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

**Authors:** Mohammad Mehrtash, Mohsen Salesi, Farhad Daryanoosh, Nader Tanideh, Iman Jamhiri

PMC · DOI: 10.1155/omcl/6888340 · Oxidative Medicine and Cellular Longevity · 2026-02-06

## TL;DR

Combining calorie restriction and resistance training significantly improves weight loss and insulin sensitivity in rats with diet-induced obesity.

## Contribution

The study reveals that combining caloric restriction and resistance training synergistically regulates lipid droplet proteins and metabolic pathways.

## Key findings

- CR+RT reduced body weight by 42.7g compared to the HFD group.
- CR+RT improved insulin sensitivity to levels comparable to normal diet controls.
- CR+RT upregulated ATGL, AMPK, SIRT1, and PGC-1α while downregulating perilipin 1 and FSP-27 in skeletal muscle.

## Abstract

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).

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‐1α), sirtuin 1 (SIRT1), and AMP‐activated protein kinase (AMPK) were measured only in skeletal muscle after the subsequent 8‐week intervention period.

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‐1α compared to HFD (all p  < 0.05).

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.

## Linked entities

- **Genes:** SIRT1 (sirtuin 1) [NCBI Gene 489012]
- **Proteins:** CIDEC (cell death inducing DFFA like effector c), PNPLA2 (patatin like domain 2, triacylglycerol lipase), PPARGC1A (PPARG coactivator 1 alpha), SIRT1 (sirtuin 1), PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** Plin1 (perilipin 1) [NCBI Gene 25629] {aka PERIA, Plin}, Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, Plin5 (perilipin 5) [NCBI Gene 501283] {aka Oxpat}, Pnpla2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 361676] {aka RGD1309044}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}
- **Diseases:** Obesity (MESH:D009765), Insulin resistance (MESH:D007333)
- **Chemicals:** lipid (MESH:D008055), fat (MESH:D005223)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12880951/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12880951/full.md

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Source: https://tomesphere.com/paper/PMC12880951