Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model

0571371 - FGÚ 2024 RIV CH eng J - Journal Article
Hüttl, M. - Marková, I. - Miklánková, D. - Zapletalová, I. - Kujal, P. - Šilhavý, Jan - Pravenec, Michal - Malínská, H.
Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model.
Frontiers in Pharmacology. Roč. 14, 3 Apr (2023), č. článku 1117683. ISSN 1663-9812. E-ISSN 1663-9812
R&D Projects: GA MŠMT(CZ) LX22NPO5104
Institutional support: RVO:67985823
Keywords : salsalate * low-grade inflammation * prediabetes * lipid metabolism * cytochrome P450 * oxidative stress
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 5.6, year: 2022
Method of publishing: Open access
https://doi.org/10.3389/fphar.2023.1117683

Results: Salsalate treatment of HHTg rats when compared to their untreated controls was associated with significant amelioration of inflammation, dyslipidemia and insulin resistance. Specificaly, salsalate treatment was associated with reduced inflammation, oxidative and dicarbonyl stress when inflammatory markers, lipoperoxidation products and methylglyoxal levels were significantly decreased in serum and tissues. In addition, salsalate ameliorated glycaemia and reduced serum lipid concentrations. Insulin sensitivity in visceral adipose tissue and skeletal muscle was significantly increased after salsalate administration. Further, salsalate markedly reduced hepatic lipid accumulation (triglycerides −29% and cholesterol −14%). Hypolipidemic effects of salsalate were associated with differential expression of genes coding for enzymes and transcription factors involved in lipid synthesis (Fas, Hmgcr), oxidation (Pparα) and transport (Ldlr, Abc transporters), as well as changes in gene expression of cytochrome P450 proteins, in particular decreased Cyp7a and increased Cyp4a isoforms.
Conclusion:These results demonstrate important anti-inflammatory and anti-oxidative effects of salsalate that were associated with reduced dyslipidemia and insulin resistance in HHTg rats. Hypolipidemic effects of salsalate were associated with differential expression of genes regulating lipid metabolism in the liver. These results suggest potential beneficial use of salsalate in prediabetic patients with NAFLD symptoms.

Permanent Link: https://hdl.handle.net/11104/0342610