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hypothalamic regulation of metabolism

Caroline André, Caterina Catania, Julie Remus-Borel, Elodie Ladeveze, Thierry Leste-Lasserre, Wilfrid Mazier, Elke Binder, Delphine Gonzales, Samantha Clark, Omar Guzman-Quevedo, Djoher Nora Abrous, Sophie Layé, Daniela Cota
Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation...
March 13, 2018: Brain, Behavior, and Immunity
Luba Sominsky, Christine L Jasoni, Hannah Twigg, Sarah J Spencer
The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adult function established postnatally, and maintained throughout adult life. The perinatal period is highly susceptible to environmental insults that, by disrupting critical developmental processes, can set the tone for the establishment of adult functionality...
March 15, 2018: Journal of Endocrinology
Takeshi Iwasa, Toshiya Matsuzaki, Kiyohito Yano, Mayila Yiliyasi, Akira Kuwahara, Sumika Matsui, Minoru Irahara
Energy balance and reproductive functions are closely linked in some species. The sex hormones (estrogens and androgens) are involved in the regulation of appetite, metabolism, body weight (BW), and body composition in mammals. Previously, we showed that the effects of testosterone on BW, appetite, and fat weight were markedly affected by alterations to the gonadal hormonal milieu. In this study, we examined whether testosterone administration changes food preferences and whether these effects of testosterone depend on gonadal status in female rats...
March 12, 2018: Behavioural Brain Research
Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
Xiao Ya Zhang, Xiangfang Zeng, Xutong Liu, Hongmin Jia, Pingli He, Shiyan Qiao, Xiangbing Mao
The objective of this study was to investigate whether valine (Val) supplementation in a reduced protein (RP) diet regulates growth performance associated with the changes in plasma amino acids (AAs) profile, metabolism, endocrine and neural system in piglets. Piglets or piglets with a catheter in the precaval vein were randomly assigned to two treatments, including two RP diets with standardized ileal digestible (SID) Val: Lysine (Lys) ratio of 0.45 and 0.65, respectively. The results indicated that piglets in the higher Val:Lys ratio treatment had higher average daily feed intake (ADFI) (P < 0...
March 10, 2018: Journal of Agricultural and Food Chemistry
Austin C Korgan, Elizabeth O'Leary, Jillian L King, Ian C G Weaver, Tara S Perrot
Paternal preconception risk factors (e.g. stress, diet, drug use) correlate with metabolic dysfunction in offspring, which is often comorbid with depressive and anxiety-like phenotypes. Detection of these risk factors or deleterious phenotypes informs a female about prevailing ecological demands, in addition to potential adverse environment-induced phenotypes that may be disseminated to her offspring. We examined whether a F0 male rat's prior exposure to an obesogenic high-fat diet (HFD) influences a female's attraction towards a male, subsequent mother-infant interactions and the development of defensive (emotional) responses in the F1 offspring...
February 21, 2018: Psychoneuroendocrinology
Ana Paula Toniazzo, Danusa M Arcego, Camilla Lazzaretti, Carine Lampert, Simone N Weis, Rodrigo Proto-Siqueira, Rachel Krolow, Carla Dalmaz
OBJECTIVE: Both stress exposure and high-fat diet (HFD) are contributors to the alarming prevalence of obesity. Leptin is secreted from adipose tissue and regulates appetite and body weight via the JAK-STAT3 pathway in the hypothalamus; it also regulates the hypothalamic-pituitary-thyroid axis, modulating energy homeostasis. Leptin signaling may be impaired by HFD intake, and here we investigate whether social isolation during the prepubertal period, associated with chronic HFD, can exert long-term effects on metabolic parameters in a sex-specific manner...
November 29, 2017: Nutrition
Ting Gong, Daniel J Torres, Marla J Berry, Matthew W Pitts
The hypothalamus is the central neural site governing food intake and energy expenditure. During the past 25 years, understanding of the hypothalamic cell types, hormones, and circuitry involved in the regulation of energy metabolism has dramatically increased. It is now well established that the adipocyte-derived hormone, leptin, acts upon two distinct groups of hypothalamic neurons that comprise opposing arms of the central melanocortin system. These two cell populations are anorexigenic neurons expressing proopiomelanocortin (POMC) and orexigenic neurons that express agouti-related peptide (AGRP)...
March 5, 2018: Free Radical Biology & Medicine
Peng Zhang, Henry Kuang, Yanlin He, Sharon O Idiga, Siming Li, Zhimin Chen, Zhao Yang, Xing Cai, Kezhong Zhang, Matthew J Potthoff, Yong Xu, Jiandie D Lin
Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling...
