The mediating role of syndecan-4 in the negative association of healthy eating index with body mass index and android percent fat in premenopausal women
Restricted accessResearch articleFirst published online January, 2026
The mediating role of syndecan-4 in the negative association of healthy eating index with body mass index and android percent fat in premenopausal women
Background: Diet quality has been implicated in the development of abdominal obesity. Yet, the molecular components involved in this relationship remain largely unknown. Aim: This pilot study examined whether syndecan-4 (SDC4) may serve as a molecular link between diet quality and abdominal obesity. Methods: Serum SDC4 levels were measured in 41 women (aged 21–45) who self-identified as African American or European American. Diet quality was assessed using the healthy eating index (HEI) score derived from a food frequency questionnaire, while android percent fat was measured using dual-energy X-ray absorptiometry. Regression and mediation analyses were performed to examine the data. Results: Significant (p < 0.05) negative correlations were observed between HEI scores and both body mass index (BMI) and android percent fat. SDC4 emerged as a significant predictor of HEI and mediated the negative associations of HEI with BMI and android percent fat, independent of race and age. Conclusion: Our findings suggest that SDC4 may play a key mechanistic role in linking adherence to dietary recommendations with reductions in android adiposity.
AsghariGMirmiranPYuzbashianE, et al. (2017) A systematic review of diet quality indices in relation to obesity. British Journal of Nutrition117(8): 1055–1065.
2.
AuneDGiovannucciEBoffettaP, et al. (2017) Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality—A systematic review and dose–response meta-analysis of prospective studies. International Journal of Epidemiology46(3): 1029–1056.
3.
BenoitSCCleggDJSeeleyRJ, et al. (2004) Insulin and leptin as adiposity signals. Recent Progress in Hormone Research59: 267–285.
4.
CedilloYEKnightRODarnellB, et al. (2022) Body fat percentage assessment using skinfold thickness agrees with measures obtained by DXA scan in African American and Caucasian American women. Nutrition Research105: 154–162.
5.
CroccoPVecchieDGopalkrishnaS, et al. (2023) Syndecan-4 as a genetic determinant of the metabolic syndrome. Diabetology & Metabolic Syndrome15(1): 156.
6.
De LucaMVecchieDAthmanathanB, et al. (2019) Genetic deletion of syndecan-4 alters body composition, metabolic phenotypes, and the function of metabolic tissues in female mice fed: A high-fat diet. Nutrients11(11): 2810.
7.
EspositoKKastoriniCMPanagiotakosDB, et al. (2011) Mediterranean diet and weight loss: Meta-analysis of randomized controlled trials. Metabolic Syndrome and Related Disorders9(1): 1–12.
8.
EspositoKMaiorinoMIBellastellaG, et al. (2015) A journey into a Mediterranean diet and type 2 diabetes: A systematic review with meta-analyses. BMJ Open5(8): e008222.
9.
FungTTMcCulloughMvan DamRM, et al. (2007) A prospective study of overall diet quality and risk of type 2 diabetes in women. Diabetes Care30(7): 1753–1757.
10.
GuhDPZhangWBansbackN, et al. (2009) The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health9: 88.
11.
GuoXWardenBAPaeratakulS, et al. (2004) Healthy eating index and obesity. European Journal of Clinical Nutrition58(12): 1580–1586.
12.
HenneinRLiuCMcKeownNM, et al. (2019) Increased diet quality is associated with long-term reduction of abdominal and pericardial fat. Obesity27(4): 670–677.
13.
KarvettiRLKnutsLR (1985) Validity of the 24-h dietary recall. Journal of the American Dietetic Association85(11): 1437–1442.
14.
KnightROCedilloYEJuddSE, et al. (2024) A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of Black and White women in Birmingham, Alabama. BMC Women's Health24(1): 142.
15.
KristalARKolarASFisherJL, et al. (2014) Evaluation of web-based, self-administered, graphical food frequency questionnaire. Journal of the Academy of Nutrition and Dietetics114(4): 613–621.
