RESUMEN
Obesity is a world health problem that increases the risk for developing type 2 diabetes, cardiovascular disease, fatty liver, and some types of cancer. In postmenopausal women, it represents an important risk factor for the development of breast cancer (BC). Leptin is an adipokine that is secreted by fatty tissue, and high leptin levels are observed both in mouse models of obesity and in obese subjects. High levels of leptin promote the proliferation and progression of various types of cancer, including BC. This review provides a general overview of the biology of leptin, important laboratory studies, and animal and clinical models that have provided evidence for an active role of leptin in the proliferation, progression, and survival of mammary tumors. Finally, this review addresses the most recent studies on the use of leptin receptor antagonists as a novel therapeutic treatment for BC.
Asunto(s)
Neoplasias de la Mama/metabolismo , Leptina/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Modelos Animales de Enfermedad , Metabolismo Energético , Femenino , Homeostasis , Humanos , Leptina/genética , Ratones , Terapia Molecular Dirigida , Receptores de Leptina/antagonistas & inhibidores , Receptores de Leptina/química , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Factores de Riesgo , Transducción de SeñalRESUMEN
We had previously shown that neonatal leptin treatment programs thyroid function in adulthood. As both thyroid hormones (TH) and leptin increased thermogenesis, it was interesting to evaluate the effect of cold exposure on the thyroid function of neonate rats treated with leptin. Pups were divided into two groups: Lep, injected with leptin (8 mug/100 g/BW, s.c.) for the first 10 days of lactation and control (C), injected with saline. When they were 30 days old, the groups were subdivided into two subgroups: LepC and CC, which were exposed to 8 degrees C for 12 h and compared with C and Lep groups, maintained at 25 +/- 1 degrees C. Serum leptin, TH, and TSH were measured by RIA. Type I liver deiodinase (D1) and mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPD) activities were assayed by the release of (125)I from (125)I-reverse and colorimetric method respectively. Leptin receptor (OB-Rb) was evaluated by western blot. Lep group had hyperleptinemia (+22%) and lower free tri-iodothyronine (FT(3); -33%). Cold exposure increased TH both in LepC and CC groups compared with respective controls free thyroxine (FT(4):+63 and +39%; FT(3):+75 and +40%). Liver D1 activity was lower in Lep (-22%) and increased with cold exposure (LepC +51% and CC +22%). The mGPD activity was lower in Lep (-34%) and increased (fourfold) when this group is cold exposed. Hypothalamic and thyroidal OB-Rb receptors were lower in Lep group (-47 and -36% respectively) and they were restored to normal levels after cold exposure. Leptin-programmed rats had higher TH response after cold exposure. OB-Rb had a fast response to cold exposure normalizing the lower levels observed in the leptin-programmed animals and may contribute to the higher TH cold responses.