Maternal Chronodisruption Throughout Pregnancy Impairs Glucose Homeostasis and Adipose Tissue Physiology in the Male Rat Offspring.

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Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague-Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3-4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100-200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.", "claims": [{"id": "claim-method", "statement": "LD and CPS differences in weight gain, food consumption, glycerol release, hormone levels, iGTT, iITT, and global methylation were analyzed by two-way repeated measures ANOVA and Bonferroni post-hoc test when group factor or interaction factor was significant (32).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34484111", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "LD and CPS differences in weight gain, food consumption, glycerol release, hormone levels, iGTT, iITT, and global methylation were analyzed by two-way repeated measures ANOVA and Bonferroni post-hoc test when group factor or interaction factor was significant (32)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. 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