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Abstract AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons.

The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.

IntroductionThe role of personality in shaping engagement with aesthetics in science has been almost entirely unexplored. Whereas artists and arts settings (e.g., museums) are well-studied from a psychological perspective, the practice of science has often been seen as purely rational or dry. In response, this study presents novel findings on the critical role of scientists’ individual differences, which shape their engagement with aesthetics, such as the frequency of their experiences of beauty, wonder, and awe in their scientific work.MethodsBased on a very large and representative four-country study of scientists in the fields of biology and physics (N = 3,092), this study analyzed the associations of Big Five personality traits among scientists with (i) dispositional aesthetics (DPES-awe), (ii) the frequency of aesthetic experiences in scientific work, and (iii) aesthetic sensitivity in science. These survey-weighted OLS regression models included extensive statistical controls for sociodemographic factors.ResultsAs hypothesized, openness is positively, and neuroticism is negatively linked with dispositional aesthetics, the frequency of aesthetic experiences in scientific work, and aesthetic sensitivity in science. Unexpectedly, agreeableness and conscientiousness (but not extraversion) are highly significant and strong predictors of the three trait and state aesthetic engagement variables.DiscussionThe aesthetic engagement and personality framework of this paper is empirically supported and demonstrates the importance of personality types of scientists in the practice of science. The unexpectedly strong association of agreeableness with aesthetic engagement points to the importance of cooperation, collaboration, and communication to maximize scientific creativity.