Sex Steroid Biosynthesis in White Adipose Tissue

White Adipose Tissue. General Concepts

White adipose tissue has long been considered a mere storage site for lipids and therefore an energetic reservoir for the maintenance of vital cell functions. When a fall in glucose occurs, lipolysis leads to the release of fatty acids for use by a variety of tissues such as muscle, liver and kidney. Partial oxidation of fatty acids also generates ketones, which serve as an alternate fuel source for the brain and other tissues. Conversely, an increase in glucose and lipids results in increased adipose fatty acid transport and lipogenesis. Fat metabolism depends on energy requirements and is regulated by nutrient, neural and hormonal signals [1].

Obesity and its adverse health consequences constitute an upcoming global epidemic in developed countries that has attracted the attention of the biomedical research community and national health care systems for both scientific and economic reasons. Although it is well-known that obesity prejudices health, it has been recognised that not all patients develop the same metabolic risk profile. While this profile is quite normal in some individuals, severe complications such as insulin resistance, atherogenic dyslipidaemia, type 2 diabetes, hypertension and cardiovascular disease may develop in others. Many studies conducted in the last 20 years have revealed that considerable metabolic heterogeneity exists among various adipose tissue depots, with abdominally obese patients being the subgroup with the highest risk of complications.

The discovery of leptin in the mid-1990s [2] [3] changed the view of adipose tissue to that of a tissue with significant endocrine functions. This secreted circulating factor, known as leptin, is encoded by the ob gene [2], and functions as the signal that reports the state of the body’s energy stores to the brain. Although it is mainly expressed in adipose tissue, low levels of leptin have also been detected in the placenta, skeletal muscle, gastric and mammary epithelium, as well as brain [4] [5] [6]. Leptin has a relative mass of 16 kDa, a helical structure similar to cytokines, and is highly conserved among mammals. Adipose tissue and plasma leptin concentrations are dependent on the amount of energy stored as fat, as well as energy balance status. Leptin is up-regulated by insulin, glucocorticoids, acute infection and pro-inflammatory cytokines, and down-regulated by cold exposure, adrenergic stimulation, GH, thyroid hormone, melatonin and smoking [4] [5] [6]. Leptin expression displays a dimorphic pattern by gender since it is higher in females than in males, due in part to its inhibition by androgens and stimulation by oestrogens [7]. Mutations in the ob gene causing total leptin deficiency may produce hyperphagia, morbid obesity, diabetes, a variety of neuroendocrine abnormalities and autonomic and immune dysfunction [4].

Adipose tissue functions as the major storage depot for triglycerides, but is also an active endocrine organ that senses metabolic signals and secretes hormones that affect the whole body’s energy homeostasis [8] [9] [10]. Apart from leptin, adipocytes are able to secrete tumour necrosis factor alpha [11], plasminogen activator inhibitor (PAI-1) [12], adipsin [13], resistin [14] and adiponectin [15] [16] [17] [18] [19], collectively known as adipocytokines [20]. Other hormones such as angiotensinogen [21] and angiotensin II (AII) [22] have also been described in adipose tissue. Some authors have related the presence of AII with control of adiposity through regulation of lipid synthesis and storage in adipocytes [23]. Others have described the expression of AII receptors in human preadipocytes, claiming that AII has early, receptor-mediated effects on cell cycle progression in human preadipocytes that may contribute to their differentiation to the adipocyte phenotype [24].

Since all these products have been implicated in metabolic, neuroendocrine, immune and cardiovascular regulation [25], it is of great interest to understand the endocrine actions of products secreted by adipose tissue and their potential role in disease.

References

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