March 8, 2018: JCI Insight
Jun Xiang, Cuidong Bian, Xiaodong Wan, Qimin Zhang, Shengsong Huang, Denglong Wu
BACKGROUND: Obesity is a metabolic disease with a serious health burden in children and adults, and it induces a variety of conditions including subfecundity. Sleeve gastrectomy showed encouraging results in terms of weight loss and improve quality of life, and this study aimed to determine whether sleeve gastrectomy could reverse obesity-induced impaired fertility in male Sprague-Dawley rats. METHODS: After 16 weeks of a chow diet (CD) or a high-fat diet (HFD) challenge, rats on the HFD were given a sleeve gastrectomy or sham operation and then fed an HFD for another 8 weeks...
March 5, 2018: Obesity Surgery
María Rodríguez, Cristina Pintado, Eduardo Moltó, Nilda Gallardo, Carmen M Fernández-Martos, Virginia López, Antonio Andrés, Carmen Arribas
S-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation...
March 2, 2018: Scientific Reports
Giovanna Liguori, Simona Tafuri, Chika Miyoshi, Masashi Yanagisawa, Caterina Squillacioti, Valeria De Pasquale, Nicola Mirabella, Alfredo Vittoria, Anna Costagliola
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions...
February 26, 2018: Acta Histochemica
Oren Froy, Marta Garaulet
Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems...
February 27, 2018: Endocrine Reviews
Arleta K Skrzynska, Elisabetta Maiorano, Marco Bastaroli, Fatemeh Naderi, Jesús M Míguez, Gonzalo Martínez-Rodríguez, Juan M Mancera, Juan A Martos-Sitcha
The hypothalamus-pituitary-interrenal (HPI) and hypothalamus-sympathetic-chromaffin cell (HSC) axes are involved in the regulation of the stress response in teleost. In this regard, the activation of a complex network of endocrine players is needed, including corticotrophin-releasing hormone (Crh), Crh binding protein (Crhbp), proopiomelanocortin (Pomc), thyrotropin-releasing hormone (Trh), arginine vasotocin (Avt), and isotocin (It) to finally produce pleiotropic functions. We aimed to investigate, using the gilthead sea bream ( Sparus aurata ) as a biological model, the transcriptomic response of different endocrine factors ( crh, crhbp, pomc s, trh ), neuropeptides ( avt and it ), and their specific receptors ( avtrv1a, avtrv2 , and itr ) in four important target tissues (hypothalamus, pituitary, kidney and liver), after an acute stress situation...
2018: Frontiers in Physiology
Mina Desai, Monica G Ferrini, Guang Han, Juanita K Jellyman, Michael G Ross
In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured...
February 21, 2018: Environmental Research
Monika Rani, Raghuvansh Kumar, Pawan Krishan
Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX1 R) and orexin 2 receptor (OX2 R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons...
February 6, 2018: Neuropeptides
João C P Santiago, Markus Otto, Werner Kern, Paul Christian Baier, Manfred Hallschmid
The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in sleep/wake regulation and promotes food intake. We investigated the relationship between cerebrospinal fluid orexin A concentrations and body composition in non-narcoleptic human subjects with a wide range of body weight to gain insight into the role of orexin A in human metabolism. We collected cerebrospinal fluid and blood samples and measured body composition by bioelectric impedance analysis in 36 subjects (16 women and 20 men) with body mass indices between 16...
February 19, 2018: Peptides
Giuseppe Bruschetta, Sungho Jin, Jung Dae Kim, Sabrina Diano
OBJECTIVE: Prolyl carboxypeptidase (PRCP) plays a role in the regulation of energy metabolism by inactivating hypothalamic α-melanocyte stimulating hormone (α-MSH) levels. Although detected in the arcuate nucleus, limited PRCP expression has been observed in the arcuate POMC neurons, and its site of action in regulating metabolism is still ill-defined. METHODS: We performed immunostaining to assess the localization of PRCP in arcuate Neuropeptide Y/Agouti-related Peptide (NPY/AgRP) neurons...
February 8, 2018: Molecular Metabolism
Geun Hyang Kim, Guojun Shi, Diane Rm Somlo, Leena Haataja, Soobin Song, Qiaoming Long, Eduardo A Nillni, Malcolm J Low, Peter Arvan, Martin G Myers, Ling Qi
Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism...
February 19, 2018: Journal of Clinical Investigation
Karl Alexander Iwen, Rebecca Ölkrug, Georg Brabant
Thyroid hormones (TH) are of central importance for thermogenesis, energy homeostasis, and metabolism. Here we will discuss these aspects by focussing on the physiological aspects of TH-dependent regulation in response to cold exposure and fasting which will be compared to alterations in primary hyper- and hypothyroidism. In particular, we will summarise current knowledge on regional thyroid hormone status in the central nervous system (CNS) and in peripheral cells. In contrast to hyper- and hypothyroidism, where parallel changes are observed, local alterations in the CNS differ to peripheral compartments when induced by cold exposure or fasting...
February 6, 2018: Journal of Molecular Endocrinology
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