Molecular Mechanisms Involved in the Regulation of Food Intake

2014 ◽  
pp. 87-100
Author(s):  
Emilio González-Jiménez
Keyword(s):  
Food Intake ◽  
Molecular Mechanisms

scholarly journals Central administration of sodium-glucose cotransporter-2 inhibitors increases food intake involving adenosine monophosphate-activated protein kinase phosphorylation in the lateral hypothalamus in healthy rats

2021 ◽  
Vol 9 (1) ◽  
pp. e002104
Author(s):  
Kenji Takeda ◽  
Hiraku Ono ◽  
Ko Ishikawa ◽  
Tomohiro Ohno ◽  
Jin Kumagai ◽  
...  
Keyword(s):  
Food Intake ◽  
Lateral Hypothalamus ◽  
Molecular Mechanisms ◽  
Intraperitoneal Administration ◽  
Adenosine Monophosphate ◽  
Sglt2 Inhibitors ◽  
Central Administration ◽  
Hypothalamic Area ◽  
Sodium Glucose Cotransporter ◽  
Increase Food Intake

IntroductionSodium glucose cotransporter-2 (SGLT2) inhibitors are widely used for diabetes treatment. Although SGLT2 inhibitors have been clinically observed to increase food intake, roles or even the presence of SGLT2 in the central nervous system (CNS) has not been established. We aimed to elucidate potential functions of SGLT2 in the CNS, and the effects of CNS-targeted SGLT2 inhibitors on food intake.Research design and methodsWe administered three kinds of SGLT2 inhibitors, tofogliflozin, dapagliflozin, and empagliflozin, into the lateral ventricle (LV) in rats and evaluated their effects on food intake. We also evaluated the effects of tofogliflozin administration in the third (3V) and fourth ventricle (4V). Intraperitoneal administration of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress food intake, was combined with central tofogliflozin to elucidate whether GLP-1 signaling antagonizes the effect of central SGLT2 inhibitors on food intake. To elucidate potential molecular mechanisms mediating changes in feeding, hypothalamic areas associated with food intake regulation were harvested and analyzed after intracerebroventricular administration (ICV) of tofogliflozin.ResultsBolus ICV injection of tofogliflozin induced a robust increase in food intake starting at 1.5 hours postinjection, and lasting for 5 days. No effect was observed when the same dose of tofogliflozin was administered intraperitoneally. ICV dapagliflozin and empagliflozin significantly enhanced food intake, although the strength of these effects varied among drugs. Food intake was most markedly enhanced when tofogliflozin was infused into the LV. Fewer or no effects were observed with infusion into the 3V or 4V, respectively. Systemic administration of liraglutide suppressed the effect of ICV tofogliflozin on food intake. ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.ConclusionsSGLT2 inhibitors in the CNS increase food intake. SGLT2 activity in the CNS may regulate food intake through AMPK phosphorylation in the lateral hypothalamic area.

scholarly journals Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

2012 ◽  
Vol 303 (12) ◽  
pp. E1446-E1458 ◽  
Author(s):  
Xinxia Zhu ◽  
Stephanie M. Krasnow ◽  
Quinn R. Roth-Carter ◽  
Peter R. Levasseur ◽  
Theodore P. Braun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Amino Acid ◽  
Food Intake ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Deficient Diet ◽  
Indispensable Amino Acid ◽  
Brown Adipose ◽  
Melanocortin Signaling

