Objective Canonical Wnt/β-catenin signaling is a well-studied endogenous regulator of mesenchymal cell fate determination, promoting osteoblastogenesis and inhibiting adipogenesis. However, emerging genetic evidence in humans links a number of Wnt pathway members to body fat distribution, obesity, and metabolic dysfunction, suggesting that this pathway also functions in adipocytes. Recent studies in mice have uncovered compelling evidence that the Wnt signaling pathway plays important roles in adipocyte metabolism, particularly under obesogenic conditions. However, complexities in Wnt signaling and differences in experimental models and approaches have thus far limited our understanding of its specific roles in this context. Methods To investigate roles of the canonical Wnt pathway in the regulation of adipocyte metabolism, we generated adipocyte-specific β-catenin ( β-cat ) knockout mouse and cultured cell models. We used RNA sequencing, ChIP sequencing, and molecular approaches to assess expression of Wnt targets and lipogenic genes. We then used functional assays to evaluate effects of β-catenin deficiency on adipocyte metabolism, including lipid and carbohydrate handling. In mice maintained on normal chow and high-fat diets, we assessed the cellular and functional consequences of adipocyte-specific β-catenin deletion on adipose tissues and systemic metabolism. Results We report that in adipocytes, the canonical Wnt/β-catenin pathway regulates de novo lipogenesis (DNL) and fatty acid monounsaturation. Further, β-catenin mediates effects of Wnt signaling on lipid metabolism in part by transcriptional regulation of Mlxipl and Srebf1 . Intriguingly, adipocyte-specific loss of β-catenin is sensed and defended by CD45 - /CD31 - stromal cells to maintain tissue-wide Wnt signaling homeostasis in chow-fed mice. With long-term high-fat diet, this compensatory mechanism is overridden, revealing that β-catenin deletion promotes resistance to diet-induced obesity and adipocyte hypertrophy and subsequent protection from metabolic dysfunction. Conclusions Taken together, our studies demonstrate that Wnt signaling in adipocytes is required for lipogenic gene expression, de novo lipogenesis, and lipid desaturation. In addition, adipose tissues rigorously defend Wnt signaling homeostasis under standard nutritional conditions, such that stromal-vascular cells sense and compensate for adipocyte-specific loss. These findings underscore the critical importance of this pathway in adipocyte lipid metabolism and adipose tissue function.

Although visceral adipocytes located within the body’s central core are maintained at approximately 37°C, adipocytes within bone marrow, subcutaneous, and dermal depots are found primarily within the peripheral shell and generally exist at cooler temperatures. Responses of brown and beige/brite adipocytes to cold stress are well studied; however, comparatively little is known about mechanisms by which white adipocytes adapt to temperatures below 37°C. Here, we report that adaptation of cultured adipocytes to 31°C, the temperature at which distal marrow adipose tissues and subcutaneous adipose tissues often reside, increases anabolic and catabolic lipid metabolism, and elevates oxygen consumption. Cool adipocytes rely less on glucose and more on pyruvate, glutamine, and, especially, fatty acids as energy sources. Exposure of cultured adipocytes and gluteal white adipose tissue (WAT) to cool temperatures activates a shared program of gene expression. Cool temperatures induce stearoyl-CoA desaturase-1 (SCD1) expression and monounsaturated lipid levels in cultured adipocytes and distal bone marrow adipose tissues (BMATs), and SCD1 activity is required for acquisition of maximal oxygen consumption at 31°C.

Objective Online patient portals become important during disruptions to in-person health care, like when cases of COVID-19 and other respiratory viruses rise, yet underlying structural inequalities associated with race, socio-economic status, and other socio-demographic characteristics may affect their use. We analyzed a population-based survey to identify disparities within the U.S. in access to online portals during the early period of COVID-19 in 2020. Materials and Methods The National Cancer Institute fielded the 2020 Health and Information National Trends Survey from February-June 2020. We conducted multivariable analysis to identify socio-demographic characteristics of U.S patients who were offered and accessed online portals, and reasons for nonuse. Results Less than half of insured adult patients reported accessing an online portal in the prior 12 months, and this was less common among patients who are male, are Hispanic, have less than a college degree, have Medicaid insurance, have no regular provider, or have no internet. Reasons for nonuse include: wanting to speak directly to a provider, not having an online record, concerns about privacy, and discomfort with technology. Discussion Despite the rapid expansion of digital health technologies due to COVID-19, we found persistent socio-demographic disparities in access to patient portals. Ensuring that digital health tools are secure, private and trustworthy would address some patient concerns that are barriers to portal access. Conclusion Expanding use of online portals requires explicitly addressing fundamental inequities to prevent exacerbating existing disparities, particularly during surges in cases of COVID-19 and other respiratory viruses that tax health care resources. Lay Summary Federal policies and investments by healthcare providers have increased the use of digital health technologies in recent years. Technologies like online patient portals may help manage limited health care resources during rising cases of COVID-19 and other respiratory viruses, yet underlying structural inequalities associated with race, socio-economic status, and other socio-demographic characteristics may mean they are not accessible to all patients. We find that those with fewer resources, based not only on socio-economic factors like education and Medicaid insurance, but also related to racially minoritized status and health care attributes like not having a regular provider or lacking high quality care, are less likely to access a portal. Our findings show that even when interventions like patient portals can help reduce the impact of a new risk, if they do not disrupt underlying resource differences that limit access, disparities will remain and may even grow.

One of the primary challenges facing synthetic biology is reconstituting a living system from its component parts. A particularly difficult landmark is reconstituting a self‐organizing system that can undergo autonomous chromosome compaction, segregation, and cell division. Here, we discuss how the syn3.0 minimal genome can inform us of the core self‐organizing principles of a living cell and how these self‐organizing processes can be built from the bottom up. The review underscores the importance of fundamental biology in rebuilding life from its molecular constituents.