Abstract
Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. 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.
Highlights
At present, according to the European Foundation for the improvement of living and working conditions and the US Department of Labor, approximately 20% of the worldwide workforce is employed under shift work schedule [1, 2], increasing a risk of early onset of a series of noncommunicable diseases (NCD), like metabolic syndrome, obesity, and cardiovascular diseases [1, 3,4,5]
Considering that a clear relationship has been established for an adverse intrauterine milieu with chronic disease later in life [references in [36, 37]], we tested the hypothesis that gestational chronodisruption (CPS conditions) translates into long-term detrimental effects on glucose homeostasis and adipose tissue physiology, increasing the negative impact of high-fat diet (HFD) as a cardiometabolic challenge during adulthood in the male offspring
We found the impact of CPS on adipose tissue recruitment and function under standard diet that were enhanced by the HFD challenge
Summary
At present, according to the European Foundation for the improvement of living and working conditions and the US Department of Labor, approximately 20% of the worldwide workforce is employed under shift work schedule [1, 2], increasing a risk of early onset of a series of noncommunicable diseases (NCD), like metabolic syndrome, obesity, and cardiovascular diseases [1, 3,4,5] In this regard, compelling evidence in human and animal models support the idea that chronodisruption (i.e., disturbance of internal temporal order, essentially circadian, of endocrinology, physiology, metabolism, and behavior) might be a link between NCD and shift work schedule. New epidemiological studies add more evidence about the potential deleterious effects of gestational chronodisruption in human, conducting studies with more controlled conditions is imperative [5, 13, 14]
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