Animals exhibit a rapid and sustained anorexia when fed a diet that is deficient in a single indispensable amino acid (IAA). The chemosensor for IAA deficiency resides within the anterior piriform cortex (APC). Although the cellular and molecular mechanisms by which the APC detects IAA deficiency are well established, the efferent neural pathways that reduce feeding in response to an IAA-deficient diet remain to be fully characterized. In the present work, we investigated whether 1) central melanocortin signaling is involved in IAA deficiency-induced anorexia (IAADA) and 2) IAADA engages other key appetite-regulating neuronal populations in the hypothalamus. Rats and mice that consumed a valine-deficient diet (VDD) for 2–3 wk exhibited marked reductions in food intake, body weight, fat and lean body mass, body temperature, and white adipose tissue leptin gene expression, as well as a paradoxical increase in brown adipose tissue uncoupling protein-1 mRNA. Animals consuming the VDD had altered hypothalamic gene expression, typical of starvation. Pharmacological and genetic blockade of central melanocortin signaling failed to increase long-term food intake in this model. Chronic IAA deficiency was associated with a marked upregulation of corticotropin-releasing hormone expression in the lateral hypothalamus, particularly in the parasubthalamic nucleus, an area heavily innervated by efferent projections from the APC. Our observations indicate that the hypothalamic melanocortin system plays a minor role in acute, but not chronic, IAADA and suggest that the restraint on feeding is analogous to that observed after chronic dehydration.

scholarly journals Associations between dairy consumption and body weight: a review of the evidence and underlying mechanisms

2011 ◽  
Vol 24 (1) ◽  
pp. 72-95 ◽  
Author(s):  
Anestis Dougkas ◽  
Christopher K. Reynolds ◽  
Ian D. Givens ◽  
Peter C. Elwood ◽  
Anne M. Minihane
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Molecular Mechanisms ◽  
Dairy Product ◽  
Energy Restriction ◽  
Appetite Regulation ◽  
Dairy Consumption ◽  
Underlying Mechanisms ◽  
The Impact

As the incidence of obesity is reaching ‘epidemic’ proportions, there is currently widespread interest in the impact of dietary components on body-weight and food intake regulation. The majority of data available from both epidemiological and intervention studies provide evidence of a negative but modest association between milk and dairy product consumption and BMI and other measures of adiposity, with indications that higher intakes result in increased weight loss and lean tissue maintenance during energy restriction. The purported physiological and molecular mechanisms underlying the impact of dairy constituents on adiposity are incompletely understood but may include effects on lipolysis, lipogeneis and fatty acid absorption. Furthermore, accumulating evidence indicates an impact of dairy constituents, in particular whey protein derivatives, on appetite regulation and food intake. The present review summarises available data and provides an insight into the likely contribution of dairy foods to strategies aimed at appetite regulation, weight loss or the prevention of weight gain.

Molecular mechanisms underlying anorexia nervosa: Focus on human gene association studies and systems controlling food intake

2010 ◽  
Vol 62 (2) ◽  
pp. 147-164 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Pawel K. Olszewski ◽  
Allen S. Levine ◽  
Helgi B. Schiöth
Keyword(s):  
Anorexia Nervosa ◽  
Food Intake ◽  
Molecular Mechanisms ◽  
Human Gene ◽  
Association Studies ◽  
Gene Association

scholarly journals Loss and gain of function experiments implicate TMEM18 as a mediator of the strong association between genetic variants at human Chromosome 2p25.3 and obesity

2017 ◽  
Author(s):  
Rachel Larder ◽  
M. F. Michelle Sim ◽  
Pawan Gulati ◽  
Robin Antrobus ◽  
Y.C. Loraine Tung ◽  
...  
Keyword(s):  
Food Intake ◽  
Human Chromosome ◽  
Nuclear Membrane ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Strong Association ◽  
Nuclear Pore ◽  
Chromosome 2 ◽  
The Impact

AbstractAn intergenic region of human Chromosome 2 (2p25.3) harbours genetic variants which are among those most strongly and reproducibly associated with obesity. The molecular mechanisms mediating these effects remain entirely unknown. The gene closest to these variants is TMEM18, encoding a transmembrane protein localised to the nuclear membrane. The expression of Tmem18 within the murine hypothalamic paraventricular nucleus was altered by changes in nutritional state, with no significant change seen in three other closest genes. Germline loss of Tmem18 in mice resulted in increased body weight, which was exacerbated by high fat diet and driven by increased food intake. Selective overexpression of Tmem18 in the PVN of wild-type mice reduced food intake and also increased energy expenditure. We confirmed the nuclear membrane localisation of TMEM18 but provide new evidence that it is has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex. Our data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity.

