Effect of spexin on renal dysfunction in experimentally obese rats: potential mitigating mechanisms via galanin receptor-2

El-Saka, Mervat H; Gheit, Rehab E. Abo El; Saadany, Amira El; Alghazaly, Ghada Mahmoud; Marea, Karima E; Madi, Nermin M.

doi:10.1080/13813455.2021.1887265

Cited by 23 publications

(11 citation statements)

References 41 publications

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“…However, most research has been focused on adipose tissue, the liver, the pancreas or the kidneys [ 6 , 7 , 8 ]. It has been shown, inter alia, that spexin is able to regulate lipogenesis and lipolysis processes in adipocytes [ 9 ], prevent inflammation in fat tissue [ 10 ], regulate insulin secretion [ 11 ], mitigate the metabolic changes and renal dysfunction accompanying obesity [ 12 ] and exhibit cardioprotective properties [ 13 ]. Despite the increasing knowledge on the role of SPX in the metabolism of metabolic disorders such as diabetes or obesity, there are still some pieces required to solve this puzzle.…”

Section: Introductionmentioning

confidence: 99%

Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo

Leciejewska

Pruszyńska‐Oszmałek

Mielnik

et al. 2021

Genes

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SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

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Section: Introductionmentioning

confidence: 99%

Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo

Leciejewska

Pruszyńska‐Oszmałek

Mielnik

et al. 2021

Genes

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“…19 While SPX improved these parameters, M871 suppressed enhancement of these metabolic markers induced by SPX. 19 Considering the cellular action elicited by SPX, much more study is needed to unveil the signaling pathways activated by SPX.…”

Section: Mechanism Of Actionmentioning

confidence: 90%

“…12 Supporting the conclusion that SPX activates GAL2R and modulates cellular functions, it was recently shown that high fat/fructose (HFF) diet-induced metabolic changes such as increased body weight, glucose and insulin, and homeostatic model assessment-insulin resistance (HOMA-IR) were reversed by SPX treatment. 19 While SPX improved these parameters, M871 suppressed enhancement of these metabolic markers induced by SPX. 19 Considering the cellular action elicited by SPX, much more study is needed to unveil the signaling pathways activated by SPX.…”

Section: Mechanism Of Actionmentioning

confidence: 90%

“…37 In DIO rats, SPX decreased IFN and IL-10 in kidney tissue, while it increased monocyte chemoattractant protein-1 (MCP1) expression. 19 Furthermore, SPX treatment decreased IL-33 gene expression in kidney tissue in adenine-induced CRF in rats. 56 In the same experiment, SPX treatment reduced serum IL-5, granulocyte colony-stimulating factor (G-CSF), and IFN-γ levels.…”

Section: Spx Modulates Inflammatory Responsementioning

confidence: 96%

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Impact of spexin on metabolic diseases and inflammation: An updated minireview

Türkel

Memi

Yazgan

2022

Exp Biol Med (Maywood)

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Spexin (SPX) is a 14 amino acid length peptide hormone which was discovered using bioinformatic tools. It is extensively expressed in central and peripheral tissues and secreted into circulation in response to metabolic stress. Recent studies revealed that SPX acts as a multifunctional peptide in various metabolic processes such as body weight, food intake, energy balance, glucose and lipid metabolism, lipid storage, salt–water balance, and arterial blood pressure. Endogenous SPX is sensitive to metabolic changes, and circulating levels of SPX have been shown to be reduced in chronic diseases such as obesity, diabetes, and insulin resistance. Moreover, in fish and rodent models, systemic SPX treatment has positive effects on metabolism including reduced food intake, fat mass, lipid accumulation, and inflammation, improved insulin sensitivity, energy expenditure, and organ functions which are underlying mechanisms in diseases. Taken together, these findings suggest that SPX is a potential drug target for the development of new pharmacological strategies to cure metabolic diseases. This review focuses on metabolo-protective properties of SPX and discusses novel insights into the biology and mechanism of SPX in the pathogenesis of diabetes, obesity, non-alcoholic fatty liver disease, metabolic syndrome, polycystic ovary syndrome, cardiovascular diseases, and kidney diseases, which are considerable global health problems.

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“…In addition, it is plausible that the lower levels of galanin will upregulate the expression of the GALR2 located in the hypothalamus, which may, in turn, stimulate the GALR2-mediated signaling pathways in the hypothalamus, which is known to promote systemic glucose metabolism and energy homeostasis [1,19,20,28]. Activated GALR2 significantly increased GLUT4 expression in skeletal muscles, suggesting that activation of central GALR2 mediates the galanin roles to promote insulin sensitivity in the skeletal muscles [12,19,20,26,55]. Injection with a GALR2 agonist, M1145, into the lateral hypothalamus of mice might restore the ability of leptin to suppress overeating of high-fat/high-sucrose foods, suggesting that activation of central GALR2 mediates the promoting effect of galanin on leptin sensitivity in the lateral hypothalamus [33].…”

Section: Discussionmentioning

confidence: 99%

Time-restricted feeding prevents metabolic diseases through the regulation of galanin/GALR1 expression in the hypothalamus of mice

et al. 2021

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Purpose Time-restricted feeding (TRF) reverses obesity and insulin resistance, yet the central mechanisms underlying its beneficial effects are not fully understood. Recent studies suggest a critical role of hypothalamic galanin and its receptors in the regulation of energy balance. It is yet unclear whether TRF could regulate the expression of galanin and its receptors in the hypothalamus of mice fed a high-fat diet. Methods To test this effect, we subjected mice to either ad lib or TRF of a high-fat diet for 8 h per day. After 4 weeks, galanin and many neuropeptides associated with the function of metabolism were examined. ResultsThe present findings showed that mice under TRF consume equivalent calories from a high-fat diet as those with ad lib access, yet are protected against obesity and have improved glucose metabolism. Plasma galanin, orexin A, irisin and adropin levels were significantly reversed by TRF regimen. Besides, TRF regimen reversed the progression of metabolic disorders in mice by increasing GLUT4 and PGC-1α expression in skeletal muscles. Moreover, the levels of galanin and GALR1 expression were severely diminished in the hypothalamus of the TRF mice, whereas GALR2 was highly expressed. Conclusions TRF diminished galanin and GALR1 expression, and increased GALR2 expression in the hypothalamus of mice fed a high-fat diet. The current studies provide additional evidence that TRF is effective in improving HFD-induced hyperglycemia and insulin resistance in mice, and this effect could be associated with TRF-induced changes of the galanin systems in the hypothalamus. Level of evidence No level of evidence, animal studies Keywords Time-restricted feeding • Galanin • Obesity • GALR1 • GALR2 Jingjing Sun and Yuqing She are co-first author.

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Effect of spexin on renal dysfunction in experimentally obese rats: potential mitigating mechanisms via galanin receptor-2

Cited by 23 publications

References 41 publications

Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo

Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo

Impact of spexin on metabolic diseases and inflammation: An updated minireview

Time-restricted feeding prevents metabolic diseases through the regulation of galanin/GALR1 expression in the hypothalamus of mice

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