# Effects of High-Monounsaturated-Fatty-Acid (MUFA) Diet and Melatonin Supplementation on Lipid Metabolism in Female Rats

**Authors:** Jun-Ling Luo, Yi-Wen Chien

PMC · DOI: 10.3390/biology15060515 · Biology · 2026-03-23

## TL;DR

This study found that melatonin and a high-MUFA diet altered gene expression related to lipid metabolism in female rats, but without clear health benefits.

## Contribution

The study reveals distinct molecular responses to melatonin and high-MUFA diets in lipid metabolism without physiological improvements.

## Key findings

- Melatonin and high-MUFA diet upregulated genes like PPARα and ACO in the liver.
- High-MUFA diet increased HSL expression in adipose tissue.
- Combined treatment altered FNDC5 and PGC-1α expression without affecting serum irisin.

## Abstract

This study explored whether melatonin supplementation and a high-monounsaturated-fatty-acid (MUFA) diet were associated with changes in lipid metabolism-related gene expression in female rats. After eight weeks, no significant changes were observed in body weight or blood lipid profiles. However, the combination of melatonin and the high-MUFA diet enhanced the expression of hepatic genes involved in fat oxidation, including peroxisome proliferator-activated receptor α (PPARα) and acyl-CoA oxidase (ACO), and the high-MUFA diet increased hormone-sensitive lipase (HSL) expression in adipose tissue. Interestingly, this combined treatment also upregulated fibronectin type III domain-containing protein 5 (FNDC5) while downregulating peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). These findings indicate that melatonin and dietary fatty acid composition are associated with distinct molecular responses related to lipid metabolism; however, these responses did not translate into clear physiological benefits, highlighting the need for longer-term studies to clarify their biological significance.

Background: This study investigated the effects of melatonin (50 mg/kg/day) and a high-monounsaturated-fatty-acid (MUFA) diet (60% MUFAs; PUFA/SFA ratio = 5), alone or combined, on lipid metabolism-related gene expression in female Sprague–Dawley rats. Methods: Thirty-two eight-week-old rats were randomized into four groups: control (C), melatonin (M), experimental oil diet (E), and combined melatonin plus experimental oil diet (ME). Treatments lasted eight weeks, with melatonin given orally at 17:00–19:00 daily. Results: In the ME group, hepatic expression of peroxisome proliferator-activated receptor α (PPARα) and acyl-CoA oxidase (ACO) mRNA was markedly upregulated, while the E group showed significantly higher expression of hormone-sensitive lipase (HSL) in white adipose tissue. Additionally, ME rats exhibited increased fibronectin type III domain-containing protein 5 (FNDC5) mRNA with reduced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), but serum irisin remained unchanged. Conclusions: Melatonin and a high-MUFA diet induced modest and non-uniform changes in lipid metabolism-related gene expression. However, these transcriptional responses were not accompanied by measurable physiological or metabolic outcomes, indicating that the observed effects represent early molecular adaptations rather than functional metabolic modulation.

## Linked entities

- **Genes:** PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465], KLK15 (kallikrein related peptidase 15) [NCBI Gene 55554], LIPE (lipase E, hormone sensitive type) [NCBI Gene 3991], FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891]
- **Chemicals:** melatonin (PubChem CID 896)

## Full-text entities

- **Genes:** Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 25747] {aka PPAR}, Actb (actin, beta) [NCBI Gene 81822] {aka Actx}, Ucp1 (uncoupling protein 1) [NCBI Gene 24860] {aka Ucp, Ucpa, Uncp}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 78968] {aka ADD-1, ADD1, SREBP-1, SREBP-1c, Srebp1}, Lep (leptin) [NCBI Gene 25608] {aka OB, obese}, Fasn (fatty acid synthase) [NCBI Gene 50671], Cpt1b (carnitine palmitoyltransferase 1B) [NCBI Gene 25756] {aka CPT-IB, M-CPTI}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Pparg (peroxisome proliferator-activated receptor gamma) [NCBI Gene 25664] {aka PPARgamma2}, Adipoq (adiponectin, C1Q and collagen domain containing) [NCBI Gene 246253] {aka Acdc, Acrp30, Adid}, Fndc5 (fibronectin type III domain containing 5) [NCBI Gene 260327], Lipe (lipase E, hormone sensitive type) [NCBI Gene 25330] {aka HSL, REH}, Lpl (lipoprotein lipase) [NCBI Gene 24539], Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}
- **Diseases:** injury to (MESH:D014947), insulin resistance (MESH:D007333), dyslipidemia (MESH:D050171), obese (MESH:D009765), cardiovascular disease (MESH:D002318), hepatic necrosis (MESH:D047508), metabolic dysfunction (MESH:D008659), necrosis (MESH:D009336), postmenopausal metabolic syndrome (MESH:D024821), hypertrophy (MESH:D006984), adiposity (MESH:D018205), chronic inflammation (MESH:D007249), steatosis (MESH:D005234)
- **Chemicals:** High-Monounsaturated-Fatty-Acid (-), cholesterol (MESH:D002784), -Monounsaturated-Fatty-Acid (MESH:D005229), Zoletil (MESH:C006131), cAMP (MESH:D000242), FA (MESH:D005227), ethanol (MESH:D000431), malonyl-CoA (MESH:D008316), eosin (MESH:D004801), fat (MESH:D005223), Lipid (MESH:D008055), TG (MESH:D014280), glycerol (MESH:D005990), Trizol (MESH:C411644), paraffin (MESH:D010232), Estradiol (MESH:D004958), Rompun (MESH:D014991), PUFA (MESH:D005231), formalin (MESH:D005557), oil (MESH:D009821), canola oil (MESH:D000074262), H&amp;E (MESH:D006371), hematoxylin (MESH:D006416), S (MESH:D013455), glucose (MESH:D005947), Melatonin (MESH:D008550), FFA (MESH:D005230), P (MESH:D010758)
- **Species:** Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Cricetinae (hamsters, subfamily) [taxon 10026]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13023522/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC13023522/full.md

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Source: https://tomesphere.com/paper/PMC13023522