Hypothalamic Obesity: The Myth of the Ventromedial Nucleus

Gold, Richard M.

doi:10.1126/science.182.4111.488

Cited by 279 publications

(93 citation statements)

References 26 publications

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“…The hyperinsulinemia, hyperphagia, and obesity, which are consequences of the lesion, are abolished by vagotomy (44,45). However, the mechanisms by which lesions of the ventromedial hypothalamus produce this parasympathetic overactivity are unclear, and it has been proposed that the syndrome is only seen when the lesion damages the nearby ventral noradrenergic bundle (46) FIGURE 6 Schematic representation of the catecholaminergic regulation of TRH in the brain and pancreas of the rat. The experiments suggest that within the CNS, NE stimulates and DA inhibits brain TRH.…”

Section: Discussionmentioning

confidence: 99%

Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

Engler¹,

Chad²,

Jackson³

1982

J. Clin. Invest.

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AB S T R A C T These studies have been undertaken to evaluate the role of the brain noradrenergic and dopaminergic pathways in the regulation of the secretion of thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) and pancreas of the neonatal rat. When CNS stores of norepinephrine (NE) were selectively reduced by the subcutaneous administration of the dopamine-,B-hydroxylase inhibitor FLA-63, TRH concentrations were significantly reduced throughout the brain. However, when CNS stores of both NE and dopamine (DA) were depleted by the subcutaneous administration of the tyrosine hydroxylase inhibitor a-methyl-p-tyrosine (a-MT), TRH concentrations in the brain were not significantly altered.FLA-63 and a-MT did not significantly reduce pancreatic catecholamine concentrations, indicating that in the basal state, these agents predominantly deplete central catecholamine stores. Nevertheless, pancreatic TRH concentrations were markedly reduced by FLA-63, and this effect was significantly attenuated by the simultaneous intracerebroventricular (icv) administration of NE. In contrast to the effects of FLA-63, a-MT caused a significant increase in pancreatic TRH concentrations, and this effect was significantly lessened by icv DA. To determine whether the sympathetic nervous system might be one route by which these central effects are mediated, a chemical sympathectomy was induced with guanethidine. This treatment selectively reduced pancreatic concentrations of NE, and caused a marked increase in pancreatic TRH concentrations.

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Section: Discussionmentioning

confidence: 99%

Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

Engler¹,

Chad²,

Jackson³

1982

J. Clin. Invest.

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“…Moreover, data developed over ensuing years challenged components of this model. 32 However, the anatomic substrate underlying coordinated food intake control still remained obscure, as scientists in the field lacked key tools to unravel this complex hypothalamic puzzle. Nevertheless, several molecular discoveries in 1990s, especially identification of leptin 5 and melanocortin receptors [33][34][35] implicated other hypothalamic and extra-hypothalamic sites in regulating energy homeostasis.…”

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confidence: 99%

“…Paraventricular nucleus of the hypothalamus (PVH): Lesions of the PVH cause hyperphagia in the rat, indicating that a regulator of food intake resides in this nucleus. 32 Several lines of evidence nominate subsets of MC4-R-positive PVH neurons as candidates for the regulator ( Figure 5). For example, microinjections of a synthetic MC4-R agonist MT-II into the rat PVH inhibit food intake, whereas PVH administration of a synthetic MC4-R antagonist SHU9119 exerts opposite effects.…”

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confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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“…This is the result of a couple of studies that did not observe any hyperphagia or excessive weight gain after VMH lesions (9,13) and the subsequent discovery that lesions of the nearby paraventricular hypothalamic nucleus (PVN) did result in hyperphagia and obesity (e.g., 1, 29). However, this ignores the hundreds of studies that have observed hyperphagia and obesity after VMH lesions as well as subsequent studies that found major differences between the two lesion-induced obesity syndromes (e.g., 25,47,48).…”

Section: Discussionmentioning

confidence: 99%

Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway

Grundmann

Pankey

Cook

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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King. Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway. Am J Physiol Regul Integr Comp Physiol 288: R702-R707, 2005; doi:10.1152/ajpregu.00460.2004.-Previous studies have reported hyperphagia and obesity in female rats with bilateral lesions of the most posterodorsal part of the amygdala. In rats with unilateral posterodorsal amygdaloid lesions, a dense pattern of anterograde degeneration appears in the ipsilateral ventromedial hypothalamus, but not the contralateral nucleus. In the present study, female rats with unilateral ventromedial hypothalamic lesions or sham lesions were given either sham lesions or unilateral lesions of the posterodorsal amygdala (PDA) 20 days later. Unilateral lesions of the ventromedial hypothalamus resulted in hyperphagia and excessive weight gain. Subsequent amygdaloid lesions that were contralateral to the initial hypothalamic lesions resulted in hyperphagia and additional excessive weight gains, but amygdaloid lesions ipsilateral to the initial hypothalamic lesions did not. It is concluded that the effects of the two lesions on body weight are not additive and that the PDA and ventromedial hypothalamus are part of the same ipsilateral pathway regulating feeding behavior and body weight regulation. ventromedial hypothalamus; amygdala; stria terminalis; feeding behavior; body weight LESIONS OF THE MOST POSTERODORSAL part of the amygdala result in hyperphagia and excessive weight gain in rats (42). Female rats with bilateral lesions typically gain 50 -80 g in 20 days, and gains of as much as 100 g in 20 days have been observed (15,16,18,20,21). The obesity syndrome resembles that which follows lesions of the ventromedial hypothalamus (VMH) in many respects. For example, the weight gains are greater in female rats than in male rats (23), and the animals are hyperinsulinemic even when food restricted (16) and do not respond appropriately to caloric challenges (24).Excessive weight gains have been produced with small lesions limited exclusively to the posterodorsal medial amygdaloid nucleus and the intra-amygdaloid bed nucleus of the stria terminalis (42). Examination of anterograde degeneration by the amino-cupric silver method in the brains of rats given unilateral posterodorsal amygdala (PDA) lesions revealed a dense pattern of degenerating terminals in areas that have previously been shown to be involved in various aspects of feeding behavior and/or body weight regulation (17). Particularly dense staining was observed in the VMH ipsilateral to the PDA lesion, but not in the contralateral VMH. There was little to no staining in the paraventricular hypothalamic nucleus.The pattern of anterograde degeneration observed after unilateral PDA lesions suggests an ipsilateral pathway mediating feeding behavior and body weight regulation. The major pathway between the PDA and VMH is the stria terminalis (5, 6, 39), and after unilateral PDA lesions there is dense degeneration in the dorsal component and medial part of the ventral componen...

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Hypothalamic Obesity: The Myth of the Ventromedial Nucleus

Cited by 279 publications

References 26 publications

Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

Body weight is regulated by the brain: a link between feeding and emotion

Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway

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