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Hypothalamic Neuronal Circuits Are Modulated by Insulin and Impact Metabolism 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Tadeu de Oliveira Diz, Sabela Casado, Rubén Nogueiras, Sulay Tovar
The ‘AgRP neurons’ are NPY (neuropeptide Y)/AgRP (agouti-related peptide) expressing neurones. These orexigenic neurons play a critical role in energy balance increasing food intake and body weight and decreasing energy expenditure and have a role in glucose homeostasis (26, 27). The activation of these neurons generates a liberation of AgRP, NPY and gamma-aminobutyric acid (GABA) to target other different hypothalamic neuronal populations (28).
Insulin Resistance and Glucose Regulation
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Leptin deficiency by birth (congenital) has been associated with hyperphagia, insulin resistance, hyperlipidaemia and impaired thermogenesis. Leptin directly suppresses appetite by inhibiting the orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP). Leptin also activates PI3K which is an important mechanism regulating glucose uptake by insulin signalling. Leptin has also been shown to activate AMPK, thus limiting the accumulation of triglycerides in hepatocytes and skeletal muscle cells, resulting in improved insulin signalling. Attenuation of leptin signalling at neuronal leptin receptors leads to increased accumulation of triglyceride in adipocytes, hepatocytes and skeletal muscle cells, resulting in insulin resistance at these major sites [41]. Leptin, in physiological amount, protects the peripheral skeletal muscle cells from lipotoxicity, but hyperleptinaemia leads to leptin resistance. Thus, a high leptin level or leptin resistance would not show its protective effects of a decreasing cellular lipid store and increasing insulin sensitivity, but rather would increase insulin resistance.
The Hungry Brain
Published in Emily Crews Splane, Neil E. Rowland, Anaya Mitra, Psychology of Eating, 2019
Emily Crews Splane, Neil E. Rowland, Anaya Mitra
Today, the arcuate nucleus, which is a small egg-shaped region at the midline base or bottom of the VMH (and usually damaged by the aforementioned VMH lesions), is known to be critical in the transduction or sensing of interoceptive, blood-borne hormones related to feeding. Two main types of cells, distinguished by the peptide transmitters that they express, are involved in this transduction. The first of these that we will examine in detail express agouti-related peptide (AgRP), and most if not all of these cells express a second transmitter, neuropeptide Y (NPY). The second class of neurons express the pro-opiomelanocortin (POMC) gene, and produce the transmitter α-MSH that engages melanocortin type 4 receptors (MC4R) in some brain regions.
Cardiac remodeling in obesity and after bariatric and metabolic surgery; is there a role for gastro-intestinal hormones?
Published in Expert Review of Cardiovascular Therapy, 2019
Elijah Sanches, Marieke Timmermans, Besir Topal, Alper Celik, Magnus Sundbom, Rui Ribeiro, Chetan Parmar, Surendra Ugale, Monika Proczko, Pieter S. Stepaniak, Juan Pujol Rafols, Kamal Mahawar, Marc P. Buise, Aleksandr Neimark, Rich Severin, Sjaak Pouwels
Leptin is an adipocyte-secreted hormone that circulates primarily at concentrations corresponding to the amount of fat tissue (this is the signaling of the long-term energy storage) and next to this the concentrations of leptin can change based on acute variations in the caloric intake [230]. Leptin can be seen as the regulator of the energy homeostasis because it could decrease the energy intake and increase the expenditure [230,231]. Leptin receptors can be found throughout the entire body and in the central nervous system [230]. Leptin regulates neuroendocrine function, which lead to behavior and energy expenditure [230,231]. Just like ghrelin, leptin can cross the blood-brain-barrier and in the brain, it interacts with the arcuate nucleus of the hypothalamus to regulate the energy homeostasis [187–189,230,231]. Here it stimulates pro-opiomelanocortin (POMC), which activates anorexigenic factors that inhibit caloric take in (e.g. α-melanocyte-stimulating hormone (αMSH) and it also inhibits orexigenic factors, like neuropeptide Y (NPY) and agouti-related peptide (AgRP), whom activation normally leads to an increase in food intake [230].
Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats
Published in Nutritional Neuroscience, 2019
Leandro Oliveira Batista, Viviane Wagner Ramos, Mariana Alejandra Rosas Fernández, Carlos Marcelo Concha Vilca, Kelse Tibau de Albuquerque
In addition to the action in the lipogenic pathway, Harrell et al.8 showed that the consumption of fructose by periadolescent rats altered the hormonal and behavioral profile related to the hypothalamic–pituitary axis, showing that the ingestion of fructose can influence gene and hormonal expression and lead to alterations in this axis. Furthermore, fructose is shown to present a potent pro-inflammatory effect in peripheral tissues,9 but few evidence shows this inflammatory effect on the central nervous system (CNS). It is known that hypothalamic inflammation alters peptides involved in the regulation of food intake, such as proopiomelanocortin (POMC) and agouti-related peptide (AgRP), and that evidence suggests that overnutrition can activate inflammatory pathways in hypothalamic regions.10,11
GPR17 receptor modulators and their therapeutic implications: review of recent patents
Published in Expert Opinion on Therapeutic Patents, 2019
Gabriella Marucci, Diego Dal Ben, Catia Lambertucci, Aleix Martí Navia, Andrea Spinaci, Rosaria Volpini, Michela Buccioni
Food intake is regulated by hypothalamic neurons expressing agouti-related peptide (AgRP). In particular, this peptide regulates eating and glucose metabolism. There are evidences that the ablation of FOXO1 in AgRP neurons reduced food intake, leads to slimming, improve glucose homeostasis, and increase sensitivity to insulin and leptin. GPR17 receptor is an effector of FOXO1 orexigenic signals in AgRP neurons. In fact, intra cerebroventricular injection of GPR17 receptor agonists induces food intake, while the GPR17 receptor antagonist, Cangrelor, curtails it. In addition, in AgRP-FOXO1 knockout mice, these effects are absent suggesting that GPR17 pharmacological modulation has therapeutic potential to treat obesity [22–24]. Accili et al. [28–30] made the first patent that identified GPR17 receptor as a new pathway involved in appetite and weight control. It was proved a strict correlation between AgRP-FOXO1 and GPR17 receptor. This observation allowed finding new methods of treating or preventing obesity and/or reducing appetite by administering a treatment able to reduce GPR17 receptor biological activity or its expression by a GPR17 receptor antagonist or inhibitory oligonucleotide of siRNA, respectively. The inhibition of GPR17 receptor activity could be used in a subject having impaired glucose tolerance or low insulin sensitivity because this increases glucose tolerance and/or insulin sensitivity. On the other hand, by GPR17 receptor activating could be treated eating disorders such as anorexia that are associated with abnormal weight loss.