PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity

Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular cells in white adipose tissue (WAT) and their potential to cause organ fibrosis. We show that a Nestin-Cre transgene targets perivascular cells (adventitial cells and pericyte-like cells) in WAT, and Nestin-GFP specifically labels pericyte-like cells. Activation of PDGFRα signaling in perivascular cells causes them to transition into ECM-synthesizing profibrotic cells. Before this transition occurs, PDGFRα signaling up-regulates mTOR signaling and ribosome biogenesis pathways and perturbs the expression of a network of epigenetically imprinted genes that have been implicated in cell growth and tissue homeostasis. Isolated Nestin-GFP+ cells differentiate into adipocytes ex vivo and form WAT when transplanted into recipient mice. However, PDGFRα signaling opposes adipogenesis and generates profibrotic cells instead, which leads to fibrotic WAT in transplant experiments. These results identify perivascular cells as fibro/adipogenic progenitors in WAT and show that PDGFRα targets progenitor cell plasticity as a profibrotic mechanism

Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies

Chemokine receptors on the defensive – the surprising role of CXCR4 in brown adipose tissue

Obesity, which is triggered by over-nutrition and supported by the excessive expansion of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence of type 2 diabetes, hypertension, cardiovascular disease and cancer. Since obesity-induced co-morbidities impose a significant financial burden on healthcare systems in Western societies, clear understanding of molecules and mechanisms supporting physiologic and pathologic activities of adipose tissue is mandatory. Abundant evidence shows that development of obesity is facilitated by a low-grade inflammation fueled by infiltration of pro-inflammatory leukocytes into white adipose tissue pads, which is in part mediated by chemokines and chemokine receptors. However, not all members of the chemokine system facilitate development of obesity. In this publication we highlight a surprising role of CXCR4 in fat cells where this chemokine receptor promotes energy expenditure and prevents excessive inflammatory leukocyte recruitment into adipose tissue, and by so doing, limits obesity

Dynamic coverage control design of multi-agent systems under ellipse sensing regions

summary:This paper studies the dynamic coverage control problem for cooperative region reconnaissance where a group of agents are required to reconnoitre a given region. The main challenge of this problem is that the sensing region of each agent is an ellipse. This modeling results in asymmetric(directed) interactions among agents. First, the region reconnaissance is formulated as a coverage problem, where each point in the given region should be surveyed until a preset level is achieved. Then, a coverage control law is designed that minimizes coverage performance index by finite switches between nominal control laws and perturbation control law. Finally, numerical simulations are provided to indicate the efficiency of the proposed control law

Bone marrow dysfunction in mice lacking the cytokine receptor gp130 in endothelial cells

In vitro studies suggest that bone marrow endothelial cells contribute to multilineage hematopoiesis, but this function has not been studied in vivo. We used a Cre/loxP-mediated recombination to produce mice that lacked the cytokine receptor subunit gp130 in hematopoietic and endothelial cells. Although normal at birth, the mice developed bone marrow dysfunction that was accompanied by splenomegaly caused by extramedullary hematopoiesis. The hypocellular marrow contained myeloerythroid progenitors and functional repopulating stem cells. However, long-term bone marrow cultures produced few hematopoietic cells despite continued expression of gp130 in most stromal cells. Transplanting gp130-deficient bone marrow into irradiated wild-type mice conferred normal hematopoiesis, whereas transplanting wild-type bone marrow into irradiated gp130-deficient mice did not cure the hematopoietic defects. These data provide evidence that gp130 expression in the bone marrow microenvironment, most likely in endothelial cells, makes an important contribution to hematopoiesis

Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies