biet SM, Cogger VC, Pulpitel T, et al.Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control[J].Nat Metab,2019,1(5):532-545.
[14] Cosentino RG, Churilla JR, Josephson S, et al.Branched-chainamino acids and relationship with Inflammation in youth with obesity: A randomized controlled intervention study[J].J Clin Endocrinol Metab, 2021, 106(11): 3129-3139.
[15] Cifarelli V, Beeman SC, Smith GI, et al.Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity[J].J Clin Invest, 2020, 130(12): 6688-6699.
[16] Salinas-Rubio D, Tovar AR, Noriega LG.Emerging perspectives on branched-chain amino acid metabolism during adipocyte differentiation[J].Curr Opin Clin Nutr Metab Care, 2018, 21(1): 49-57.
[17] Rivera ME, Lyon ES, Johnson MA, et al.Leucine increases mitochondrial metabolism and lipid content without altering insulin signaling in myotubes[J].Biochimie, 2020,168:124-133.
[18] Becetti I, Lauze M, Lee H,et al.Changes in branched-chain amino acids one year after sleeve gastrectomy in youth with obesity and their association with changes in insulin resistance[J].Nutrients, 2023, 15(17): 3801
[19] De Bandt JP, Coumoul X, Barouki R.Branched-chain amino acids and insulin resistance, from protein supply to diet-induced obesity[J].Nutrients,2022,15(1):68.
[20] 董瀚文, 卢环宇, 张皓琪,等.支链氨基酸代谢与胰岛素抵抗的研究进展[J].中南医学科学杂志, 2023, 51(6): 970-973.
Dong HW, Lu HY, Zhang HQ, et al.Research progress on the metabolism of branched-chain amino acids and insulin resistance[J].Cent South Med Sci J, 2023,51(6): 970-973.(in Chinese)
[21] Orczyk-Pawilowicz M, Jawien E, Deja S, et al.Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy[J].PLoS One, 2017,11(4): e0152740.
[22] Manta-Vogli PD, Schulpis KH, Dotsikas Y, et al.The significant role of amino acids during pregnancy: Nutritional support[J].J Matern Fetal Neonatal Med,2020,33(2):334-340.
[23] James-Allan LB, Teal S, Powell TL, et al.Changes in placental nutrient transporter protein expression and activity across gestation in normal and obese women[J].Reprod Sci,2020, 27(9): 1758-1769.
[24] 吴红花.胰岛素抵抗与妊娠期糖尿病[J].中华糖尿病杂志, 2020, 12(7): 436-439.
Wu HH.Insulin resistance and gestational diabetes[J].Chin J Diabetes, 2020, 12(7): 436-439.(in Chinese)
[25] Holeček M.Why are branched-chain amino acids increased in starvation and diabetes?[J].Nutrients, 2020, 12(10): 3087.
[26] Zhao H, Wong RJ, Stevenson DK.The placental vasculature is affected by changes in gene expression and glycogen-rich cells in a diet-induced obesity mouse model[J].PLoS One,2023,18(11): e0294185.
[27] Borengasser SJ, Baker PR 2nd, Kerns ME, et al.Preconception micronutrient supplementation reduced circulating branched chain amino acids at 12 weeks gestation in an open trial of guatemalan women who are overweight or obese[J].Nutrients,2018, 10(9): e1282.
[28] Kivelä J, Sormunen-Harju H, Girchenko PV, et al.Longitudinal metabolic profiling of maternal obesity, gestational diabetes, and hypertensive pregnancy disorders[J].J Clin Endocrinol Metab,2021,106(11): e4372-e4388.
[29] Dai J, Boghossian NS, Sarzynski MA, et al.Metabolome-wide associations of gestational weight gain in pregnant women with overweight and obesity[J].Metabolites,2022,12(10):e960.
[30] Shearer J, Klein MS, Vogel HJ, et al.Maternal and cord blood metabolite associations with gestational weight gain and pregnancy health outcomes[J].J Proteome Res, 2021, 20(3): 1630-1638.
[31] Paul HA, Collins KH, Bomhof MR, et al.Potential impact of metabolic and gut microbial response to pregnancy and lactation in lean and diet-induced obese rats on offspring obesity risk[J].Mol Nutr Food Res, 2018, 62(4).doi:10.1002/mnfr.201700820.
[32] Anand NS, Ji Y, Wang G, et al.Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder:A prospective birth cohort study[J].J Child Psychol Psychiatry, 2021, 62(7): 868-875.
[33] Mokkala K, Vahlberg T, Pellonperä O, et al.Distinct metabolic profile in early pregnancy of overweight and obese women developing gestational diabetes[J].J Nutr, 2020, 150(1): 31-37.
