Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors.

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes.

iTAG-RNA Isolates Cell-Specific Transcriptional Responses to Environmental Stimuli and Identifies an RNA-Based Endocrine Axis.

Biofluids contain various circulating cell-free RNAs (ccfRNAs). The composition of these ccfRNAs varies among biofluids. They constitute tantalizing biomarker candidates for several pathologies and have been demonstrated to be mediators of cellular communication. Little is known about their function in physiological and developmental settings, and most works are limited to in vitro studies. Here, we develop iTAG-RNA, a method for the unbiased tagging of RNA transcripts in mice in vivo. We use iTAG-RNA to isolate hepatocytes and kidney proximal epithelial cell-specific transcriptional responses to a dietary challenge without interfering with the tissue architecture and to identify multiple hepatocyte-secreted ccfRNAs in plasma. We also identify specific transfer of liver-derived ccfRNAs to adipose tissue and skeletal muscle, where they likely constitute a buffering system to maintain lipid homeostasis under acute high-fat-diet feeding. Our findings directly demonstrate in vivo transfer of RNAs between tissues and highlight its implications for endocrine signaling and homeostasis.