Obesidad monogénica / Monogenic obesity

La obesidad infantil es un problema creciente de salud, asociado con una significativa morbilidad física y psicológica a edades tempranas. La obesidad es una enfermedad multifactorial, causada en la mayoría de los casos por la interacción de determinados polimorfismos genéticos con el medio ambiente. Solo en un 5 % resulta de mutaciones en genes específicos, originando en algunos casos síndromes mendelianos de muy escasa incidencia en la población que se clasifican como obesidades monogenicas. La mayoría de estos genes están implicados en la regulación del hambre-saciedad en el sistema nervioso central, en el cual el eje de leptina-melanocortina desempeña un rol fundamental. Se presentan clínicamente como formas de obesidad de inicio precoz, severas, que se asocian con trastornos de la conducta alimentaria y alteraciones endocrinológicas. La mutación en el gen del receptor melanocortina-4 (MC4R) es la causa más común de obesidad monogénica grave de aparición temprana. El objetivo de esta revisión es realizar una actualización sobre las obesidades de inicio precoz de causa monogénicas, su etiopatogenia, sus principales características clínicas y su abordaje terapéutico. El manejo de estos pacientes aún es un reto, ya que el tratamiento específico solo se encuentra disponible en un solo tipo de obesidad monogénica. Para el resto de los tipos se encuentran en investigación nuevas moléculas que actúan sobre la vía leptina-melanocortina

Childhood obesity is a growing health problem associated with significant physical and psychological morbidity at an early age. Obesity is a multifactorial disease in the majority of cases caused by an interaction of certain genetic polymorphisms and the environment. In only 5% of the patients it is related to specific gene mutations in some cases resulting in very rare Mendelian syndromes classified as monogenic obesity. The majority of these genes are involved in the hunger-satiety regulation in the central nervous system, in which the leptin-melanocortin axis plays a fundamental role. Clinically, these forms of obesity present at an early age, are severe, and are associated with eating disorders and endocrine alterations. A mutation in the melanocortine-4 receptor (MC4R) gene is the most common cause of early-onset severe monogenic obesity. The aim of this review was to provide an update of the different forms of early-onset monogenic obesity, focusing on the etiopathogenicity, main clinical features, and therapeutic approach. The management of these patients is still a challenge as specific treatment is only available for one type of monogenic obesity. For the remaining types new molecules that act on the leptin-melanocortin pathway are currently being investigated

Expression of melanocortin receptors mRNA, and direct effects of ACTH on steroid secretion in the bovine ovary.

Melanocortin receptors (MCRs) are involved in physiological responses to ACTH, as well as to α-, ß- and γ-melanocyte-stimulating hormone (α-, ß- and γ-MSH). Their expression has previously been analyzed in various bovine tissues; however, there are apparently no reports regarding their localization in the ovaries. In the present study, the expression of MCR mRNA in various bovine ovarian structures was characterized with reverse transcription polymerase chain reaction (RT-PCR). Furthermore, whether ACTH affected follicular components by affecting steroid secretion in fragments of ovarian follicular wall of medium and large antral follicles cultured in serum free medium with 1, 10, and 100 nM ACTH, was also determined. Melanocortin receptors mRNA was localized in the theca cells of various follicular stages, whereas only MC3R mRNA was weakly evident in granulosa cells. Melanocortin receptors 1, 2, and 3 mRNA were present in the CL, whereas in stroma, only MC2R mRNA was expressed. There were significant increases in estradiol and cortisol concentrations in response to ACTH in medium follicles, as well as increased concentrations of testosterone and cortisol in large follicles. These results confirmed earlier reports in other species, and demonstrated that MCRs were present in bovine ovaries. Since ACTH induced steroid secretion from the ovary in vitro, we inferred that melanocortin peptides could be involved in regulatory mechanisms related to ovarian functions, e.g. ovulation, steroidogenesis, and luteal function.