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Review
. 2019 Aug 12;11(8):1872.
doi: 10.3390/nu11081872.

Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

Adam Wróblewski  1 , Justyna Strycharz  2 , Ewa Świderska  2 , Karolina Drewniak  3 , Józef Drzewoski  4 , Janusz Szemraj  2 , Jacek Kasznicki  5 , Agnieszka Śliwińska  6
Affiliations
Review

Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

Adam Wróblewski et al. Nutrients. .

Abstract

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

Keywords: DNA methylation; fetal programming; gestational diabetes; histone modifications; insulin sensitivity; leptin; leptin resistance; metabolic disorders; microRNAs; obesity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Proposed model of miRNA participation in downstream signaling and regulation of leptin expression. miRNAs and negative outcomes are highlighted in green and blue, respectively. Associations are indicated by arrows (stimulation) and T-bars (inhibition). Actions related to boxes refer to all items inside the box. Arrows and T-bars which are crossed out mark the abrogation of the respective type of regulation. Associations were based on the leptin administration or the ob/ob model excluding those marked by asterisks (exclusively, the effect of miRNAs on leptin expression was measured, without prior manipulation of the leptin level). The figure was made using the PathVisio 3.3.0 free open-source software [53].
Figure 2
Figure 2
Leptin-mediated miRNA expression changes in adipocytes and during adipogenesis. miRNAs are highlighted in green. Associations are indicated by arrows (stimulation) and T-bars (inhibition). Actions related to boxes refer to all items inside the box. Associations were based on the results of the studies involving leptin administration excluding those marked by asterisks (miRNA knockdown experiments) or hash (targeting proved by reporter luciferase assay). The figure was made using the PathVisio 3.3.0 free open-source software [53].
Figure 3
Figure 3
Proposed model of leptin’s participation in perinatal programming. Negative outcomes are highlighted in blue. Associations based on leptin administration are indicated by arrows (stimulation) and T-bars (inhibition). Actions related to boxes refer to all items inside the box. Straight lines indicate correlations. The figure was made using the PathVisio 3.3.0 free open-source software [53].
See this image and copyright information in PMC

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