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Leptin modulates gene expression in the heart, cardiomyocytes and the adipose tissue thus mitigating LPS-induced damage
- Source :
- Experimental Cell Research. 404:112647
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Leptin is an adipokine of pleiotropic effects linked to energy metabolism, satiety, the immune response, and cardioprotection. We have recently shown that leptin causally conferred resistance to myocardial infarction-induced damage in transgenic αMUPA mice overexpressing leptin compared to their wild type (WT) ancestral mice FVB/N. Prompted by these findings, we have investigated here if leptin can counteract the inflammatory response triggered after LPS administration in tissues in vivo and in cardiomyocytes in culture. The results have shown that LPS upregulated in vivo and in vitro all genes examined here, both pro-inflammatory and antioxidant, as well as the leptin gene. Pretreating mice with leptin neutralizing antibodies further upregulated the expression of TNFα and IL-1β in the adipose tissue of both mouse types, and in the αMUPA heart. The antibodies also increased the levels of serum markers for cell toxicity in both mouse types. These results indicate that under LPS, leptin actually reduced the levels of these inflammatory-related parameters. In addition, pretreatment with leptin antibodies reduced the levels of HIF-1α and VEGF mRNAs in the heart, indicating that under LPS leptin increased the levels of these mRNAs. In cardiomyocytes, pretreatment with exogenous leptin prior to LPS reduced the expression of both pro-inflammatory genes, enhanced the expression of the antioxidant genes HO-1, SOD2 and HIF-1α, and lowered ROS staining. In addition, results obtained with leptin antibodies and the SMLA leptin antagonist indicated that endogenous and exogenous leptin can inhibit leptin gene expression. Together, these findings have indicated that under LPS, leptin concomitantly downregulated pro-inflammatory genes, upregulated antioxidant genes, and lowered ROS levels. These results suggest that leptin can counteract inflammation in the heart and adipose tissue by modulating gene expression.
- Subjects :
- Leptin
Lipopolysaccharides
0301 basic medicine
medicine.medical_specialty
Transgene
SOD2
Gene Expression
Adipose tissue
Adipokine
Mice, Transgenic
Inflammation
Biology
03 medical and health sciences
0302 clinical medicine
Internal medicine
Gene expression
medicine
Animals
Myocytes, Cardiac
digestive, oral, and skin physiology
Cell Biology
030104 developmental biology
Endocrinology
Adipose Tissue
030220 oncology & carcinogenesis
Tumor necrosis factor alpha
medicine.symptom
Energy Metabolism
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 404
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....5e766e778c2e68a742d1336fe9677d65
- Full Text :
- https://doi.org/10.1016/j.yexcr.2021.112647