Dexamethasone treatment alters insulin, leptin, and adiponectin levels in male mice as observed in DIO but does not lead to alterations of metabolic phenotypes in the offspring

Abstract

Epigenetic inheritance (EI) of metabolic phenotypes via the paternal lineage has been shown in rodent models of diet-induced obesity (DIO). However, the factors involved in soma-to-germline information transfer remain elusive. Here, we address the role of alterations in insulin, leptin, and adiponectin levels for EI of metabolic phenotypes by treating C57BL/6NTac male mice (F0) with the synthetic glucocorticoid dexamethasone and generating offspring (F1) either by in vitro fertilization or by natural fecundation. Dexamethasone treatment slightly alters F0 body composition by increasing fat mass and decreasing lean mass, and significantly improves glucose tolerance. Moreover, it increases insulin and leptin levels and reduces adiponectin levels in F0 fathers as observed in mouse models of DIO. However, these paternal changes of metabolic hormones do not alter metabolic parameters, such as body weight, body composition and glucose homeostasis in male and female F1 mice even when these are challenged with a high-fat diet. Accordingly, sperm transcriptomes are not altered by dexamethasone treatment. Our results suggest that neither increased glucocorticoid, insulin, and leptin levels, nor decreased adiponectin levels in fathers are sufficient to confer soma-to-germline information transfer in EI of obesity via the paternal lineage.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-015-9616-5) contains supplementary material, which is available to authorized users.

CIAFIS – Congresso Internacional de Atividade Física, Nutrição e Saúde

“…However, no significant difference in body weight was observed in the SD and TD groups between the first and last day. These results were similar to those of Barel et al (2010) who used the treadmill running model in animals and demonstrated that after 70 days of intervention, the training did not promote adjustments in the body weights of animals In this study, the use of glucocorticoids was associated with increased fat mass and decreased lean body mass in the body composition (Bönisch et al, 2016;Hochberg et al, 2015). Physical exercise plays a role in minimizing these effects by reducing fat mass and increasing muscle mass (Eguchi et al, 2008).…”

Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance

“…Adipose tissues are endocrine organs that secrete pro- or anti-inflammatory adipokines as well as adipokines involved in metabolic regulations. A high level of GC impacts the secretion of leptin and adiponectin by the adipose tissue [ 106 ]. As a feedback loop, leptin and adiponectin modulate the GC production by the HPA [ 107 ].…”

Single paternal Dexamethasone challenge programs offspring metabolism and reveals circRNAs as novel candidates in RNA-mediated inheritance

“…While four (Petropoulos, Matthews and Szyf, 2014;Short et al, 2016;Wu et al, 2016;Cartier et al, 2018) out of five (Bönisch et al, 2016) previous studies did report phenotypic effects following chronic paternal Dex exposure, only two assessed sperm small RNAs to associate the alterations to the sperm RNA payload (Bönisch et al, 2016;Cartier et al, 2018) yielding conflicting outcomes. These differences might be due to inconsistent life stages (adulthood versus gestational), sperm collection (swim up, somatic lysis, or no purification) and/or dosage of exposure.…”