Topiramate Treatment Improves Hypothalamic Insulin and Leptin Signaling and Action and Reduces Obesity in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4401-4411 ◽  
Author(s):  
Andrea M. Caricilli ◽  
Erica Penteado ◽  
Lélia L. de Abreu ◽  
Paula G. F. Quaresma ◽  
Andressa C. Santos ◽  
...  
Keyword(s):  
Food Intake ◽  
Molecular Mechanisms ◽  
Janus Kinase ◽  
Mrna Levels ◽  
Obese Mice ◽  
Short Term ◽  
Short Term Treatment ◽  
Peripheral Tissues ◽  
Leptin Signaling ◽  
Brown Adipose

Topiramate (TPM) treatment has been shown to reduce adiposity in humans and rodents. The reduction in adiposity is related to decreased food intake and increased energy expenditure. However, the molecular mechanisms through which TPM induces weight loss are contradictory and remain to be clarified. Whether TPM treatment alters hypothalamic insulin, or leptin signaling and action, is not well established. Thus, we investigate herein whether short-term TPM treatment alters energy balance by affecting insulin and leptin signaling, action, or neuropeptide expression in the hypothalamus of mice fed with a high-fat diet. As expected, short-term treatment with TPM diminished adiposity in obese mice mainly due to reduced food intake. TPM increased anorexigenic signaling by enhancing the leptin-induced leptin receptor/Janus kinase 2/signal transducer and activator of transcription 3 pathway and the insulin-induced insulin receptor substrate/Akt/forkhead box O1 pathway in parallel to reduced phosphatase protein expression in the hypothalamus of obese mice. These effects were independent of body weight. TPM also raised anorexigenic neuropeptides such as POMC, TRH, and CRH mRNA levels in obese mice. In addition, TPM increased the activation of the hypothalamic MAPK/ERK pathway induced by leptin, accompanied by an increase in peroxisome proliferator-activated receptor-coactivator α and uncoupling protein 1 protein levels in brown adipose tissue. Furthermore, TPM increased AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation in peripheral tissues, which may help improve energy metabolism in these tissues. Together, these results provide novel insights into the molecular mechanisms through which TPM treatment reduces adiposity.

Estrous Cycle Modulation of Feeding and Relaxin-3/Rxfp3 mRNA Expression - Implications for Estradiol

2020 ◽  
Author(s):  
Camila de Ávila ◽  
Sandrine Chometton ◽  
Juliane Calvez ◽  
Geneviève Guèvremont ◽  
Alan Kania ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Food Intake ◽  
Estrous Cycle ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Female Rats ◽  
Type I ◽  
Mrna Levels ◽  
Female Rat ◽  
Relaxin Family

Introduction: Food intake varies during the ovarian hormone/estrous cycle in humans and rodents, an effect mediated mainly by estradiol. A potential mediator of the central anorectic effects of estradiol is the neuropeptide relaxin-3 (RLN3) synthetised in the nucleus incertus (NI) and acting via the relaxin-family peptide-3 receptor (RXFP3). Methods: We investigated the relationship of RLN3/RXFP3 signaling and feeding behavior across the female rat estrous cycle. We used in situ hybridization to investigate expression patterns of Rln3 mRNA in NI and Rxfp3 mRNA in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamic area (LHA), medial preoptic area (MPA), and bed nucleus of the stria terminalis (BNST), across the estrous cycle. We identified expression of estrogen receptors in the NI using droplet digital polymerase-chain reaction and assessed the electrophysiological responsiveness of NI neurons to estradiol in brain slices. Results: Rln3 mRNA reached the lowest levels in the NI pars compacta during proestrus. Rxfp3 mRNA levels varied across the estrous cycle in a region-specific manner, with changes observed in the perifornical LHA, magnocellular PVN, dorsal BNST, and MPA, but not in the parvocellular PVN or lateral LHA. G protein-coupled estrogen receptor-1 (Gper1) mRNA was the most abundant estrogen receptor transcript in the NI. Estradiol inhibited 33% of type I NI neurons, including RLN3-positive cells. Conclusion: These findings demonstrate that the RLN3/RXFP3 system is modulated by the estrous cycle and although further studies are required to better elucidate the cellular and molecular mechanisms of estradiol signaling, current results implicate the involvement of RLN3/RXFP3 system in food intake fluctuations observed across the estrous cycle in female rats.

