Regulation of metabolic pathways genes and the effects of very low-calorie diet on insulin resistance and fatty acid profiles in obese patients undergoing bariatric surgery.

OBJECTIVES

To evaluate the effects of a very-low-calorie diet (VLCD) on insulin resistance (IR), metabolic gene expression, and fatty acid profiles in obese patients (body mass index [BMI] ≥ 30 kg/m) undergoing bariatric surgery compared to age- and sex-matched nonobese controls (BMI ≤ 25 kg/m) undergoing elective abdominal surgery.

METHODS

A total of 38 participants (21 obese and 17 nonobese controls) were recruited for this study. Obese patients underwent VLCD (800 kcal/day) for four weeks before surgery. Fasting blood samples and tissue biopsies were collected during surgery. Key parameters included IR (measured using HOMA-IR), metabolic gene expression (quantified via RT-PCR), and fatty acid composition (analyzed by gas chromatography). Data were compared between pre- and post-VLCD groups in the obese cohort.

RESULTS

GLUT4 expression was reduced (1.57-fold,  = 0.025), whereas PDK4 (3.9-fold,  = 0.002), CPT1 (2.5-fold,  = 0.013), and AMPK (twofold,  = 0.004) expression were Correlation analysis revealed that GLUT4 was negatively correlated with BMI (r = -0.85), glucose (r = -0.94), and IR (r = -0.79), CPT1 was positively correlated with these parameters (BMI: r = 0.84, glucose: r = 0.92, IR: r = 0.82). VLCD significantly reduced monounsaturated fatty acids, including alpha-linolenic acid ( = 0.03) and erucic acid ( = 0.019). Postsurgical improvements included reductions in BMI (Δ = 6.21,  < 0.0001), glucose level (Δ = 6.94,  = 0.0007), and IR (Δ = 10.19,  = 0.0039).

CONCLUSION

VLCD modulated metabolic gene expression and fatty acid profiles, enhancing IR and metabolic health both pre- and post-surgery. This represents a critical strategy for optimizing the outcomes of obese patients undergoing bariatric surgery.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s40200-025-01625-5.