Brain circuits regulating energy homeostasis

Abizaid, Alfonso; Horváth, Tamas L.

doi:10.1016/j.regpep.2007.10.006

Cited by 139 publications

(135 citation statements)

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“…Hypothalamic nuclei have a well-established role in modulating energy homeostasis and feeding regulation; lesions of ventromedial, paraventricular, and dorsomedial nuclei or stimulation of the lateral hypothalamus (LH) produce hyperphagia, whereas lesions of the LH inhibit feeding (20). More specifically, the arcuate nucleus (Arc) lies close to the third ventricle; thus, circulating satiety and/or hunger signals, including those secreted from fat tissue, pancreas, and the gut, easily interact with this nucleus.…”

Section: Mechanistic Pathways Linking Central and Peripheral Control mentioning

confidence: 99%

“…Arc neurons produce and respond to neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocortin (POMC), and cocaine-and amphetamine-regulated transcript (CART) to influence feeding behavior and energy homeostasis (21,22). In fact, discrete activation of these Arc neurons can facilitate alterations in behavior and energy expenditure; excitation of NPY/AgRP neurons increases food intake and decreases energy expenditure, and stimulation of POMC/CART receptors inhibits food intake and increases energy expenditure (20,23). Thus, some peripherally secreted substrates modulate feeding and energy expenditure via direct action on these cells within the Arc.…”

Section: Mechanistic Pathways Linking Central and Peripheral Control mentioning

confidence: 99%

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Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism

Hanlon

Cauter

2011

Proc. Natl. Acad. Sci. U.S.A.

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Rates of obesity have been steadily increasing, along with disorders commonly associated with obesity, such as cardiovascular disease and type II diabetes. Simultaneously, average sleep times have progressively decreased. Recently, evidence from both laboratory and epidemiologic studies has suggested that insufficient sleep may stimulate overeating and thus play a role in the current epidemic of obesity and diabetes. In the human sleep laboratory it is now possible to carefully control sleep behavior and study the link between sleep duration and alterations in circulating hormones involved in feeding behavior, glucose metabolism, hunger, and appetite. This article focuses on the methodologies used in experimental protocols that have examined modifications produced by sleep restriction (or extension) compared with normal sleep. The findings provide evidence that sleep restriction does indeed impair glucose metabolism and alters the cross-talk between the periphery and the brain, favoring excessive food intake. A better understanding of the adverse effects of sleep restriction on the CNS control of hunger and appetite may have important implications for public health.

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Section: Mechanistic Pathways Linking Central and Peripheral Control mentioning

confidence: 99%

Section: Mechanistic Pathways Linking Central and Peripheral Control mentioning

confidence: 99%

Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism

Hanlon

Cauter

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…26 It has been shown that neuronal damage is not only associated with structural and functional changes in the brain but also with disturbances in the immune system, energy homeostasis, autonomic stress response, and endocrine regulation. [27][28][29][30] Because it is not possible to make a causal inference based solely on our observation, this hypothesis needs to be tested in future studies investigating the long-term consequences of suboptimal CBF on major homeostatic mechanisms. Subgroup analysis on the association between cerebral blood flow and mortality…”

Section: Resultsmentioning

confidence: 99%

Total cerebral blood flow and mortality in old age

et al. 2013

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Objective: To examine the association of total cerebral blood flow (CBF) with all-cause, noncardiovascular, and cardiovascular mortality in older subjects at risk of cardiovascular disease. Methods:We included 411 subjects with a mean age of 74.5 years from the MRI substudy of the Prospective Study of Pravastatin in the Elderly at Risk. Total CBF was measured at baseline, and occurrence of death was recorded in an average follow-up period of 11.8 years. For each participant, total CBF was standardized for brain parenchymal volume. Cox regression models were used to estimate risk of all-cause, noncardiovascular, and cardiovascular mortality in relation to CBF.Results: Mortality rates among participants in low, middle, and high thirds of total CBF were 52.1, 41.5, and 28.7 per 1,000 person-years, respectively. Compared with participants in the high third of CBF, participants in the low third had 1.88-fold (95% confidence interval [CI]: 1.30-2.72) higher risk of all-cause mortality, 1.66-fold (95% CI: 1.06-2.59) higher risk of noncardiovascular mortality, and 2.50-fold (95% CI: 1.28-4.91) higher risk of cardiovascular mortality. Likewise, compared with participants in the high third of CBF, participants in the middle third had 1.44-fold (95% CI: 0.98-2.11) higher risk of all-cause mortality, 1.29-fold (95% CI: 0.82-2.04) higher risk of noncardiovascular mortality, and 1.86-fold (95% CI: 0.93-3.74) higher risk of cardiovascular mortality. These associations were independent of prevalent vascular status and risk factors. Structural and functional integrity of the brain depends on adequate supply of nutrients and oxygen through blood flow. 1 The brain is a demanding organ and consumes approximately 20% of the oxygen inspired at rest while accounting for only 2% of the body weight. 2 This high metabolic demand renders the brain tissue vulnerable to low cerebral blood flow (CBF), as several animal studies have shown that long-standing cerebral hypoperfusion leads to neuronal loss, microvascular abnormalities, and cognitive deficit. 3,4 Decreased cerebral perfusion in patients with acute traumatic brain injury and cerebrovascular accidents has been linked to adverse clinical outcomes and shorter survival. 5,6 Likewise, clinical conditions with a state of chronic reduction in CBF, such as heart failure and carotid stenosis, have been associated with an increased risk of mortality. 7,8 Despite this evidence, the independent role of CBF in the maintenance of health and survival in old age has not been thoroughly investigated.

