In mammals, the adipose tissues are contained in a multi-depot organ: the adipose organ. It consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, while many are white and correspond to white adipose tissue. The organ is rich of vessels and parenchymal nerve fibers, but their density is higher in the brown areas. White areas contain a variable amount of brown adipocytes and their number varies with age, strain and environmental conditions. All adipocytes of the adipose organ express a specific adrenoceptor: ss3AR. Recent data have stressed the plasticity of the adipose organ in adult animals, and in parallel with the cytological variations there are also vascular as well as neural variations. Of note, treatment of genetically and diet induced obese rats with ss3 adrenoceptor agonists ameliorate their pathological condition and this is accompanied by the appearance of brown adipocytes in white areas of the adipose organ. This drug-induced modification of the anatomy of the organ is also obtained by the treatment with PPARgamma agonists in rats and dogs. We have previously shown that the transformation of white adipose tissue into brown adipose tissue in rats treated with ss3 adrenoceptor agonists is due to a direct transformation of differentiated unilocular adipocytes (transdifferentiation). We recently also showed that the absence of ss3 adrenoceptors strongly depress this type of plasticity in the adipose organ. All together these experiments strongly suggest the possibility to modulate the plasticity of the adipose organ with therapeutic implications for obesity and related disorders.

The Adipose Organ

The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT a...

https://www.physiology.org/doi/pdf/10.1152/ajpendo.00600.2009

The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation.

Brown adipose tissue thermogenesis and obesity

Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.

Transdifferentiation properties of adipocytes in the adipose organ

Alpha- and beta-adrenergic induction of the expression of the uncoupling protein thermogenin in brown adipocytes differentiated in culture.

Human brown adipose cells in culture

Interscapular brown adipose tissue was removed from young rats, the cells isolated using collagenase, pelleted by centrifugation and cultured. Ultrastructural observations were made on these cells immediately after isolation and on Days 1, 2, 4, 10 and 14 of culture. The isolated cells show the typical submicroscopic features of cells in intact brown adipose tissue, i.e. a multivacuolar lipid depot and numerous typical mitochondria with dense cristae. However, as early as Day 1 of culture, the cells show degeneration of the typical mitochondria which are probably then extruded from the cells. Atypical mitochondria now begin to appear and become dominant on Day 4 of culture. By contrast, the typical multivacuolar shape of the lipid droplet does not change. Not even after prolonged periods of culture (2-4 weeks) is there any evidence of coalescence of the multivacuolar lipid depot. These findings are consistent with the possibility that the typical mitochondria of brown adipocytes depend on in vivo conditions, perhaps adrenergic innervation, while the multivacuolar characteristic of the lipid depot does not, and may be an intrinsic feature of the brown adipose cell.

Isolation and ultrastructural features of brown adipocytes in culture.

Several authors have not been able to find any antilipolytic effect of insulin in adipose tissue "in vitro". We investigated the possible role of cell size and/or age of donors on this phenomenon. The lipolytic rates (glycerol release per cell) were lower in the small cells of the 4-6 weeks old rats than in the larger cells of the 25-30 weeks old animals; however, the difference disappeared when the data were expressed per unit of cell surface area. Insulin (0.5-50 ng/ml) failed to inhibit both maximally and submaximally noradrenaline stimulated lipolysis in the adipocytes of the young rats, but its antilipolytic action was fully restored by using glucose-free medium. Therefore, at our experimental conditions, a glucose dependent factor, possibly involving the preferential hydrolysis of newly synthetized triglycerides, seems to blunt or to mask the insulin induced inhibition of glycerol release. Relatively higher rates of glucose metabolism and a lower lipolysis in small fat cells might explain the difference in the action of insulin on glycerol release in the adipose tissue of young rats as compared to the older ones.

L. Brunetti

Papers

Human brown adipose cells in culture

Isolation and ultrastructural features of brown adipocytes in culture.

Effect of insulin on lipolysis in adipose tissue of rats of different ages