Peripheral Signals Conveying Metabolic Information to the Brain: Short-Term and Long-Term Regulation of Food Intake and Energy Homeostasis

The control of food intake and body weight by the brain relies upon the detection and integration of signals reflecting energy stores and fluxes, and their interaction with many different inputs related to food palatability and gastrointestinal handling as well as social, emotional, circadian, habitual and other situational factors. This review focuses upon the role of hormones secreted by the endocrine pancreas: hormones, which individually and collectively influence food intake, with an emphasis upon insulin, glucagon and amylin. Insulin and amylin are co-secreted by B-cells and provide a signal that reflects both circulating energy in the form of glucose and stored energy in the form of visceral adipose tissue. Insulin acts directly at the liver to suppress the synthesis and secretion of glucose, and some plasma insulin is transported into the brain and especially the mediobasal hypothalamus where it elicits a net catabolic response, particularly reduced food intake and loss of body weight. Amylin reduces meal size by stimulating neurons in the hindbrain, and there is evidence that amylin additionally functions as an adiposity signal controlling body weight as well as meal size. Glucagon is secreted from A-cells and increases glucose secretion from the liver. Glucagon acts in the liver to reduce meal size, the signal being relayed to the brain via the vagus nerves. To summarize, hormones of the endocrine pancreas are collectively at the crossroads of many aspects of energy homeostasis. Glucagon and amylin act in the short term to reduce meal size, and insulin sensitizes the brain to short-term meal-generated satiety signals; and insulin and perhaps amylin as well act over longer intervals to modulate the amount of fat maintained and defended by the brain. Hormones of the endocrine pancreas interact with receptors at many points along the gut–brain axis, from the liver to the sensory vagus nerve to the hindbrain to the hypothalamus; and their signals are conveyed both neurally and humorally. Finally, their actions include gastrointestinal and metabolic as well as behavioural effects.

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Gastric leptin: a putative role in the short-term regulation of food intake

British Journal Of Nutrition ◽

10.1079/bjn2003945 ◽

2003 ◽

Vol 90 (4) ◽

pp. 735-741 ◽

Cited By ~ 53

Author(s):

Catalina Picó ◽

Paula Oliver ◽

Juana Sánchez ◽

Andreu Palou

Keyword(s):

Food Intake ◽

Cell Type ◽

Digestive Physiology ◽

Short Term ◽

Fat Depots ◽

Short And Long Term ◽

Endocrine Cell Type ◽

The Brain

The discovery of the production of leptin by the stomach, in addition to its production by adipose tissue, has initiated new investigation into the possible role of this protein in the digestive physiology, in particular in the short-term control of energy balance. Leptin has been identified in the lower half of the stomach glands both in the pepsinogen granules of chief cells and in the granules of a specific endocrine cell type, suggesting that leptin action is exerted by both exocrine and endocrine pathways. Gastric leptin is sensitive to the nutritional state, being rapidly mobilized in response to food intake following fasting, or after the administration of satiety factors; this suggests a role for this protein in the short-term regulation of feeding, acting in collaboration with satiety peptides such as cholecystokinin. Leptin, produced by gastric cells and by adipocytes, could act on both acute and chronic regulation of feeding behaviour respectively, giving information to the brain on the availability of external (food) and internal (fat depots) energy resources, thus participating in short- and long-term satiation.

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Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

Mediators of Inflammation ◽

10.1155/2015/801685 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Alessio Molfino ◽

Gianfranco Gioia ◽

Filippo Rossi Fanelli ◽

Alessandro Laviano

Keyword(s):

Adipose Tissue ◽

Food Intake ◽

Proinflammatory Cytokines ◽

Adaptive Response ◽

Energy Homeostasis ◽

Cancer Cachexia ◽

Behavioral Changes ◽

Brain Areas ◽

Functional Changes ◽

The Brain

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

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Short-term and long-term international scientific mobility of Italian PhDs: An analysis by gender

Proceedings e report - ASA 2021 Statistics and Information Systems for Policy Evaluation ◽

10.36253/978-88-5518-304-8.08 ◽

2021 ◽

pp. 35-40

Author(s):

Valentina Tocchioni ◽

Alessandra Petrucci ◽

Alessandra Minello

Keyword(s):

Multinomial Logistic Regression ◽

Early Career ◽

International Mobility ◽

Short Term ◽

Host Countries ◽

Academic Mobility ◽

Positive Effects ◽

Long Run ◽

The Brain

In the last years, there has been a large increase in high-educated and high-skilled people’s mobility as a consequence of the internationalization and globalization, the weakening of research and university systems of sending countries (the “brain drain” process), the increase in skilled demand and improvements in higher education of host countries (the “brain gain” process). At the micro-level, academic mobility has positive consequences on occupational prospects and careers of researchers, both in the short- and long- run. Nevertheless, numerous research studies have demonstrated the challenges of engaging in international academic mobility for people with caring responsibilities, particularly women. Using Italian data on occupational conditions of PhDs collected in 2018 by Istat and modelling multinomial logistic regression analyses, we intend to verify if female researchers are associated with a lower international mobility irrespective their field of study, and the extent to which gender interacts differently in the various fields of study in affecting the probability of moving abroad after PhD qualification. Also, the distinction between long-term and short-term mobility, which has been mainly neglected in the literature concentrating on longer stays, has taken into account. In this respect, short-term mobility is a potentially high-value investment that may be pursued also by those researchers and scientists who cannot move for longer periods, such as women with caring responsibilities. In the literature, it is acknowledged that an experience abroad during early career may have positive effects on future occupational prospects. With our work, we intend to shed light on potential disparities on moving abroad that may exist among researchers in their early career by gender, and which could contribute to leave behind women in academia.

