Evidence for a Central Mechanism of Obesity in the Zucker Fatty Rat (fa/fa)

Martin, Roy J.; Harris, Ruth B. S.; Jones, D. D.

doi:10.3181/00379727-183-42380

Cited by 27 publications

(13 citation statements)

References 42 publications

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“…It is postulated that this effect is mediated via disinhibition of sympathetically mediated thermogenesis (14). On the other hand, fatty (fa/ fa) rats with a mutation in the gene encoding the long form of the leptin receptor that disrupts intracellular signaling events (11,24,25,44,55,56) develop profound obesity that is linked to impaired sympathetic regulation of peripheral metabolism (33,34,37).Despite the straightforward results obtained in the animal models just cited, questions remain regarding the role that sympathetic activation plays in regulating body weight. Decreased sympathetic activity is associated with weight gain in rodent models of obesity, but muscle sympathetic nerve activity measured by direct recordings obtained from the peroneal nerve is increased in obese human subjects (49, 50).…”

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confidence: 84%

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confidence: 99%

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Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

Dobbins¹,

Szczepaniak²,

Zhang³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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To assess the importance of the sympathetic nervous system in regulating body weight during prolonged leptin infusion, we evaluated food intake, body weight, and physical activity in conscious, unrestrained rats. Initial studies illustrated that prolonged intracerebroventricular (ICV) infusion of leptin enhanced substrate oxidation so that adipose tissue lipid stores were completely ablated, and muscle triglyceride and liver glycogen stores were depleted. After neonatal chemical sympathectomy, changes in weight and food intake were compared in groups of sympathectomized (SYM) and control (CON) adult animals during ICV infusion of leptin. CON animals lost 60 Ϯ 9 g over 10 days vs. 25 Ϯ 3 g in the SYM animals when food intake was matched between the two groups. Greater weight loss despite similar energy intake points to an important role of the sympathetic nervous system in stimulating energy expenditure during ICV leptin infusion by increasing the resting metabolic rate, since no differences in physical activity were observed between CON and SYM groups. In conclusion, activation of the SNS by leptin increases energy expenditure by augmenting the resting metabolic rate. lipid oxidation; sympathetic nervous system; intracerebroventricular ADMINISTRATION OF LEPTIN in normal rodents activates the ventromedial hypothalamus, resulting in both anorexia and increased sympathetic stimulation of peripheral tissues (7,19,42). Seminal studies indicate that leptin infusion enhances daily energy expenditure in food-restricted animals by preventing circadian decreases in resting energy expenditure that are normally observed during the first few hours of the light cycle (14,22,39,51,52). It is postulated that this effect is mediated via disinhibition of sympathetically mediated thermogenesis (14). On the other hand, fatty (fa/ fa) rats with a mutation in the gene encoding the long form of the leptin receptor that disrupts intracellular signaling events (11,24,25,44,55,56) develop profound obesity that is linked to impaired sympathetic regulation of peripheral metabolism (33,34,37).Despite the straightforward results obtained in the animal models just cited, questions remain regarding the role that sympathetic activation plays in regulating body weight. Decreased sympathetic activity is associated with weight gain in rodent models of obesity, but muscle sympathetic nerve activity measured by direct recordings obtained from the peroneal nerve is increased in obese human subjects (49, 50). Furthermore, peripheral sympathetic nerve terminals have been destroyed in rats by triggering an immune-mediated response with repeated injections of guanethidine or 6-hydroxydopamine (27)(28)(29). Surprisingly, chemically sympathectomized rats do not gain more weight than untreated littermates, even when challenged with a high-fat diet (27,29,35,45). Given the complex nature of the multiple processes controlling energy balance, it is likely that additional mechanisms are triggered that compensate for the loss of peripheral sympathetic nerves. If...

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confidence: 84%

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confidence: 99%

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

Dobbins¹,

Szczepaniak²,

Zhang³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…Training delays the onset of fatigue, which in any case often appears faster in the exercising obese than in the lean. The genetically obese Zucker fa/fa rat accumulates inordinate amounts of fat, 14 because of a defect in its thermogenic system 14,15 and the need to maintain its body temperature at the expense of residual metabolism, 16 and its glucose and lipid metabolism is deeply altered because of high resistance to glucose. 17 In the present study we have determined the fate of muscle glycogen, hexose-phosphate pool and blood-borne glucose during a short, intense bout of exercise in the obese rat compared with the lean, in order to determine whether the difference in glucose disposal has a direct bearing in the limited exercise capacity of obese rats.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate handling in exercising muscle of obese Zucker rats

et al. 1997

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OBJECTIVE: To determine the differential substrate utilization of substrates by exercising muscle and in the fatigued state in lean and obese rats. DESIGN: The rats were treadmill-exercised until fatigued, when their oxygen consumption increased by 1.856 factor. Blood and hind leg tissue (muscle and skin) were sampled at intervals during exercise and recovery. SUBJECTS: Lean and obese adult Zucker female rats. MEASUREMENTS: Three series of rats were used to determine hind-leg glucose, lactate and oxygen arterio-venous balances, blood¯ow and muscle levels of glucose, hexose-P, glycogen, lactate and skin lactate. The rates of glycosyl unit¯ow during exercise and recovery were then calculated. RESULTS: In obese rats, exercising muscle showed higher glucose uptake, increased glycogen mobilization and lower lactate production than in the lean. In the obese rats' muscle, there were more glycosyl units available for oxidative metabolism. Excess glycosyl (or 3C) units were used probably for lipid synthesis. Lean rats managed their glycosyl units more ef®ciently, stretching the available glycogen, thus prolonging the exercise. During recovery, obese rats massively synthesized glycogen and lowered lactate ef¯ux, which left only a few glycosyl units to oxidative metabolism; probably the rest of oxidative energy was derived from lipids. CONCLUSION: In lean rats glucose is the main source of muscle energy during exercise and recovery, whereas obese rats use glucose during exercise, and probably synthesize lipid during exercise. Obese rats rely more on lipids for energy during recovery.

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“…Symptoms of experimental and genetic obesity, e.g., adiposity, hyperinsulinemia, and hyperphagia, are accompanied by profound changes in autonomic functioning (6,19,25,26). Several authors suggest a causal relationship between obesity and altered autonomic functioning, in which, for example, hyperinsulinemia can be explained by increased activation of the 7248 OBESITY RESEARCH Vol.…”

Section: Obesitymentioning

confidence: 99%

Energy Homeostasis, Autonomic Activity and Obesity

Scheurink¹,

Balkan²,

Nyakas³

et al. 1995

Obesity Research

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Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats. Particular emphasis is given to autonomic functioning and dysfunctioning in relation to the processes that are involved in the regulation of peripheral energy substrate homeostasis. It is concluded that alterations in autonomic regulation in obesity are determined by causal factors such as overeating, genetic make-up, age andfor the duration of obesity. 1995;3(S~ppl5):721S-727S.

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Evidence for a Central Mechanism of Obesity in the Zucker Fatty Rat (fa/fa)

Cited by 27 publications

References 42 publications

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

Carbohydrate handling in exercising muscle of obese Zucker rats

Energy Homeostasis, Autonomic Activity and Obesity

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