Impact of Caloric Restriction and Resistance Training on Weight Management, Insulin Sensitivity, and Adipose Tissue Protein Dynamics

Background/Aims Obesity and insulin resistance induced by excessive calorie intake remain major health challenges. Caloric restriction (CR) and resistance training (RT) are known strategies to improve metabolic health, but their combined effects on lipid droplet‐associated proteins and metabolic regulators remain unclear. This study aimed to evaluate the impact of CR and RT, alone and in combination (CR + RT), on lipid droplet‐associated proteins and signaling pathways in rats exposed to a high‐fat diet (HFD). Methods Fifty male Sprague–Dawley rats were fed HFD for 8 weeks and were then randomly assigned to five groups: HFD, normal‐fat diet (NFD), CR, RT, and CR + RT. Each intervention was performed for 8 weeks following the initial 8‐week HFD induction. Body weight, insulin resistance index (HOMA‐IR), and mRNA expression of perilipin 1 was measured in both adipose and skeletal muscle tissues, whereas perilipin 5, fat‐specific protein 27 (FSP‐27), adipose triglyceride lipase (ATGL), peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1 α ), sirtuin 1 (SIRT1), and AMP‐activated protein kinase (AMPK) were measured only in skeletal muscle after the subsequent 8‐week intervention period. Results At baseline, no significant differences in body weight were observed among the groups ( p > 0.05). After 16 weeks, rats in HFD group exhibited the highest body weight (509.8 ± 6.0g), whereas CR + RT group showed the most pronounced reduction (292.2 ± 1.8 g; p < 0.001). Insulin resistance (HOMA‐IR) was significantly elevated in the HFD group (5.55 ± 0.21) compared to all other groups, while the CR + RT group demonstrated the lowest value (1.24 ± 0.05), comparable to the normal diet group ( p > 0.05). At the molecular level, CR + RT downregulated perilipin 1 and FSP‐27, while significantly upregulating ATGL, AMPK, SIRT1, and PGC‐1 α compared to HFD (all p < 0.05). Conclusion Combined CR and RT produced superior benefits over either intervention alone, improving insulin sensitivity and lipid metabolism through coordinated regulation of lipid droplet proteins and metabolic signaling pathways. These findings suggest CR+RT as an effective strategy against diet‐induced obesity.