Studies of different female rat models of hypothalamic obesity

Abstract

Hypothalamic obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions and is associated with hyperinsulinemia and hyperleptinemia. The purpose of this study was to create a rodent model that mimics metabolic changes in HO for use in therapeutic testing. Female SpragueDawley rats were used to test the individual and combined effects of two types of medial hypothalamic lesions: arcuate nucleus (ARC) lesions by injection of monosodium glutamate at neonatal age, and ventromedial nucleus (VMN) lesions by passing an anodal current through an electrode placed in the VMN at age 80 days. Adiposity in ARC-lesioned animals was associated with decreased food intake and stunted growth, while VMN lesions were associated with hyperphagia but not reduced growth. The greatest weight gain (weight at age 200 days 712 ± 65 vs. 451 ± 19 g in controls), hyperphagia (food intake 10 days following surgery 33 ± 0.8 vs. 18.5 ± 0.7 g/day in sham-treated rats), hyperinsulinemia and hyperleptinemia occurred in rats that received both ARC and VMN lesions. Thus, the combined medial hypothalamic lesions result in an obesity phenotype similar to that of patients that suffer from HO and are consequently more suitable for testing potential therapeutics for this disorder than lesions of single hypothalamic nuclei.

Efeito da redução de ninhada sobre as respostas autonômicas e metabólicas de ratos Wistar

“…O hipotálamo é uma das regiões centrais mais completas da citoarquitetura neural, ficando, durante o período lactacional, susceptível a influências metabólicas que podem alterar sua homeostase 28,29 . Dessa forma, caracteriza-se como uma importante janela de desenvolvimento metabólico.…”

“…O controle da ingestão de nutrientes e o equilíbrio homeostático dependem de sinais periféricos que atuam diretamente sobre SNC, desempenhando a região hipotalâmica um papel chave na integração de sinais periféricos e controle da homeostase energética 29 . Circuitos neuronais desse sistema, principalmente aqueles localizados no hipotálamo, recebem e integram sinais metabólicos, endó-crinos e neurais, coordenando respostas, através do metabolismo, com objetivo de controle do peso corporal 38 .…”

Glucagon-Like Peptide-1 Agonist Exendin-4 Leads to Reduction of Weight and Caloric Intake in a Rat Model of Hypothalamic Obesity

“…We recently developed a novel combined medial hypothalamic lesion (CMHL) model that utilizes electrolytic lesions in the ARC, VMG, and DMN of the medial hypothalamus to model the sequelae commonly observed in HO secondary following the resection and/or radiotherapy of CP [22]. We found similar results when combining electrolytic lesions of the VMN with chemical lesions of the ARC [17]. The CMHL model best mimics the complex metabolic abnormalities observed in CP patients with HO including rapid weight gain, hyperphagia, hyperinsulinemia, and hyperleptinemia.…”

“…Despite these findings, weight loss through caloric restriction and exercise has been largely unsuccessful [12,13]. Pharmacological treatment of HO and hyperphagia have shown success in a few case reports and clinical trials [12,14,15,16,17], although weaker reductions were observed compared to uncomplicated obesity [15]. …”

Swim training and the genetic expression of adipokines in monosodium glutamate-treated obese rats

“…Rats treated with MSG in the first days after birth deve lop obesity in adult life and present insulin resistance, glucose intolerance, dyslipidemia and cardiovascular dysfunction, which are typical symptoms of metabolic syndrome carriers (3). Similar to obese subjects, MSG obese rats present lowgrade chronic inflammation, in particular on adipocyte tissue.…”