Expanded adipose tissue mass increases the risk for many clinical conditions including diabetes, hypertension, coronary atherosclerotic heart disease, and some forms of cancer. Therefore, it is imperative that we understand the mechanisms by which fat pads expand. The enlargement of fat cells during the development of obesity has been previously hypothesized to be a triggering factor for the proliferation of new fat cells. There is now a preponderance of evidence that adipose tissue is a source of growth factors such as IGF-I, IGF binding proteins, TNF alpha, angiotensin II, and MCSF that are capable of stimulating proliferation. The relative importance of these autocrine/paracrine factors in the normal control of preadipocyte proliferation is unknown. In addition, the proliferative response of preadipocytes to the paracrine milieu is undoubtedly modulated by neural inputs to fat tissue and/or serum factors. Together, these multiple regulatory controls orchestrate overall and region-specific adipose tissue cellularity responses associated with the development of hyperplastic obesity. Both in vivo and in vitro studies are needed to understand the complex, interacting physiological mechanisms by which growth of this important organ is regulated.

Adipose tissue microcirculation is unique within the vascular system because of a capacity for this tissue to grow throughout most of adult life. A review of the microcirculation of adipose tissue has included a historical review of the early studies, which served as a foundation for later investigations on this topic, including basic hemodynamic measurements in mammalian adipose tissue. The various methods for measuring blood flow in white and brown adipose tissue are discussed with respect to studies of transport of substrates involved in adipose tissue metabolism. The role of innervation and vascular adrenergic receptors and the effects of diet and exercise on adipose tissue blood flow are also included. An in-depth analysis of the development of adipose tissue microvasculature indicates that angiogenesis often precedes adipogenesis. The clinical effects of hemodynamic adaptations to adipose tissue expansion are discussed in view of an epidemic increase in the prevalence of obesity and its co-morbidities. The recent discovery of sites of nuclear regulation of adipocyte differentiation, together with the identification of growth factors in adipose tissue, is an indication of the progress that is being made in the further understanding of molecular and cellular events that affect adipose tissue growth and, ultimately, adipose tissue microcirculation.

The quality and value of the carcass in domestic meat animals are reflected in its protein and fat content. Preadipocytes and adipocytes are important in establishing the overall fatness of a carcass, as well as being the main contributors to the marbling component needed for consumer preference of meat products. Although some fat accumulation is essential, any excess fat that is deposited into adipose depots other than the marbling fraction is energetically unfavorable and reduces efficiency of production. Hence, this review is focused on current knowledge about the biology and regulation of the important cells of adipose tissue: preadipocytes and adipocytes.

A review of adipose tissue angiogenesis includes the morphological and cytochemical development of adipose tissue vasculature and the concept of primitive fat organs. Spatial and temporal relationships between fetal vascular and fat cell development are discussed, including depot- and genetic-dependent arteriolar differentiation. The relationship between connective tissue deposition and elaboration of adipose tissue vasculature is discussed with respect to regulating adipocyte development in a depot-dependent manner. In vitro studies indicated that depot-dependent vascular traits may be attributable to intrinsic growth characteristics of adipose tissue endothelial cells. These studies indicate that adipogenesis may be regulated by factors that drive angiogenesis. Fundamental aspects of angiogenesis, including basement membrane breakdown, vasculogenesis, angiogenic remodeling, vessel stabilization, and vascular permeability were reviewed. Critical angiogenic factors include vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins (Ang), ephrins, matrix metalloproteinases, and the plasminogen enzymatic system. Vascular endothelial growth factor is the most critical factor because it initiates the formation of immature vessels and disruption of a single VEGF allele leads to embryonic lethality in mice. Expression of VEGF is influenced by hypoxia, insulin, growth factors, and several cytokines. Angiogenic factors secreted and/or produced by adipocytes or preadipocytes are discussed. Vascular endothelial growth factor expression and secretion by adipocytes is regulated by insulin and hypoxia, and is associated with adipose tissue accretion. Vascular endothelial growth factor accounts for most of the angiogenic activity of adipose tissue. The proposed role of leptin as an adipogenic factor is reviewed with respect to efficacy on various aspects of angiogenesis relative to other angiogenic factors. The VEGF and leptin genes are both hypoxia inducible, but potential links between VEGF and leptin gene expression have not been examined. Finally, several studies including a study of mice treated with antiangiogenic factors indicate that adipose tissue accretion can be controlled through the vasculature per se.

In vitro models have been invaluable in determining the mechanisms involved in adipocyte proliferation, differentiation, adipokine secretion and gene/protein expression. The cells presently available for research purposes all have unique advantages and disadvantages that one should be aware of when selecting cells. Established cell lines, such as 3T3-L1 cells, are easier and less costly to use than freshly isolated cells, even though freshly isolated cells allow for various comparisons such as the in vitro evaluation of different in vivo conditions that may not be possible using cell lines. Moreover, stem cells, transdifferentiated cells or dedifferentiated cells are relatively new cell models being evaluated for the study of adipocyte regulation and physiology. The focus of this brief review is to highlight similarities and differences in adipocyte models to aid in appropriate model selection and data interpretation for successful advancement of our understanding of adipocyte biology.

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In the present manuscript, the methods required to generate purified cultures of mature adipocytes, as well as stromal vascular cells, from the same isolation are detailed. Also, we describe the in vitro conditions for the dedifferentiation of the isolated mature adipocytes. These two types of cells may be used to reevaluate differences between presently available cellular models for lipogenesis/lipolysis and might provide a new cellular physiological system for studies utilizing the proliferative progeny from mature adipocyte dedifferentiation. Alternative possibilities to the dedifferentiation phenomenon are proposed, as this new area of research is novel.Abbreviations: DMEM -Dulbecco's modified Eagle medium; DMEM/F12 -1:1 ratio; Dulbecco's modified Eagle medium + Ham's F12; FBS -fetal bovine serum; HBSS -Hank's balanced salt solution; HS -horse serum; PBS -phosphate buffered saline, pH 7.08; PSG -pigskin gelatin; SC -satellite cell