[34] Shokry E, Marchioro L, Uhl O, et al.Impact of maternal BMI and gestational diabetes mellitus on maternal and cord blood metabolome: Results from the PREOBE cohort study[J].Acta Diabetol,2019,56(4): 421-430.
[35] Vanweert F, Schrauwen P, Phielix E.Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes[J].Nutr Diabetes,2022,12(1): 35.
[36] Gojda J, Cahova M.Gut microbiota as the link between elevated BCAA serum levels and insulin resistance[J].Biomolecules,2021, 11(10): 1414.
[37] Maitre L, Villanueva CM, Lewis MR, et al.Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study[J].BMC Med, 2016, 14(1): 177.
[38] Lowe WL Jr, Bain JR, Nodzenski M, et al.Maternal BMI andglycemia impact the fetal metabolome[J].Diabetes Care, 2017, 40(7): 902-910.
[39] Guixeres-Esteve T, Ponce-Zanón F, Morales JM, et al.Impact of maternal weight gain on the newborn metabolome[J].Metabolites, 2023, 13(4): 561.
[40] Manta-Vogli PD, Schulpis KH, Dotsikas Y, et al.The significant role of amino acids during pregnancy: nutritional support[J].J Matern Fetal Neonatal Med, 2020, 33(2): 334-340.
[41] Chang EI, Wesolowski SR, Gilje EA, et al.Skeletal muscle amino acid uptake is lower and alanine production is greater in late gestation intrauterine growth-restricted fetal sheep hindlimb[J].Am J Physiol Regul Integr Comp Physiol, 2019, 317(5): R615-R629.
[42] Ye Z, Wang S, Zhang C, et al.Coordinated modulation of energy metabolism and inflammation by branched-chain amino acids and fatty acids[J].Front Endocrinol (Lausanne), 2020, 11: 617.
[43] Tain YL, Hsu CN.Amino acids during pregnancy and offspring cardiovascular-kidney-metabolic health[J].Nutrients, 2024, 16(9): 1263.
[44] Fattuoni C, Mandò C, Palmas F, et al.Preliminary metabolomics analysis of placenta in maternal obesity[J].Placenta, 2018, 61:89-95.
[45] Marshall NE, Purnell JQ, Thornburg KL.Higher maternal essential amino acid levels are associated with higher placental amino acid transporter gene expression[J].Am J Obstet Gynecol, 2017, 216(Suppl 1): 317-318.
[46] Shao X, Cao G, Chen D, et al.Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply[J].Proc Natl Acad Sci U S A, 2021, 118(3): 1-11.
[47] Gupta MB, Jansson T.Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth[J].Biol Reprod, 2019, 100(4): 872-884.
[48] Jhanwar-Uniyal M, Wainwright VJ, Mohan LA, et al.Diverse signaling mechanisms of mTOR complexes: mTORC1 and mTORC2 in forming a formidable relationship[J].Adv Biol Regul, 2019, 77: 51-62.
[49] Chen J, Yue C, Xu J, et al.Downregulation of receptor tyrosine kinase-like orphan receptor 1 in preeclampsia placenta inhibits human trophoblast cell proliferation, migration, and invasion by PI3K/AKT/mTOR pathway accommodation[J].Placenta, 2019, 82: 17-24.
[50] Kelly AC, Powell TL, Jansson T.Placental function in maternal obesity[J].Clin Sci (Lond), 2020, 134(8): 961-984.
[51] Shimada H, Powell TL, Jansson T.Regulation of placental amino acid transport in health and disease[J].Acta Physiol (Oxf), 2024, 240(7): 14157.
[52] Dumolt JH, Powell TL, Jansson T.Placental function and the development of fetal overgrowth and fetal growth restriction[J].Obstet Gynecol Clin North Am, 2021, 48(2): 247-266.
[53] Rosario FJ, Urschitz J, Powell TL, et al.Overexpression of the LAT1 in primary human trophoblast cells increases the uptake of essential amino acids and activates mTOR signaling[J].Clin Sci (Lond), 2023, 137(21): 1651-1664.
[54] Ma QX, Zhu WY, Lu XC, et al.BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16[J].Nature metabolism,2022,4(1):106-122.
[55] Rosario FJ, Powell TL, Jansson T.Activation of placental insulin and mTOR signaling in a mouse model of maternal obesity associated with fetal overgrowth[J].Am J Physiol Regul Integr Comp Physiol, 2016, 310(1): R87-R93.
[56] Zhou M, Shao J, Wu CY, et al.Targeting BCAA catabolism to treat obesity-associated insulin resistance[J].Diabetes,2019,68(9):1730-1746.