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“…When fat stores are reduced and energy levels are low, hunger signals mediated via an increase in the gut hormone, ghrelin, and reductions in insulin, glucose, leptin and cholecystokinin (CCK) cause increases in the activity of both neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons, which in turn leads to decreased activity of the melanocortin system, leading to disinhibition of melanin-concentrating hormone (MCH) and orexin (ORX) signalling producing a marked orexigenic effect. Following a meal the reverse occurs, with high levels of glucose, insulin, CCK and reduced ghrelin levels leading to increases in pro-opiomelanocortin (POMC) and cocaine-amphetamine regulated transcript (CART) neuronal activity, in turn increasing a-melanocyte-stimulating hormone (a-MSH) release and decreasing MCH/ORX activity, leading to satiation and a termination of feeding ( Figure 2) [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Hypothalamus and The Central Control Of Feeding And Energy Hmentioning

confidence: 99%

“…Pharmacological manipulation of these targets offers another approach to regulating food intake [11].…”

Section: Direct Modulation On Neuropeptide Transmitters Within the Hymentioning

confidence: 99%

New central targets for the treatment of obesity

Sargent

Moore

2009

Brit J Clinical Pharma

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The review focuses on the central neuronal circuits involved in energy homeostasis and the opportunities these offer for pharmacological intervention to decrease feeding behaviour and reduce weight. This article is based on the presentation 'New central targets for the treatment of obesity ' (Sargent, British Pharmacological society, Clinical Section Symposium, December 2008). Central neuronal substrates controlling weight offer numerous opportunities for pharmacological intervention. These opportunities range from non-specific enhancement of monoamine signalling (triple reuptake inhibitors) to targeting specific monoamine receptor subtypes (5-HT2c and 5-HT6). The data reviewed suggest that these approaches will lead to weight loss; whether this is sufficient to produce clinically meaningful effect remains to be determined. Combination therapy targeting more than one mechanism may be a means of increasing the magnitude of the response. Preclinical studies also suggest that novel approaches targeting specific neuronal pathways within the hypothalamus, e.g. MCH1 receptor antagonism, offer an opportunity for weight reduction. However, these approaches are at an early stage and clinical studies will be needed to determine if these novel approaches lead to clinically meaningful weight loss and improvements in co-morbid conditions such as diabetes and cardiovascular disorders. The obesity problemObesity is a major global health problem and rates of obesity [body mass index (BMI) >30 kg m -2 ] have risen steadily year on year. Recent figures show an incidence of obesity of more than 1 in 4 in many parts of the USA [1]. These high rates are similar in other developed countries and the incidence of weight gain is increasing in less developed regions. Obesity is not just a cosmetic or lifestyle illness but leads to many life-threatening health complications. As the BMI increases the incidence of metabolic disorders (Type 2 diabetes), hypertension, cancer and musculoskeletal problems increases [1][2][3]. In 1999, Calle et al. reported mortality rates for all causes doubled when the BMI increased from 25 to >35 [4].The annual direct healthcare costs associated with obesity in the USA are in excess of $93 billion [5]. Particularly worrying is the fact that the incidence of obesity in children and young adults is on the increase, with some reports suggesting that up to 25% of children may be obese. The long-term health implications of these findings are far reaching and suggest that for the first time intergenerational increase in life expectancy will not occur and these children will have a shorter life span than their parents because of health complications associated with weight gain [6] (Figure 1).Obesity occurs when the balance between energy input (food intake) and energy expenditure (exercise, activity) is disrupted, i.e. more food is consumed than utilized, leading to excess fat stores being laid down. Although for some people a calorie-restricted diet and exercise can lead to a reduction in weight gain, for many peop...

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Brain circuits regulating energy homeostasis

Cited by 139 publications

References 149 publications

Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism

Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism

Total cerebral blood flow and mortality in old age

New central targets for the treatment of obesity

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