Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

Lopaschuk, Gary D.; Ussher, John R.; Jaswal, Jagdip S.

doi:10.1124/pr.109.002428

Cited by 62 publications

(66 citation statements)

References 403 publications

(468 reference statements)

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“…Acute administration of obestatin in the high doses inhibited food consumption both in mice, and in lean and fatty Zucker rats (Lagaud et al, 2007). On the other hand, in numerous comprehensive studies performed on rodents, no significant effect of peripherally or centrally administered obestatin was observed on food intake, energy expenditure or body weight with either acute or chronic treatment (for review see Lopaschuk et al, 2010).…”

Section: Obestatinmentioning

confidence: 99%

“…NPY activity is reduced under feeding conditions, whereas the malnutrition stimulates its activity (Schneeberger et al, 2014). Moreover, intracerebroventricular (ICV) administration of NPY or its direct administration into specific hypothalamic nuclei increases food intake, whereas the administration of receptor selective antagonists (Y1 and Y5 antagonists) or antisense oligonucleotides (Y5 receptor) reduces or inhibits food intake (Lopaschuk et al, 2010).…”

Section: Appetite Regulating Networkmentioning

confidence: 99%

“…Moreover, ICV infusion of CART results in the appetite reduction, while antibodies against CART reverse this effect (Schneeberger et al, 2014). It has been demonstrated, that polymorphisms of the gene, as well as alterations in CART protein level, are associated with human obesity (Lopaschuk et al, 2010).…”

Section: Appetite Regulating Networkmentioning

confidence: 99%

“…NPY is one of the most abundant neuropeptides synthetized in different brain areas but the neurons involved in the appetite regulation are synthetized mainly in the ARC (Lopaschuk et al, 2010). The effects of NPY on energy balance regulation are mediated by postsynaptic Y1 and Y5 receptors, which belong to the class of G protein-coupled receptor subtypes (Nguyen et al, 2012).…”

Section: Appetite Regulating Networkmentioning

confidence: 99%

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Hypothalamo-gastrointestinal axis – role in food intake regulation

Wójcik-Gładysz¹,

Szlis²

2016

J. Anim. Feed Sci.

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Section: Obestatinmentioning

confidence: 99%

Section: Appetite Regulating Networkmentioning

confidence: 99%

Section: Appetite Regulating Networkmentioning

confidence: 99%

Section: Appetite Regulating Networkmentioning

confidence: 99%

See 2 more Smart Citations

Hypothalamo-gastrointestinal axis – role in food intake regulation

Wójcik-Gładysz¹,

Szlis²

2016

J. Anim. Feed Sci.

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“…It was found that ghrelin acts to promote appetite in two ways-directly, by depolarizing the orexigenic NPY/AgRP neurons, and indirectly, by increasing the tonic inhibition exerted by the NPY/AgRP neurons over the anorexigenic POMC/CART neurons. Both of these ultimately enhance appetite [4,17,18]. The ability of ghrelin to increase food intake and body weight is mediated through the stimulation of NPY production in the hypothalamic ARC, where it antagonizes the inhibitory effect on NPY secretion displayed by leptin and insulin [19].…”

mentioning

confidence: 99%

Appetite Regulatory Peptides and Insulin Resistance

Orbetzova¹

2012

Insulin Resistance

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In addition to leptin and insulin, receptors for ghrelin are also located on arcuate AgRP/NPY neurons, which are activated by central ghrelin administration. Furthermore, peripheral ghrelin administration activates neurons in the ARC and AgRP and NPY have been demonstrated to be requisite mediators of the hyperphagia induced by systemic ghrelin [11]. So, meal-generated satiety signals from the GI tract do interact with longer-term adiposity signals, such as insulin and leptin in energy balance [8].NPY is one of the most abundant peptides of the hypothalamus and one of the most potent orexigenic factors. The majority of neurons expressing NPY in the hypothalamus are found within the ARC and most co-express AgRP [14]. Synthesis and release of NPY are both regulated by leptin binding to its hypothalamic receptor. NPY links afferents reflecting the nutritional status of the organism from endocrine, gastrointestinal, and central and peripheral nervous systems to effectors of energy intake and expenditure [15]. NPY stimulates appetite inducing hyperphagia, increase of fat depots, decrease of thermogenesis, and suppression of sympathetic activity. NPY is known to be involved in other physiological functions, such as cardiovascular regulation, affective disorder, memory retention, neuroendocrine control. When leptin levels increase after food intake, the latter binds to its receptors in the hypothalamus which leads to discontinuation of NPY secretion [5,16]. The decrease of NPY concentration in obesity probably plays a role of a counterregulatory factor intended to prevent further weight gain. Thus, NPY becomes one of the main regulators of food intake, body weight and energy expenditure.Ghrelin is a fast-acting hormone, seemingly playing a role in meal initiation. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue-receptor (GHS-R) in the pituitary gland, thus fulfilling the criteria of a brain- gut peptide [5,6]. Although the majority of ghrelin is produced peripherally, there are ghrelin immunoreactive neurons within the hypothalamus that have terminals on hypothalamic NPY/AgRP, POMC and corticotropin releasing hormone (CRH) neurons [17], as well as orexin fibres in the LHA [18]. It was found that ghrelin acts to promote appetite in two ways-directly, by depolarizing the orexigenic NPY/AgRP neurons, and indirectly, by increasing the tonic inhibition exerted by the NPY/AgRP neurons over the anorexigenic POMC/CART neurons. Both of these ultimately enhance appetite [4,17,18]. The ability of ghrelin to increase food intake and body weight is mediated through the stimulation of NPY production in the hypothalamic ARC, where it antagonizes the inhibitory effect on NPY secretion displayed by leptin and insulin [19].The purpose of this chapter is to provide background information on the relationship between the main appetite regulatory peptides NPY and ghrelin, and insulin resistance. The role of NPY and ghrelin in food intake and body weight control in humans, and their ...

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Lipids, Brain, and Mental Health

Hussain

Rasul

Anwar

et al. 2020

Bailey's Industrial Oil and Fat Products

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Lipids in nervous system are of particular interest because of the high concentration of lipids in brain, second only to adipose tissue, of which a major part is found in myelin. These lipids are involved in the structure of cell membranes in the brain and display a variety of biological functions to maintain vital cellular processes at various levels: work as energy source, serve as signaling molecules, and withstand structural integrity of cellular compartment and membranes. Lipids in the form of fatty acids participate actively in the development of the nervous system at embryonic and early postnatal stage and are crucial for its maintenance throughout adulthood. The involvement of deregulated metabolism of lipids in many nervous system disorders, pathological conditions and injuries underscores the importance of lipids in maintaining normal cell signaling and tissue physiology. The correction of altered lipid levels by exogenous supply is considered as a most promising therapeutic approach. It is believed that they contribute in their own right by as yet incompletely understood mechanisms to those pathological processes. This article attempts to provide an overview of the lipid imbalances associated with CNS injury (traumatic brain injury, stroke, and spinal cord injury), neurological disorders (schizophrenia, anxiety, and depressive illnesses), and neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Fatty acids as biomarkers of diseases are briefly discussed as well as their therapeutic potential which will provide new insights to exploit these lipids to open new avenues for improving brain health, prevention, and treatment of nervous system disorders.

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Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite

Cited by 62 publications

References 403 publications

Hypothalamo-gastrointestinal axis – role in food intake regulation

Hypothalamo-gastrointestinal axis – role in food intake regulation

Appetite Regulatory Peptides and Insulin Resistance

Lipids, Brain, and Mental Health

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