Polymorphisms Involved in Insulin Resistance and Metabolic Inflammation: Influence of Nutrients and Dietary Interventions
Abstract
:1. Introduction
2. Materials and Methods
3. Results and Discussion
3.1. IR and Metabolic Inflammation
3.2. Gene–Nutrient Interactions in IR: Evidence of Functional Consequences of Genetic Polymorphism
3.2.1. TCF7L2
3.2.2. SLC30A8 (ZnT8)
3.2.3. IRS-1
3.2.4. TNF-α
3.2.5. TLR-4
3.2.6. IL-6
3.2.7. PPAR-γ
3.2.8. Adiponectin
3.3. Effects of Nutritional Interventions on Polygenic Risk Scores Affecting IR Biomarkers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ADIPOQ: | Adiponectin |
APOA-1: | Apolipoprotein A-1 |
BMI: | Body Mass Index |
DASH: | Dietary Approaches to Stop Hypertension |
DNL: | De Novo Lipogenesis |
FTO: | Fat Mass and Obesity Associated |
GWAS: | Genome-Wide Association Studies |
HbA1c: | Glycated Hemoglobin |
HDL: | High-Density Lipoprotein |
HOMA-IR: | Homeostasis Model Assessment of Insulin Resistance |
IL-6: | Interleukin-6 |
IRS: | Insulin Receptor Substrate |
IR: | Insulin Resistance |
JNK: | c-Jun N-terminal Kinase |
MedDiet: | Mediterranean Diet |
MC4R: | Melanocortin-4 Receptor |
MUFA: | Monounsaturated Fatty Acids |
NF-κB: | Nuclear Factor Kappa B |
PUFA: | Polyunsaturated Fatty Acids |
PRS: | Polygenic Risk Score |
SNP: | Single-Nucleotide Polymorphism |
SAFA: | Saturated Fatty Acids |
TCF7L2: | Transcription Factor 7-Like 2 |
TLR: | Toll-Like Receptor |
TNF-α: | Tumor Necrosis Factor-Alpha |
T2DM: | Type 2 Diabetes |
TyG: | Triglyceride-Glucose Index |
GRS: | Genetic Risk Score |
PRS: | Polygenic Risk Score |
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Gene | SNPs | Nutrients and/or Nutritional Intervention | Main Findings |
---|---|---|---|
TCF7L2 | rs7903146 (C > T) and rs12255372 (G > T) | Mediterranean Diet | (1) T allele for both SNPs: individuals with high adherence to the Mediterranean diet presented ↓ weight, BMI, WC [56], and lower risk for GDM [57]; (2) individuals with low adherence had higher fasting glucose [55]. |
rs7903146 (C > T) | Quantitative evaluation of dairy products (>200 mL/day), processed sweets (>30 g/day), and refined grains (≥5 portions/week) | T allele: individuals with higher consumption of desserts and milk had ↑ risk for T2D [52]. | |
Evaluation of habitual intake of SAFA (low intake ≤ 12% TEV and high intake ≥ 15%TEV) | T allele: ↑ intake of SAFA associated with impaired insulin sensitivity [53]. | ||
Evaluation of intake of whole grains (>50 g/day vs. <30 g/day) | GG genotype: 14% less risk of developing T2D [54]. | ||
DASH diet or legume-based DASH diet | No effects of the SNP on inflammatory biomarkers or oxidative stress indicator [58]. | ||
SLC30A8 rs13266634 (C > T) | Zinc intake | TT genotype: zinc supplement users had a more pronounced reduction in T2D risk [65]. | |
Supplementation of oral zinc acetate | (1) CT/TT genotypes: ↑ fasting insulin. (2) No differences between genotypes for serum zinc concentration [66]. | ||
MMTT test with high lipids content (60% lipids; 25% carbohydrates; 15% proteins) | (1) CC genotype: ↓ NEFA in men. (2) TT genotype carriers: ↑ insulin basal levels in women and attenuated lipid response with no gender-specific effect [67]. | ||
IRS1 | rs2943641 (T > A) | Macronutrients intake | T allele: ↓ T2D risk in lower tertiles of carbohydrate intake for women and in the lower tertiles of fat intake for men [71]. |
rs2943634 (A > C) | Counseling program: reduction in refined carbohydrates (<45% TEV), emphasis on dietary fiber (>25 g/day) | A allele: associated with ↓ carbohydrate intake [72]. | |
rs2943641 (T > A) and rs7578326 (A > G) | Dietary analysis of SAFA: carbohydrates (Group 1: Ratio ≤0.24 and Group 2: Ratio >0.24) and MUFA intake | (1) haplotype G-T: ↓ risk of IR and MetS with low dietary SAFA-to-carbohydrate ratio. (2) G allele: ↓ MetS risk when dietary MUFA was lower than median intake [27]. | |
TNF | rs7903146 (C > T) | Mediterranean Diet | GG genotype: improvement of TG and plasma hsCRP after 1 year of intervention [77]. |
Fatty acids intake evaluation | A allele: ↑ inflammation— ↑ plasma stearic acid and SAFA [74]. | ||
TLR4 | rs4986790 (Asp299Gly) and rs5030718 (G > A) | Dietary fat intake evaluation | (1) Gly allele: ↑ insulin, HOMA-IR, and HOMA-β. (2) G allele: SFA intake -> inversely associated with HDL-c among GG individuals and a positive relationship for GA [85] |
IL6 | rs1800795 (G > C) | 3 intervention groups: (a) lower fat and higher carbohydrate; (b) lower carbohydrate and higher fat; or (c) a walnut-rich diet, with higher fat and lower carbohydrate. | CC genotype: ↓ IL-6 levels before adjustment for BMI [92]. |
PPARG | rs1801282 (C > G | Mediterranean Diet or Centro-European diet | (1) Central European diet—G allele: ↓ weight, lean mass, and HDL-c. (2) Mediterranean Diet—G allele: ↓ abdominal fat [96]. |