Involvement of central microsomal prostaglandin E synthase-1 in IL-1β-induced anorexia

2006 ◽  
Vol 25 (3) ◽  
pp. 485-492 ◽  
Author(s):  
E. Pecchi ◽  
M. Dallaporta ◽  
S. Thirion ◽  
C. Salvat ◽  
F. Berenbaum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Molecular Mechanisms ◽  
Sickness Behavior ◽  
Prostaglandin E ◽  
Concomitant Reduction ◽  
Intracerebroventricular Injections ◽  
Feeding Control ◽  
Significant Health

In response to infection or inflammation, individuals develop a set of symptoms referred to as sickness behavior, which includes a decrease in food intake. The characterization of the molecular mechanisms underlying this hypophagia remains critical, because chronic anorexia may represent a significant health risk. Prostaglandins (PGs) constitute an important inflammatory mediator family whose levels increase in the brain during inflammatory states, and their involvement in inflammatory-induced anorexia has been proposed. The microsomal PGE synthase (mPGES)-1 enzyme is involved in the last step of PGE2 biosynthesis, and its expression is stimulated by proinflammatory agents. The present study attempted to determine whether an upregulation of mPGES-1 gene expression may account for the immune-induced anorexic behavior. We focused our study on mPGES-1 expression in the hypothalamus and dorsal vagal complex, two structures strongly activated during peripheral inflammation and involved in the regulation of food intake. We showed that mPGES-1 gene expression was robustly upregulated in these structures after intraperitoneal and intracerebroventricular injections of anorexigenic doses of IL-1β. This increase was correlated with the onset of anorexia. The concomitant reduction in food intake and central mPGES-1 gene upregulation led us to test the feeding behavior of mice lacking mPGES-1 during inflammation. Interestingly, IL-1β failed to decrease food intake in mPGES-1−/− mice, although these animals developed anorexia in response to a PGE2 injection. Taken together, our results demonstrate that mPGES-1, which is strongly upregulated during inflammation in central structures involved in feeding control, is essential for immune anorexic behavior and thus may constitute a potential therapeutic target.

scholarly journals Neuropeptidergic Control of Feeding: Focus on the Galanin Family of Peptides

2021 ◽  
Vol 22 (5) ◽  
pp. 2544
Author(s):  
P. Marcos ◽  
R. Coveñas
Keyword(s):  
Food Intake ◽  
Feeding Behaviour ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Metabolic Complications ◽  
Y1 Receptor ◽  
Hypothalamic Nuclei ◽  
Receptor Interactions ◽  
Important Health ◽  
Other Substances

Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet.

scholarly journals Ghrelin: a hormone regulating food intake and energy homeostasis

2006 ◽  
Vol 96 (2) ◽  
pp. 201-226 ◽  
Author(s):  
Mercedes Gil-Campos ◽  
Concepción María Aguilera ◽  
Ramón Cañete ◽  
Angel Gil
Keyword(s):  
Food Intake ◽  
Regulatory Networks ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Growth Hormone Secretagogue ◽  
Orexigenic Peptide ◽  
Acyl Ghrelin ◽  
Amp Activated Protein Kinase ◽  
Agouti Related Protein

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.

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