Gregoire, Francine M., Cynthia M. Smas, and Hei Sook Sul. Understanding Adipocyte Differentiation. Physiol. Rev. 78: 783–809, 1998. — The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyt...

Understanding Adipocyte Differentiation

https://www.cell.com/cell/pdf/S0092-8674(13)01546-8.pdf

What We Talk About When We Talk About Fat

Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. ...

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Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells Physiological and Therapeutic Perspectives

Adipose tissue evolved to efficiently store energy for times of caloric restriction. The large caloric excess common in many Western diets has negated the need for this thrifty function, leaving adipose tissue ill-equipped to handle this increased load. An excess of adipose tissue increases risk for a number of conditions including coronary artery disease, hypertension, dyslipidemias, type 2 diabetes, and even cancer. Indeed, the ability of the adipocyte to function properly when engorged with lipid can lead to lipid accumulation in other tissues, reducing their ability to function and respond normally. The role of adipose tissue as an endocrine organ capable of secreting a number of adipose tissue-specific or enriched hormones, known as adipokines, is gaining appreciation. The normal balance of these adipose tissue secretory proteins is perturbed in obesity. Paradoxically, the lack of normal adipose tissue, as seen in cases of lipodystrophy and lipoatrophy, is also associated with pathologic sequelae sim...

Minireview: The adipocyte - At the crossroads of energy homeostasis, inflammation, and atherosclerosis

Proliferation of blood vessels is a process necessary for the nonnal growth and development of tissue (36). In the adult, angiogenesis occurs infrequently. Exceptions are found in the female reproductive system, where angiogenesis occurs in the follicle during its development, in the corpus luteum during ovulation, and in the placenta after pregnancy. These periods of angiogenesis are relatively brief and tightly regulated. Nonnal angiogenesis also occurs as part of the body's repair processes, e.g. in the healing of wounds and fractures. By contrast, uncontrolled angiogenesis can often be pathological. For example, the growth of solid tumors depends on vascularization (37), and in diabetic retinopathy vascularization of the retina often leads to blindness. Given the physiologic and pathological importance of angiogenesis, much effort in the last twenty years has been devoted to the isolation, characteriza­ tion, and purification of factors that can either stimulate or inhibit an­ giogenesis. Several bioassays have been developed to measure angiogenesis. The most common ones are endothelial cell migration (47) and proliferation (38) in vitro, and capillary growth in vivo in the developing chick chorioallantoic membrane (CAM) (4) and the cornea (45). The goal of this review is to describe those stimulators and inhibitors of angiogenesis that have been best-characterized.

Regulators of angiogenesis.

1-Butyryl-glycerol: a novel angiogenesis factor secreted by differentiating adipocytes.

We have examined the cellular mechanisms by which heparin potentiates the ability of 3T3-adipocytes to stimulate the formation of new blood vessels. Both anticoagulant and non-anticoagulant heparin species enhanced the angiogenic activity of adipocyte-secreted products in the chick chorioallantoic membrane assay, indicating that the angiotropic effect of this glycosaminoglycan is independent of its effect on the coagulation cascade. Heparin alone was unable to produce a neovascular response. The ability of heparin to modulate three endothelial functions in vitro thought to be related to angiogenesis were examined: protease activity, motility, and mitogenesis. Heparin caused a 100% increase in the adipocyte-induced stimulation of endothelial cell plasminogen activator activity and motility, but had no effect on proliferation. The enhancement of plasminogen activator and chemoattractant activities had a similar ED50 (1-2 micrograms/ml) and optimum dose (10-30 micrograms/ml). When we examined the direct effect of heparin on the activity of two distinct plasminogen activator enzymes--urokinase and tissue-type--a dual action of heparin was observed: tissue-type enzyme activity was stimulated 100% by heparin at 10 micrograms/ml, whereas urokinase activity was inhibited by 77% at this dose. These data suggest that heparin potentiates angiogenesis in vivo by stimulating endothelial cell plasminogen activator, motility, or both. Our results further suggest that for adipocyte-induced blood vessel formation, in contrast to other angiogenesis systems, heparin does not appear to affect the mitogenic activity.

Arbetta M. Kambe

Papers

1-Butyryl-glycerol: a novel angiogenesis factor secreted by differentiating adipocytes.

Heparin potentiation of 3T3-adipocyte stimulated angiogenesis: Mechanisms of action on endothelial cells