RESUMEN: Según la Organización Mundial de la Salud las enfermedades crónicas degenerativas son enfermedades de larga duración y de progresión lenta. Entre ellas se encuentran las enfermedades cardiovasculares (ECV), el cáncer, las enfermedades respiratorias y la Diabetes Mellitus tipo 2. En México, la muerte prematura por ECV en el 2011 se estimó que fue de 25,941en hombres y 16,190 en mujeres de 30 a 69 años de edad, las cuales la hipercolesterolemia se considera como el mayor riesgo asociado (OPS / OMS). La administración de las variantes de leptina, han mostrado tener efectos diversos sobre la regulación del balance energético, la homeostasis de glucosa y el metabolismo de lípidos. En el presente trabajo, se observó los efectos sobre el peso corporal, las concentraciones de colesterol total y triglicéridos en suero e hígado, así como el efecto de la expresión relativa de genes involucrados en el metabolismo de lípidos (Cd36, Lpl, Fas, Scd1 y ApoaIV) en tejido hepático, por la administración de las variantes de leptina W100E y BCH2, en dos diferentes modelos murinos: C57BL/6J (sano) y C57BL/6J KO apoE (hipercolesterolémico). El tratamiento tuvo una duración de 6 días con una dosis diaria de 4 mg / Kg peso de ratón. El efecto más importante en este trabajo resultó ser que el uso de la variante de leptina BCH2 mostró un efecto benéfico al disminuir la concentración de colesterol total en ratones KO apoE (hipercolesterolemia principalmente colesterol LDL), disminución de peso corporal y además mostró una reducción en la expresión de genes involucrados en el metabolismo de lípidos y en la síntesis de colesterol (Cd36, Scd1, Fas, ApoAIV, y Lpl). Se propone, de acuerdo a la revisión bibliográfica, que el posible mecanismo por el cual las variantes de leptina regulan la expresión de genes, es gracias a la activación de AMPK y PPAR, así como la inhibición de la 9 activación de SREBP1c, dando como resultados los diversos efectos benéficos sobre la concentración de colesterol en suero, el peso corporal y la disminución de la expresión de genes relacionados con la lipogénesis. According to the World Health Organization, the chronic degenerative diseases are long-term and slowly progressive diseases. These include cardiovascular disease (CVD), cancer, respiratory diseases and type 2 diabetes mellitus. In Mexico, premature death due to CVD in 2011 was estimated to be 25,941 in men and 16,190 in women between 30 and 69 years of age, with hypercholesterolemia being considered as the greatest associated risk (PAHO / WHO). The administration of leptin variants have been shown to have diverse effects on the regulation of energy balance, glucose homeostasis and lipid metabolism. In the present study, the effects on body weight, total cholesterol and triglyceride concentrations in serum and liver, as well as the effect of relative expression of genes involved in lipid metabolism (Cd36, Lpl, Fas, Scd1 And ApoAIV) in hepatic tissue, through the administration of leptin variants W100E and BCH2, in two different murine models: C57BL / 6J (healthy) and C57BL / 6J KO apoE (hypercholesterolemic). The treatment had a duration of 6 days with a daily dose of 4 mg / kg mouse weight. The most important effect in this study was that the use of the leptin BCH2 variant showed a beneficial effect in decreasing the total cholesterol concentration in KO apoE mice (hypercholesterolemia, mainly LDL cholesterol), decrease in body weight and also showed a reduction in the expression of genes involved in lipid metabolism and in cholesterol synthesis (Cd36, Scd1, Fas, ApoAIV, and Lpl). It is proposed, according to the literature review, that the possible mechanism by which leptin variants regulate gene expression is thanks to the activation of AMPK and PPAR, as well as the inhibition of the activation of SREBP1c, resulting in the various beneficial effects on serum cholesterol concentration, body weight and decreased expression of genes related to lipogenesis.
ABSTRACT: According to the World Health Organization, the chronic degenerative diseases are long-term and slowly progressive diseases. These include cardiovascular disease (CVD), cancer, respiratory diseases and type 2 diabetes mellitus. In Mexico, premature death due to CVD in 2011 was estimated to be 25,941 in men and 16,190 in women between 30 and 69 years of age, with hypercholesterolemia being considered as the greatest associated risk (PAHO / WHO). The administration of leptin variants have been shown to have diverse effects on the regulation of energy balance, glucose homeostasis and lipid metabolism. In the present study, the effects on body weight, total cholesterol and triglyceride concentrations in serum and liver, as well as the effect of relative expression of genes involved in lipid metabolism (Cd36, Lpl, Fas, Scd1 And ApoAIV) in hepatic tissue, through the administration of leptin variants W100E and BCH2, in two different murine models: C57BL / 6J (healthy) and C57BL / 6J KO apoE (hypercholesterolemic). The treatment had a duration of 6 days with a daily dose of 4 mg / kg mouse weight. The most important effect in this study was that the use of the leptin BCH2 variant showed a beneficial effect in decreasing the total cholesterol concentration in KO apoE mice (hypercholesterolemia, mainly LDL cholesterol), decrease in body weight and also showed a reduction in the expression of genes involved in lipid metabolism and in cholesterol synthesis (Cd36, Scd1, Fas, ApoAIV, and Lpl). It is proposed, according to the literature review, that the possible mechanism by which leptin variants regulate gene expression is thanks to the activation of AMPK and PPAR, as well as the inhibition of the activation of SREBP1c, resulting in the various beneficial effects on serum cholesterol concentration, body weight and decreased expression of genes related to lipogenesis.