16.
KunnasTNikkariST (2014) Contribution of syndecan-4 genetic variants to hypertension, the TAMRISK study. BMC Research Notes7: 815.
17.
LandryRRiouxVBensadounA (2001) Characterization of syndecan-4 expression in 3T3-F442A mouse adipocytes: Link between syndecan-4 induction and cell proliferation. Cell Growth & Differentiation12(10): 497–504.
18.
LiMGongWWangS, et al. (2022) Trends in body mass index, overweight and obesity among adults in the USA, the NHANES from 2003 to 2018: A repeat cross-sectional survey. BMJ Open12(12): e065425.
19.
Manon-JensenTItohYCouchmanJR (2010) Proteoglycans in health and disease: The multiple roles of syndecan shedding. The FEBS Journal277(19): 3876–3889.
20.
Manon-JensenTMulthauptHACouchmanJR (2013) Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. The FEBS Journal280(10): 2320–2331.
21.
MinihaneAMVinoySRussellWR, et al. (2015) Low-grade inflammation, diet composition and health: Current research evidence and its translation. British Journal of Nutrition114(7): 999–1012.
22.
ReizesOGoldbergerOSmithAC, et al. (2006) Insulin promotes shedding of syndecan ectodomains from 3T3-L1 adipocytes: A proposed mechanism for stabilization of extracellular lipoprotein lipase. Biochemistry45(18): 5703–5711.
23.
RosatoVTempleNJLa VecchiaC, et al. (2019) Mediterranean diet and cardiovascular disease: A systematic review and meta-analysis of observational studies. European Journal of Nutrition58(1): 173–191.
24.
Shams-WhiteMMPannucciTELermanJL, et al. (2023) Healthy eating index-2020: Review and update process to reflect the dietary guidelines for Americans, 2020–2025. Journal of the Academy of Nutrition and Dietetics123(9): 1280–1288.
25.
StoleTPLundeMShenX, et al. (2022) The female syndecan-4(-/-) heart has smaller cardiomyocytes, augmented insulin/pSer473-Akt/pSer9-GSK-3beta signaling, and lowered SCOP, pThr308-Akt/Akt and GLUT4 levels. Frontiers in Cell and Developmental Biology10: 908126.
26.
SunKSchererLXEP (2023) Extracellular matrix (ECM) and fibrosis in adipose tissue: Overview and perspectives. Comprehensive Physiology13(1): 4387–4407.
27.
TakahashiIYamadaSNataK (2018) Effects of heparan sulfate proteoglycan syndecan-4 on the insulin secretory response in a mouse pancreatic beta-cell line, MIN6. Molecular and Cellular Endocrinology470: 142–150.
28.
TkachenkoERhodesJMSimonsM (2005) Syndecans: New kids on the signaling block. Circulation Research96(5): 488–500.
29.
TsuzakiJMaskarinecGMapaV, et al. (2023) Diet quality and body mass index over 20 years in the multiethnic cohort. Journal of the Academy of Nutrition and Dietetics124: 194–204.
30.
VahidFJaliliMRahmaniW, et al. (2022) A higher healthy eating index is associated with decreased markers of inflammation and lower odds for being overweight/obese based on a case-control study. Nutrients14(23): 5127.
31.
VasanSKOsmondCCanoyD, et al. (2018) Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk. International Journal of Obesity42(4): 850–857.
32.
WuHZhouQXieJ, et al. (2015) Syndecan-4 shedding is involved in the oxidative stress and inflammatory responses in left atrial tissue with valvular atrial fibrillation. International Journal of Clinical and Experimental Pathology8(6): 6387–6396.
33.
XuFEarpJEAdamiA, et al. (2022a) The relationship of physical activity and dietary quality and diabetes prevalence in US adults: Findings from NHANES 2011–2018. Nutrients14(16): 3324.
34.
XuFEarpJELoBuonoDL, et al. (2022b) The relationship of physical activity and dietary quality with android fat composition and distribution in US adults.Nutrients14(14): 2804.
