Leptin Stimulates Neuropeptide Y and Cocaine Amphetamine-Regulated Transcript Coexpressing Neuronal Activity in the Dorsomedial Hypothalamus in Diet-Induced Obese Mice

Lee, Shin J.; Verma, Saurabh; Simonds, Stephanie E.; Kirigiti, Melissa A.; Kievit, Paul; Lindsley, Sarah R.; Loche, Alberto; Smith, M. Susan; Cowley, Michael A.; Grove, Kevin L.

doi:10.1523/jneurosci.0837-13.2013

Cited by 68 publications

(50 citation statements)

References 58 publications

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“…Human and animal studies suggest that adiposity-induced leptin increase and subsequent leptin resistance would affect these transmitters, causing or worsening asthma symptoms. This relates both to orexigenic neuropeptides such as neuropeptide Y (114)(115)(116)(117)(118)(119)(120) , endocannabinoids (121,122) , endogenous opioids (123)(124)(125)(126) ; and anorexigenic neuropeptides such as tachykinins and its most studied members substance P (127)(128)(129)(130)(131)(132) , α-melanocyte-stimulating hormone (133)(134)(135) , corticotropin-releasing factor (136)(137)(138)(139)(140)(141) and serotonin (142)(143)(144)(145)(146)(147)(148)(149)(150) . Altogether, it suggests that these peptides can modulate asthmatic inflammation among obese patients.…”

Section: Possible Linksmentioning

confidence: 99%

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

2016

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Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesityinduced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

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Section: Possible Linksmentioning

confidence: 99%

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

2016

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“…Besides, NPY is expressed in the DMH, and its overexpression is able to induce hyperphagia and obesity [65] , while DMH neurons that lack NPY promote thermogenesis and prevent diet-induced obesity (DIO) [66] . In this sense, leptin's action on the DMH increases the sympathetic tone to BAT, probably by activating NPY in the DMH and contributing to the hypothalamic regulation of thermogenesis [67,68] . Moreover, CART is coexpressed with NPY in chronic obesity; its function seems related to hypothalamic adaptations to increased adiposity and hyperleptinaemia [68] .…”

Section: Hypothalamic Regulation Of Energy Balancementioning

confidence: 99%

“…In this sense, leptin's action on the DMH increases the sympathetic tone to BAT, probably by activating NPY in the DMH and contributing to the hypothalamic regulation of thermogenesis [67,68] . Moreover, CART is coexpressed with NPY in chronic obesity; its function seems related to hypothalamic adaptations to increased adiposity and hyperleptinaemia [68] .…”

Section: Hypothalamic Regulation Of Energy Balancementioning

confidence: 99%

Hypothalamic Lipids: Key Regulators of Whole Body Energy Balance

et al. 2016

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Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase and AMP-activated protein kinase, impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues not suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases such as insulin resistance, cardiomyopathy, atherosclerosis, and steatohepatitis. Current data have reported that, similar to what is observed in peripheral tissues, complex lipids such as ceramides and sphingolipids act as lipotoxic species at the hypothalamic level to impact metabolism. Here, we will review what is currently known about hypothalamic lipid metabolism and the modulation of energy homeostasis.

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“…43 Interestingly, NPY expression in the DMH is delayed in diet-induced obesity and does not peak until there is a rapid weight gain. 44 As we have examined changes occurring in the first weeks of an HFD, it is possible that the NPY neurons in the DMH may not yet be activated. In support of our findings, it has been shown that in the obese Zucker rat, the presynaptic effects of NPY are attenuated compared with lean littermates.…”

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confidence: 99%

Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity

et al. 2016

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O besity, a state of excessive adipose tissue accumulation, has reached epidemic proportions worldwide, and this increasing global prevalence constitutes a major public health challenge. Obesity is one of the main causes of hypertension. Both human and animal studies present a strong link between bodyweight gain and greater blood pressure.1 Importantly, obesity-related hypertension is caused by an interaction of humoral and neural mechanisms, 2,3 and inappropriate increases in sympathetic tone are thought to be the major cause of the hypertension. [4][5][6] Indeed, clinical data show that when compared with normal subjects, noradrenaline spillover rates are greater among obese individuals. 7 Furthermore, in studies using dog and rat models of obesity, bilateral renal denervation attenuated the hypertension 8,9 and combined α-and β-adrenergic blockade has been shown to prevent high fat diet (HFD)-induced hypertension in conscious rabbits. 10 Although the close link between the obesity and the prevalence of hypertension has been well established, a key focus in the field remains the identification of mechanisms underlying sympathetic overdrive in obesity.The adipokine leptin is a 16-kDa peptide that is secreted primarily by white adipose tissue and found in serum in direct proportion to adiposity. In addition to the weight loss effect, leptin has also been shown to activate sympathetic nerve activity (SNA) in the kidneys, hindlimbs, and adrenal glands, which suggested its potential role in the increased SNA in obesityrelated hypertension. 4 Plasma leptin levels correlate strongly with blood pressure and renal SNA (RSNA) while central administration of leptin increases mean arterial pressure (MAP) in both rats and rabbits via stimulation of the sympathetic nervous system. 3,11 Hence, the effect of increased circulating leptin because of high adiposity is considered a primary link between obesity and increased SNA. 3,12 The central effects of leptin are thought to be mediated primarily through the arcuate nucleus of the hypothalamus from which peripheral signals are relayed downstream to other hypothalamic nuclei via a network of second-order neurons.13 Pro-opiomelanocortin and neuropeptide Y (NPY) neurons in the arcuate nucleus form the main population of neurons expressing the leptin receptor, which propagate leptin signals throughout the hypothalamus Abstract-High fat diet (HFD)-induced hypertension in rabbits is neurogenic and caused by the central action of leptin, which is thought to be dependent on activation of α-melanocortin-stimulating hormone (α-MSH) and neuropeptide Y-positive neurons projecting to the dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). However, leptin may act directly in these nuclei. Here, we assessed the contribution of leptin, α-MSH, and neuropeptide Y signaling in the DMH and VMH to diet-induced hypertension. Male New Zealand white rabbits were instrumented with a cannula for drug injections into the DMH or VMH and a renal sympathetic nerve activity (RSNA) electrode....

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Leptin Stimulates Neuropeptide Y and Cocaine Amphetamine-Regulated Transcript Coexpressing Neuronal Activity in the Dorsomedial Hypothalamus in Diet-Induced Obese Mice

Cited by 68 publications

References 58 publications

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

Hypothalamic Lipids: Key Regulators of Whole Body Energy Balance

Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity

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