**Acknowledgements**

adipocytes [117]. These results coincide with the lowest mitochondrial activity observed in male compared to female rats [118]. These observations show that androgens inhibit thermogenic capacity in brown adipocytes and therefore the same effect could be expected

In obesity, plasmatic testosterone levels are diminished, favouring the increase in VAT mass. At the same time, low levels of testosterone induce inhibition of lipolytic metabolism and stimulate LPL expression favouring lipogenesis [119]. This altered lipolysis/lipogenesis balance contributes to an increase lipid storage in adipose cells and therefore to the development of unhealthy VAT mass expansion. Adipocyte hypertrophy is associated with higher leptin secretion into circulation. Leptin impacts on reproductive axis function by inhibiting testis testosterone production [120]. These feedback effects contribute to generate a vicious cycle

The development of a pro-inflammatory state is one of the features of unhealthy VAT mass expansion. Androgens have been described as anti-inflammatory factors. In hypogonadism, pro-inflammatory cytokines levels increase, while androgen replacement therapy decreases them [121]. Therefore, the decrease of testosterone levels associated to obesity contributes to the pro-inflammatory state observed. On the other hand, low testosterone levels in circulation would be one of the factors that activate adipogenesis, contributing to the increase of VAT adipocyte number, as observed in obese individuals. However, the effect of low androgen levels on cell hyperplasia is not strong enough to prevent adipocyte hypertrophy development, and therefore VAT depot dysfunction, main characteristics of the hypertrophic

Endocrine-metabolic alterations associated to obesity are related to WAT dysfunction, mainly VAT. However, the increase of VAT mass per se is not an unequivocal indication of VAT dysfunction, whereas the adipocyte size actually is. Therefore, the balance between hypertrophy and hyperplasia will determine the appearance of enlarged adipocytes and, consequently, the development of VAT dysfunction. There are many factors that regulate this balance in WAT expansion. In this chapter, we have addressed three of them: fructose intake, GCs and testosterone. Both, fructose intake and GCs, stimulate adipogenesis by modulating APCs competency and number, and thus terminal differentiation. However, in both cases the chronic exposure to these factors led to hypertrophic adipocytes, and therefore to an unhealthy WAT expansion. Chronic exposure to high GC levels seems to induce a resistance state in APCs that would limit their adipogenic potential, partially by a lower response to GCs stimuli due to MR expression decrease. Conversely, testosterone is an anti-adipogenic factor that favours unhealthy expansion. Obesity is associated with reduced testosterone levels, which would promote adipogenesis; however, much extensive research is needed to determine the role of androgens in APCs adipogenic potential in obesity. Finally, factors inducing adipogenesis could become a therapeutic target against

on beige adipocytes.

176 Adiposity - Epidemiology and Treatment Modalities

obese phenotype.

**3. Conclusion**

between AT dysfunction and androgen.

The authors thank CONICET (PIP 2013-0198), Fondo para la Investigación Científica y Tecnológica (FONCYT, PICT-2013-0930) and Fondation pour la Recherche en Endocrinologie, Diabetologie et Metabolisme (FPREDM 062013). The authors are grateful to Beatriz Tosti for careful manuscript edition/correction.
