Obesity, which affects up to 35% adult population of developed countries, is associated with serious comorbidities, including a high incidence of type 2 diabetes, cardiovascular disease, osteoarthritis, and an increased risk of many forms of cancer.1) To explain the etiology of obesity, many factors have been suggested. The lipostasis theory postulated that the size of the body fat depots is sensed by the central nervous system through a product of fat metabolism, which circulates in the blood and affects energy balance by influencing the hypothalamus (Kennedy et al., 1953).2) This substance was later called as leptin. Leptin, a 167-amino acid protein, is expressed primarily by adipocytes regulates food intake, which was initially identified by Zhang and colleagues in 1994.
3)Plasma leptin levels and ob gene expression are correlated with adipose tissue mass, suggesting that adipose depot size is a major regulator of leptin production. Little is known about the nutritional regulation of leptin production. Restriction and refeeding are known to regulate plasma leptin and ob gene expression in rodents and humans. The effect of high-fat diet on circulating leptin levels has been studied in several animal models. A high-fat diet also increased ob gene expression in adipose tissue of male Sprague-Dawley rats. However, this does not prevent hyperphagia and obesity, suggesting that high-fat feeding makes rodents resistant to leptin.
4)The role of glucocorticoids in pathogenesis of obesity has been investigated. High levels of glucocorticoids have been shown in many genetically obese rats. High doses of glucocorticoids have also been shown to induce leptin gene expression when injected into rats. 5,6) This was accompanied by body weight lose. Adrenalectomy and glucocorticoid antagonists have impaired obesity in ob/ob, db/db and some obese mice. Low dose glucocorticoid replacement also restored obese phenotype.7) On the basis of these reports, we also aimed to investigate how adrenalectomy (AD) affects leptin levels in rats with diet-induced obesity.
MATERIALS AND METHODSMale Sprague-Dawley rats (160-180 g body wt) were included in the study. Rats were housed in a room under conditions of controlled temperature (22Ϯ1), illumination (8 : 00 a.m.-8 : 00 p.m.), and humidity in six groups for 10 weeks. Before the experimental procedure, they were assigned to one of two dietary groups: one having a high-calorie diet (OB, nϭ19), one having a standard laboratory diet (LE, nϭ16). Each group were also subgroupped into three (Table 1). The high-calorie diet consisted of 33% powdered laboratory diet, 33% condensed milk, and sucrose by weight, with the remainder being water; this provided 68% energy as carbohydrate, 17% as protein, and 13% as fat. The standard laboratory diet provided 65% energy as carbohydrate, 24% as protein and 9% as fat.8) Body weights were monitored weekly. Eight weeks later, rats were anesthetized with thiopental (25 mg/kg), and ten animals in the obese group (OBAD) and eight animals in the lean group (LEAD)...