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Catecholamines promote lipolysis both in brown and white adipocytes, whereas the same stimuli preferentially activate thermogenesis in brown adipocytes. Molecular mechanisms for the adipose-selective activation of thermogenesis remain poorly understood. Here, we employed quantitative phosphoproteomics to map global and temporal phosphorylation profiles in brown, beige, and white adipocytes under β3-adrenenoceptor activation and identified kinases responsible for the adipose-selective phosphorylation profiles. We found that casein kinase2 (CK2) activity is preferentially higher in white adipocytes than brown/beige adipocytes. Genetic or pharmacological blockade of CK2 in white adipocytes activates the thermogenic program in response to cAMP stimuli. Such activation is largely through reduced CK2-mediated phosphorylation of class I HDACs. Notably, inhibition of CK2 promotes beige adipocyte biogenesis and leads to an increase in whole-body energy expenditure and ameliorates diet-induced obesity and insulin resistance. These results indicate that CK2 is a plausible target to rewire the β3-adrenenoceptor signaling cascade that promotes thermogenesis in adipocytes.

Cyanobacterial blooms in lakes of low nutrient status are recent ecological surprises. Culling of planktivorous fish may help suppress phytoplankton blooms via a trophic cascade effect. To test this hypothesis, we conducted a 90-day experiment adjacent to a shallow oligomesotrophic lake increasingly beset by midsummer cyanobacterial blooms in the presence of high abundances of minnows and sparse herbivorous zooplankton. The single-factor ([+ or -] three spottail shiners, Notropis hudsonius) experimental design was replicated 10 times for a total of twenty 1200 L capacity mesocosms. Contrary to the trophic cascade hypothesis, minnow removal decreased the abundance of bosminids capable of grazing cyanobacteria. Nevertheless, removal of the minnows significantly both suppressed phytoplankton biomass and offset the development of cyanobacteria, such as Gloeotrichia echinulata. Lower concentrations of phosphorus and nitrogen in the fishless relative to stocked mesocosms best explained these differences in the phytoplankton community. Our findings highlight how fisheries management practices that enhance minnow populations in lakes of low productivity may inadvertently contribute to cyanobacterial blooms through increased nutrient cycling. Les proliferations de cyanobacteries dans des lacs pauvres en nutriments sont des evenements ecologiques recents surprenants. L'elimination de poissons planctonivores pourrait aider a reduire les proliferations de phytoplancton par un effet de cascade trophique. Pour verifier cette hypothese, nous avons mene une experience de 90 jours attenante a un lac oligomesotrophe peu profond faisant de plus en plus l'objet de proliferations estivales de cyanobacteries en presence d'une grande abondance de menes et de zooplancton herbivore peu abondant. Le plan experimental monofactoriel ([+ or -] trois queues a tache noire, Notropis hudsonius) a ete reproduit 10 fois pour un total de vingt mesocosmes d'une capacite de 1200 L. Contrairement aux predictions decoulant de l'hypothese de la cascade trophique, le retrait de menes a entraine une baisse de l'abondance de bosminides capables de se nourrir de cyanobacteries. Le retrait des menes a entraine toutefois une baisse significative de la biomasse de phytoplancton et limite le developpement de cyanobacteries comme Gloeotrichia echinulata. De plus faibles concentrations de phosphore et d'azote dans les mesocosmes exempts de poissons comparativement aux mesocosmes empoissonnes expliquent le mieux ces differences dans la communaute de phytoplancton. Nos constatations soulignent le fait que des pratiques de gestion des peches qui accroissent les populations de menes dans les lacs de faible productivite, en intensifiant le cycle des elements nutritifs, pourraient participer a des proliferations de cyanobacteries. [Traduit par la Redaction], Introduction Cyanobacterial blooms in freshwater ecosystems have long been associated with eutrophic conditions (Smith and Schindler 2009), but cyanobacteria are frequently also found in less productive lakes (Carey et al. [...]

Type 1 diabetes mellitus (T1DM) increases the risk of atherosclerotic cardiovascular disease (CVD) in humans by poorly understood mechanisms. Using mouse models of T1DM-accelerated atherosclerosis, we found that relative insulin deficiency, rather than hyperglycemia, elevated levels of apolipoprotein C3 (APOC3), an apolipoprotein that prevents clearance of triglyceride-rich lipoproteins (TRLs) and their remnants. We then showed that serum APOC3 levels predict incident CVD events in subjects with T1DM in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. To explore underlying mechanisms, we examined the impact of Apoc3 antisense oligonucleotides (ASOs) on lipoprotein metabolism and atherosclerosis in a mouse model of T1DM. Apoc3 ASO treatment abolished the increased hepatic expression of Apoc3 in diabetic mice, resulting in lower levels of TRLs, without improving glycemic control. APOC3 suppression also prevented arterial accumulation of APOC3-containing lipoprotein particles, macrophage foam cell formation, and accelerated atherosclerosis in diabetic mice. Our observations demonstrate that relative insulin deficiency increases APOC3 and that this results in elevated levels of TRLs and accelerated atherosclerosis in a mouse model of T1DM. Because serum levels of APOC3 predicted incident CVD events in the CACTI study, inhibition of APOC3 might reduce CVD risk in patients with T1DM., Introduction Atherosclerotic cardiovascular disease (CVD) is a major cause of morbidity and mortality in subjects with type 1 diabetes mellitus (T1DM) (1). Although some results suggest that CVD risk associated [...]

Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.

Insulin resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment, and disease pathology, the genetic basis of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates. Our results show dramatic variation in IR among strains of mice and widespread differences between sexes that are dependent on genotype. We uncover more than 15 genome-wide significant loci and validate a gene, Agpat5, associated with IR. We also integrate plasma metabolite levels and global gene expression from liver and adipose tissue to identify metabolite quantitative trait loci (mQTL) and expression QTL (eQTL), respectively. Our results provide a resource for analysis of interactions between diet, sex, and genetic background in IR.

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.

There is growing consensus regarding the effectiveness of active-learning pedagogies in college science courses. Less is known about ways that student-level factors contribute to positive outcomes in these contexts. The present study examines students' (N = 245) trust in the instructor--defined as perceptions of their instructor's understanding, acceptance, and care--and students' attitudes toward learning within an anatomy and physiology course featuring active learning. Analyses indicate that student trust of instructor and students' views of their own intelligence are both associated with student commitment to, and engagement in, active learning. Student-reported trust of the instructor corresponded to final grade, while students' views of their own intelligence did not. In an active-learning context in which students are more fully engaged in the learning process, student trust of the instructor was an important contributor to desired student outcomes.

Place-based education incorporates local communities into school curriculum, recognizing the importance of local traditions, communities, and ecosystems, and emphasizing content that has reference to community life and local ecology. One elementary art teacher worked to connect place to her own artistic identity and to her work teaching elementary art. She wondered if her students might use art as a method of inquiry to explore how place contributed to their sense of identity. She experimented with blurring the lines between teacher and artist. As she discussed her own artwork and how her artistic investigations connected to her identity and sense of place, she learned that her students had many similar experiences. To develop ideas about place and its connection with identity, she and her 5th graders collaborated on four paintings that functioned as a study of community and place. After six months of students' classroom experiences and discussions of the conceptual aspects of artmaking, identity, and connections to the places they lived, their investigation of place and identity culminated in an art show and permanent installation in the school hallways and an exhibit at the teacher's university.

Innovation and learning come together in a vibrant manner during dynamic arts education classes led by teachers who understand the importance of collaboration and student improvisation.

The LXR-regulated E3 ubiquitin ligase IDOL controls LDLR receptor stability independent of SREBP and PCSK9, but its relevance to plasma lipid levels is unknown. Here we demonstrate that the effects of the LXR-IDOL axis are both tissue and species specific. In mice, LXR agonist induces Idol transcript levels in peripheral tissues but not in liver, and does not change plasma LDL levels. Accordingly, Idol-deficient mice exhibit elevated LDLR protein levels in peripheral tissues, but not in the liver. By contrast, LXR activation in cynomolgus monkeys induces hepatic IDOL expression, reduces LDLR protein levels, and raises plasma LDL levels. Knockdown of IDOL in monkeys with an antisense oligonucleotide blunts the effect of LXR agonist on LDL levels. These results implicate IDOL as a modulator of plasma lipid levels in primates and support further investigation into IDOL inhibition as a potential strategy for LDL lowering in humans.

Professional workshops aimed at increasing student diversity typically urge college-level science, technology, engineering, and math (STEM) educators to implement inclusive teaching practices. A model of the process by which educators adopt such practices, and the relationship between adoption and 2 ideologies of diversity is tested here. One ideology, colorblindness, downplays differences based on gender or color. The other, multiculturalism, embraces differences. Pathway modeling revealed reliable, discrete steps in the process of adoption. Independently, greater endorsement of colorblindness predicted adoption of fewer inclusive teaching practices, and multiculturalism predicted adoption of more practices. These findings inform national-level intervention efforts about the process by which educators adopt inclusive teaching practices, and suggest that interventions might consider educators' personal beliefs and approaches to diversity.

In contemporary life and education, the local is marginalized in favor of large-scale economies of consumption that are indifferent to ecological concerns. The consequences of neglecting local human and natural communities include a degraded habitat, loss of wilderness, alienation, rootlessness, and lack of connection to communities. Place-based education responds to this indifference to local ecological concerns by grounding student learning in the experiences of their own lives, communities, and regions. Critical place-based pedagogy broadens the scope of place-based learning by incorporating critical theory into the curriculum of the local. This article describes a critical pedagogy of place as a prelude to describing contemporary art that is involved with ecological and social issues. Works of contemporary artists that are responsive to the ecology of local places and culture will be explored as examples of collaboration between artistic and scientific approaches. These artists suggest possibilities for the educator to create a critical pedagogy about place and to resist the isolation of the classroom from vital issues of community and ecology. The intersection of critical theory, place-based learning, and art education provides a robust framework for the theory and practice of education concerned with ecological issues.