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Effect of spexin on renal dysfunction in experimentally obese rats: potential mitigating mechanisms via galanin
Mervat H El-Saka1, Rehab E Abo El Gheit1, Amira El Saadany2
1Department of Physiology, Tanta University, Tanta, Egypt.
Abstract:
This study declared effect of spexin (SPX) on renal dysfunction in obese rats and its potential mitigating mechanisms which could mediated via galanin receptor-2 (GALR-2). Thirty two 32 Wistar male rats were arranged into four groups: control, high fat/fructose diet (HFFD), HFFD + SPX and HFFD + M871 (galanin receptor 2 antagonist)+SPX. At the termination of the experiment, urine volume, body mass index, Lee index and mean arterial blood pressure were assessed. Renal function was evaluated. Lipid profile, fasting glucose, insulin, insulin resistance and SPX levels were estimated. Also, renal histopathological, immunohistochemical and relative gene expression of renal tissue were done. Also, renal protein carbonyl, reduced glutathione, interferon gamma, monocyte chemoattractant protein-1, interleukin-10 and hydroxyproline were determined.Our results explored that SPX treatment prominently mitigated the metabolic changes and renal dysfunction induced by HFFD via GALR-2. SPX improved insulin resistance, dyslipidemia, renal oxidative stress, inflammation, apoptosis, and fibrosis. So, SPX can be considered as prospective therapeutic agent for treating renal dysfunction.
Insights
Spexin (SPX) significantly improved kidney function in obese rats by reducing metabolic changes and inflammation. This therapeutic effect was mediated through the galanin receptor-2 (GALR-2) pathway.
Area of Science:
- Metabolic research
- Renal physiology
- Pharmacology
Background:
- Obesity induced by high-fat/fructose diets (HFFD) leads to metabolic disturbances and renal dysfunction.
- Spexin (SPX) is a peptide hormone with potential roles in metabolic regulation.
- Galanin receptor-2 (GALR-2) is implicated in various physiological processes, including potential modulation of renal function.
Purpose of the Study:
- To investigate the effect of spexin (SPX) on renal dysfunction in obese rats.
- To explore the underlying mechanisms of SPX's action, particularly its potential mediation via galanin receptor-2 (GALR-2).
Main Methods:
- Wistar male rats were divided into four groups: control, HFFD, HFFD + SPX, and HFFD + M871 (GALR-2 antagonist) + SPX.
- Evaluated parameters included urine volume, body mass index, Lee index, mean arterial blood pressure, renal function markers, lipid profile, glucose, insulin, and SPX levels.
- Assessed renal histopathology, immunohistochemistry, gene expression, and specific markers of oxidative stress, inflammation, apoptosis, and fibrosis.
Main Results:
- SPX treatment significantly mitigated HFFD-induced metabolic changes and renal dysfunction.
- SPX administration improved insulin resistance, dyslipidemia, and reduced oxidative stress, inflammation, apoptosis, and fibrosis in the renal tissue.
- The beneficial effects of SPX were observed to be mediated via the GALR-2 pathway.
Conclusions:
- Spexin (SPX) demonstrates a significant therapeutic potential in ameliorating obesity-related renal dysfunction.
- The mechanism involves the modulation of metabolic, inflammatory, and fibrotic pathways through GALR-2.
- SPX can be considered a promising agent for treating renal dysfunction associated with metabolic disorders.
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