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Background <p>Common variants in the fat mass and obesity–associated (FTO) gene are linked to obesity and cardiometabolic risk, but whether they modify lipid and glycemic responses to continuous energy restriction (CER) remains unclear. We evaluated genotype-specific changes in lipid and glycemic biomarkers following CER-based dietary interventions in adults with overweight/obesity.</p> Methods <p>A literature search of four databases identified eligible intervention trials published through March 2026. Results were synthesized using random-effects meta-analyses, reporting mean differences (MDs) with 95% confidence intervals (CI). Subgroup analyses and sensitivity analyses were conducted, and the certainty of evidence was assessed.</p> Results <p>Fifteen articles (18 effect sizes for lipid outcomes; 21 for glycemic outcomes; 4,941 participants). Compared with non-carriers, FTO risk-allele carriers had higher triglycerides (MD 5.98&#xa0;mg/dL; 95% CI 1.03 to 10.93). No significant genotype-related differences were observed for total cholesterol, LDL-C, HDL-C, fasting glucose, insulin, or HOMA-IR, and all sensitivity analyses were consistent with these findings. Subgroup tests showed no significant differences by intervention duration, study design or genotype model. Genotype-contrast analyses suggested differences in triglycerides and LDL-C (higher TG in AA carriers and greater LDL-C reduction in AA carriers) and in fasting glucose (greater reduction in AT/AA carriers) compared with non-carriers. Overall certainty of evidence ranged from low to very low (GRADE).</p> Conclusions <p>Most lipid and glycemic markers were comparable across FTO genotypes during CER, whereas triglycerides were higher in risk-allele carriers. Replication in prospective trials with pre-specified genetic stratification is needed before these findings can inform clinical practice.</p>

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Response of FTO gene polymorphisms to continuous caloric restriction diets on lipid and glycemic biomarkers in overweight and obese adults: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Tran Quang Duc,
  • Nguyen Di Khanh,
  • Dang Dang Khoa,
  • Nguyen Huynh Phuong Anh

摘要

Background

Common variants in the fat mass and obesity–associated (FTO) gene are linked to obesity and cardiometabolic risk, but whether they modify lipid and glycemic responses to continuous energy restriction (CER) remains unclear. We evaluated genotype-specific changes in lipid and glycemic biomarkers following CER-based dietary interventions in adults with overweight/obesity.

Methods

A literature search of four databases identified eligible intervention trials published through March 2026. Results were synthesized using random-effects meta-analyses, reporting mean differences (MDs) with 95% confidence intervals (CI). Subgroup analyses and sensitivity analyses were conducted, and the certainty of evidence was assessed.

Results

Fifteen articles (18 effect sizes for lipid outcomes; 21 for glycemic outcomes; 4,941 participants). Compared with non-carriers, FTO risk-allele carriers had higher triglycerides (MD 5.98 mg/dL; 95% CI 1.03 to 10.93). No significant genotype-related differences were observed for total cholesterol, LDL-C, HDL-C, fasting glucose, insulin, or HOMA-IR, and all sensitivity analyses were consistent with these findings. Subgroup tests showed no significant differences by intervention duration, study design or genotype model. Genotype-contrast analyses suggested differences in triglycerides and LDL-C (higher TG in AA carriers and greater LDL-C reduction in AA carriers) and in fasting glucose (greater reduction in AT/AA carriers) compared with non-carriers. Overall certainty of evidence ranged from low to very low (GRADE).

Conclusions

Most lipid and glycemic markers were comparable across FTO genotypes during CER, whereas triglycerides were higher in risk-allele carriers. Replication in prospective trials with pre-specified genetic stratification is needed before these findings can inform clinical practice.