Experimental Obesity: A Homeostatic Failure due to Defective Nutrient Stimulation of the Sympathetic Nervous System

Bray, George A.; York, D. A.; Fisler, Janis S.

doi:10.1016/s0083-6729(08)60393-3

Cited by 185 publications

(105 citation statements)

References 489 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…As can be seen in obesity, as well as in Cushing's disease, there occurs a compensatory increase in insulin which produces anabolic effects in certain tissues that accompany catabolic actions of high CORT levels in somatic muscle (175). Insulin's role is further demonstrated by the finding that removal of the adrenals, which reverses the obesity, normalizes the insulin levels and insulin sensitivity in these animals, while CORT produces the opposite (137,143). This normalization of insulin function in ADX animals may, then, permit insulin receptors in the brain to perform their function of inhibiting food intake and body weight gain, in proportion to the body's fuel stores (173,177).…”

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 98%

“…Removal of the adrenals, which eliminates essentially all CORT from the blood, results in a decline in 24-h caloric intake of approximately 20-30% and a decrease in body weight gain (143). In rats fed pure macronutrient diets, the consumption of carbohydrate and fat is most dramatically and consistently reduced, although a predominant effect on fat intake may occur in obese rats with a strong preference for this nutrient (144) and variable changes in protein intake can be seen (145,146).…”

Section: Effects Of Adx and Cort Replacement On Nutrient Intake And Mmentioning

confidence: 99%

“…Within the hypothalamus, the arcuate nucleus (ARC), while being unresponsive to the feeding effects of steroid implants (183), may be particularly important in mediating CORT's interaction with neuropeptide systems that govern circadian rhythms of food intake and particularly carbohydrate ingestion (see below). Additional areas involved in modulating ingestion and metabolism include the ventromedial (VMH ) and lateral (LH) hypothalamic regions (24,137,143,184). These sites are active in controlling circulating levels of insulin and glucose and, glucose, or stimulate respiratory quotient indicating an enhancement in carbohydrate utilization (28,203,204).…”

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 99%

“…Under normal conditions, body weight can be tightly regulated, as indicated by the ability of animals and humans to maintain constant body weight over long periods of time. A role for the adrenal steroids in this process is indicated by the finding that, in normal-weight animals, ADX suppresses body weight gain within 2-3 days after surgery, leading to a permanent decrease in body weight, and this decline in body weight can be readily reversed by chronic administration of the steroids (137,143,144,149,153,(247)(248)(249).…”

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 99%

“…Other evidence indicates that both the type I and type I1 receptor systems are involved in the maintenance of the obesity (137,143,149,259,260). An increase in density of type I and type I1 receptors has been reported in the brains of obese animals (260).…”

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 99%

See 4 more Smart Citations

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

195

127

View full text Add to dashboard Cite

The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

show abstract

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 98%

Section: Effects Of Adx and Cort Replacement On Nutrient Intake And Mmentioning

confidence: 99%

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 99%

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 99%

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 99%

See 3 more Smart Citations

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

195

127

View full text Add to dashboard Cite

show abstract

Animal Models of Obesity

York

2003

International Textbook of Diabetes Mellitus

View full text Add to dashboard Cite

Animal models have played an important role in advancing our understanding of the causes and consequences of obesity. The spontaneous single gene mutations led to the discovery of leptin and the melanocortin signaling pathways and were important to the understanding of hypothalamic systems that control energy balance. The use of transgenic and gene targeting technologies has opened a new era of investigation, identifying new genes that regulate the development or prevention of obesity and providing the tools for proof of function of genes. These studies have shown that a wide range of genes expressed primarily in the central nervous system or in adipose tissue are potential targets for the treatment of obesity.

show abstract

Overview of Rodent Models for Obesity Research

Tschöp

Heiman

2001

CP Neuroscience

View full text Add to dashboard Cite

Animal obesity models differ widely in type and extent of obesity. They are either based on environmental factors (e.g., high-fat diet-induced obesity), spontaneous mutants (i.e., ob/ob mice), genetically engineered animals (e.g., mice with melanocortin receptor subtype-4 gene disruption (knock-out), or mechanical intervention (e.g., chemical lesion of the ventromedial hypothalamus). This unit reviews available rodent models to study obesity and attempts to highlight the greatest utility for each model.

show abstract

Experimental Obesity: A Homeostatic Failure due to Defective Nutrient Stimulation of the Sympathetic Nervous System

Cited by 185 publications

References 489 publications

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Animal Models of Obesity

Overview of Rodent Models for Obesity Research

Contact Info

Product

Resources

About