RESUMO
Leptin is known to be associated with regulation of body weight and fat content. The effects of exogenous leptin on abdominal visceral (VS) and subcutaneous (SC) fat volume and hepatic fat-to-water ratio in leptin-deficient obese mice were investigated by (1)H magnetic resonance imaging (MRI). Chemical shift-selected fat and water (1)H MRI of control and leptin-treated mice were obtained 1 day before treatment and after 7 days of treatment (0.3 mg/kg/day). Hepatic fat-to-water ratio and VS fat volume decreased significantly with treatment, whereas SC fat volume did not change. Noninvasive measurement of fat and water content in different body regions using MRI should prove useful for evaluating new drugs for the treatment of obesity and other metabolic disorders.
Assuntos
Tecido Adiposo/anatomia & histologia , Água Corporal/química , Leptina/farmacologia , Tecido Adiposo/fisiologia , Animais , Água Corporal/fisiologia , Peso Corporal/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Infusões Subcutâneas , Gordura Intra-Abdominal/anatomia & histologia , Gordura Intra-Abdominal/química , Leptina/administração & dosagem , Leptina/deficiência , Fígado/química , Fígado/fisiologia , Imageamento por Ressonância Magnética , Camundongos , Camundongos Obesos , Gordura Subcutânea Abdominal/anatomia & histologia , Gordura Subcutânea Abdominal/químicaRESUMO
A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food intake and body weight models.
