Adipocytes actively synthesize and secrete hormones, growth factors, and cytokines. Leptin [Gr. leptos, thin], a 16-kilodalton peptide hormone involved in the regulation of energy homeostasis, is exclusively secreted by adipocytes. Leptin inhibits food intake and loss of body weight and stimulates metabolic rate. Thus, leptin fulfills the criteria for a circulating satiety factor that controls food intake when the body’s store of energy is sufficient. Leptin also participates in an endocrine signaling pathway that communicates the energy state of adipose tissue to brain centers that regulate food uptake. It acts on the central nervous system by binding to specific receptors, mainly in the hypothalamus. In addition, leptin communicates the fuel state of adipocytes from fat-storage sites to other metabolically active tissues (i.e., from adipose tissue to muscle at a different site).
In addition to leptin, adipose tissue secretes other hormones, including angiotensinogen (AGE), adiponectin, and resistin, and produces steroid hormones (testosterone, estrogens, and glucocorticoids). AGE is synthesized in other tissues, including the liver; increased production of this peptide contributes to hypertension (elevation of blood pressure), which is a frequent complication of obesity. Sex hormones and glucocorticoids are not synthesized de novo; instead they are converted from inactive forms by specific enzymes expressed in adipocytes. These enzymes can therefore inﬂuence the sex steroid profiles of obese individuals. Obesity-increased secretion of growth factors (tumor necrosis factor a [TNF-a], transforming growth factor b [TGF-b], and insulinlike growth factor I [IGF-I]) and cytokines (interleukin 6 and prostaglandins) may be linked to metabolic  abnormalities and development of  diabetes. Table 9.1 presents a summary of the molecules produced by adipocytes and their functions.
Differentiation of Adipocytes
White adipocytes differentiate from mesenchymal stem cells under the control of PPAR/RXR transcription factors.
Early histologists debated whether adipose tissue was a specific tissue, distinct from connective tissue, or ordinary connective tissue in which fibroblasts store fat globules. The current consensus is that adipocytes are a specific cell type derived from undifferentiated mesenchymal stem cells associated with the adventitia of small venules (Fig. 9.1). Current evidence suggests that a transcription factor called peroxisome proliferator–activated receptor gamma (PPAR) in complex with the retinoid X receptor (RXR) play a critical role in adipocyte differentiation and initiation of lipid metabolism. It induces the maturation of early lipoblasts (adipoblasts) or preadipocytes into fat cells of white adipose tissue. Most of the PPAR target genes in adipose tissue influence lipogenic pathways and initiate the storage of triglycerides. Therefore, PPAR/RXR is regarded as the “master switch” regulator in the white adipocytes’ differentiation.
White adipose tissue begins to form midway through fetal development.
Lipoblasts initially develop from stromal-vascular cell along the small blood vessels in the fetus and are free of lipids. These cells are committed to becoming adipocytes at this early stage by expressing PPAR/RXR transcription factors. Collections of such cells are sometimes called primitive fat organs. They are characterized by proliferating early lipoblasts and proliferating capillaries. Lipid accumulation in lipoblasts produces the typical morphology of adipocytes.
Early lipoblasts look like fibroblasts but develop small lipid inclusions and a thin external lamina.