2-year behavioral weight-loss program based on Mediterranean Diet | (1) CG/GG genotype: baseline—↓ insulin and HOMA-IR; (2) G allele: after intervention—↑ % of weight loss and body fat, especially in those with high MUFA intake [97]. | ||
High SAFA content or high PUFA intake | (1) CC genotype: a positive association between total fat intake and WC [98]; (2) PUFA diet—↑ HDL-c and APOA [99]. | ||
3 interventional groups: extra virgin olive oil supplementation (50 mL/day), a traditional Brazilian diet (TBD), or a TBD with extra virgin olive oil supplementation. | TBD with extra virgin olive oil supplementation: weight loss and improvement body composition independently of genotype [100]. | ||
↓ body weight, fasting glucose, and HOMA-IR independent of genotype [101]. | |||
Daily DHA-rich fish oil supplementation | |||
ADIPOQ | rs1501299 (G > T) | Carbohydrate intake evaluation | T allele carriers influence the degree to which fasting glucose, HbA1C e HDL-c are affected by the amount of carbohydrate intake [108]. |
rs2241766 (G > A) | High-monounsaturated diet | A allele: ↓ serum adiponectin [110]. |
PRS/GRS Composition | Nutrients and/or Nutritional Intervention | Nutrients and/or Nutritional Intervention |
---|---|---|
10 SNPs associated with glucose and insulin metabolism, and obesity (rs12255372, rs7903146, rs17782313, rs8050136, rs10163409, rs2237892, rs2237895, rs10811661, rs5030952, rs1801282) | Macronutrients intake | Individuals within the high-fat intake category and with ≥5 risk alleles: ↑ fasting insulin, insulin-glucose ratio, HOMA-β, and HOMA-IR than those with < 5 risk allele [113]. |
16 SNPs associated with metabolic traits (rs3792267, rs5030952, rs9939609, rs10163409, rs8050136, rs17782313, rs2229616, rs12255372, rs7903146, rs2237895, rs2237892, rs10811661, rs1801282, s266729, rs17846866) | Protein intake evaluation | No influence of PRS on dietary protein intake and glucose concentration, insulin, and HbA1C [114]. |
23 SNPs associated with metabolic traits (rs1801133, rs7903146, rs12255372, rs8050136, rs9939609, rs17782313, rs1801282, rs5219, rs2237895, rs2237892, rs10741567, rs12794714, rs12785878, rs6013897, rs2282679, rs6680429, rs266729, rs10811661, rs1801725, rs5030952, rs3742801, rs2270655, rs778805) | MUFA intake evaluation | Women with ↓ MUFA intake (<7.0 g/day) and a higher PRS (>13 risk allele) had elevated HbA1C [115] |
8 SNPs associated with changes in the HOMA-IR after n-3 PUFA supplementation (rs72723587, rs77850702, rs72703546, rs17174795, rs12437986, rs35621498, rs55842940, rs6001872) | Omega-3 PUFA supplementation (5 g/day of fish oil) | ↑ PRS increased HOMA-IR after dietary intervention [116] |
21 SNPS associated with obesity (rs2010899, rs4135275, rs4912905, rs9355296, rs1524107, rs2183013, rs1019731, rs1568400, rs4246444, rs7701443, rs13182800, rs3211867, rs2515362, rs1800497, rs9939609, rs4783961, rs8068149, rs7502966, rs1044250, rs17373080, rs2143511). | Mediterranean Diet | Women with adherence to the intervention diet and ↑ PRS: improvement of IR [117] |
5 SNPs associated with T2D risk (rs2237892, rs2206734, rs2383208, rs6780569, rs1470579) | Intake of 150 g of yogurt | ↑ PRS group: improvement of postprandial plasma glucose, insulin, and HOMA-IR after the intervention [118] |
16 SNPs associated with T2D (rs3923113, rs1801282, rs11717195, rs4402960, rs6878122, rs7756992, rs849135, rs516946, rs17791513, rs2796441, rs11257655, rs7903146, rs10830963, rs7403531, rs7202877, rs5945326, rs188827514) | Sugar-sweetened beverages (SSB) intake evaluation | SSB intake: increased glucose levels in individuals with ↑ PRS [119] |
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Duarte, G.B.S.; Pascoal, G.d.F.L.; Rogero, M.M. Polymorphisms Involved in Insulin Resistance and Metabolic Inflammation: Influence of Nutrients and Dietary Interventions. Metabolites 2025, 15, 245. https://doi.org/10.3390/metabo15040245
Duarte GBS, Pascoal GdFL, Rogero MM. Polymorphisms Involved in Insulin Resistance and Metabolic Inflammation: Influence of Nutrients and Dietary Interventions. Metabolites. 2025; 15(4):245. https://doi.org/10.3390/metabo15040245
Chicago/Turabian StyleDuarte, Graziela Biude Silva, Gabriela de Freitas Laiber Pascoal, and Marcelo Macedo Rogero. 2025. "Polymorphisms Involved in Insulin Resistance and Metabolic Inflammation: Influence of Nutrients and Dietary Interventions" Metabolites 15, no. 4: 245. https://doi.org/10.3390/metabo15040245
APA StyleDuarte, G. B. S., Pascoal, G. d. F. L., & Rogero, M. M. (2025). Polymorphisms Involved in Insulin Resistance and Metabolic Inflammation: Influence of Nutrients and Dietary Interventions. Metabolites, 15(4), 245. https://doi.org/10.3390/metabo15040245