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Functional Connectivity within Brain Networks of Long Term and Short term Meditators

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.b1120.1292s19 ◽

2019 ◽

Vol 9 (2S) ◽

pp. 29-34

Keyword(s):

Functional Connectivity ◽

Temporal Correlation ◽

Brain Regions ◽

Invasive Technique ◽

Long Term Effects ◽

Short Term ◽

Statistical Concept ◽

The Brain ◽

Meditative Practices

Meditation refers to a state of mind of relaxation and concentration, where generally the mind and body is at rest. The process of meditation reflects the state of the brain which is distinct from sleep or typical wakeful states of consciousness. Meditative practices usually involve regulation of emotions and monitoring of attention. Over the past decade there has been a tremendous increase in an interest to study the neural mechanisms involved in meditative practices. It could also be beneficial to explore if the effect of meditation is altered by the number of years of meditation practice. Functional Magnetic Resonance Imaging (fMRI) is a very useful imaging technique which can be used to perform this analysis due to its inherent benefits, mainly it being a non-invasive technique. Functional activation and connectivity analysis can be performed on the fMRI data to find the active regions and the connectivity in the brain regions. Functional connectivity is defined as a simple temporal correlation between anatomically separate, active neural regions. Functional connectivity gives the statistical dependencies between regional time series. It is a statistical concept and is quantified using metrics like Correlation. In this study, a comparison is made between functional connectivity in the brain regions of long term meditation practitioners (LTP) and short-term meditation practitioners (STP) to see the differences and similarities in the connectivity patterns. From the analysis, it is evident that in fact there is a difference in connectivity between long term and short term practitioners and hence continuous practice of meditation can have long term effects.

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Prolonged retention of the anorectic cobalt protoporphyrin in the hypothalamus and the resulting expression of Fos

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00055.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. R465-R471 ◽

Cited By ~ 6

Author(s):

Richard A. Galbraith ◽

Ilean Hodgdon ◽

Michele S. Grimm ◽

Margaret A. Vizzard

Keyword(s):

Male Rats ◽

Halothane Anesthesia ◽

Short Term ◽

Brain Areas ◽

Duration Of Action ◽

Prolonged Duration ◽

Cobalt Protoporphyrin ◽

Prolonged Retention ◽

The Brain

The anorectic cobalt protoporphyrin (CoPP) is known to elicit short-term hypophagia and long-term weight loss through unknown mechanisms in the brains of experimental animals. The goal of this work was to determine 1) if the prolonged duration of action of CoPP is related to its prolonged retention within the brain; and 2) with the use of immunohistochemical detection of Fos, the product of the early-immediate gene c-fos, which cells are activated after exposure to CoPP. These studies were carried out in male rats after intracerebroventricular administration of CoPP, 0.4 μmol/kg body wt, given under light halothane anesthesia. Residence of CoPP in the brain was determined by residual counts in dissected brains of 57CoPP-injected rats. Fos immunoreactivity was mapped in coronal sections of rat brains 4–6 h after injection with CoPP. The results showed that 57CoPP was retained in the hypothalamus preferentially compared with the cortex of the brain and could be detected in the hypothalamus for in excess of 5 wk. Fos activation was increased by CoPP, detected predominantly in neuronal rather than glial cells, and was markedly more robust in the hypothalamus than in other brain areas. Thus CoPP remains in the hypothalamus for prolonged periods and activates Fos expression in the hypothalamus.

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A comparison of the effects of body condition and short-term food restriction on the feeding behaviour of sheep

Proceedings of the British Society of Animal Science ◽

10.1017/s0308229600031408 ◽

1996 ◽

Vol 1996 ◽

pp. 174-174

Author(s):

A.M. Sibbald

Keyword(s):

Food Intake ◽

Body Condition ◽

Feeding Behaviour ◽

Food Restriction ◽

Term Effect ◽

Short Term ◽

Daily Food ◽

Long Term Effect ◽

Single Meal

Voluntary food intake is generally inversely related to body condition or fatness in mature sheep (Foot, 1972). Since the intake of pelleted diets by housed sheep consists of a number of discrete feeding bouts or 'meals' (e.g. Bermudez et al., 1989), the relatively long-term effect of body condition on intake will be achieved through changes in feeding behaviour at the level of a single meal. The aim of this experiment was to compare the effects of body condition and short-term food restriction on meal patterns in sheep, to investigate the mechanism by which body condition influences daily food intake.

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Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

Nutrition Research Reviews ◽

10.1017/s0954422411000035 ◽

2011 ◽

Vol 24 (1) ◽

pp. 132-154 ◽

Cited By ~ 12

Author(s):

V. Somogyi ◽

A. Gyorffy ◽

T. J. Scalise ◽

D. S. Kiss ◽

G. Goszleth ◽

...

Keyword(s):

Food Intake ◽

Energy Expenditure ◽

Thyroid Hormones ◽

Energy Homeostasis ◽

The Body ◽

Feedback Information ◽

Hypothalamic Regulation ◽

The Individual ◽

Desire To Eat ◽

The Brain

Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five best-known peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake.

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LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

Endocrinology ◽

10.1210/en.2013-1550 ◽

2014 ◽

Vol 155 (2) ◽

pp. 429-440 ◽

Cited By ~ 11

Author(s):

Ji-Yao Li ◽

Biaoxin Chai ◽

Weizhen Zhang ◽

Danielle M. Fritze ◽

Chao Zhang ◽

...

Keyword(s):

In Situ Hybridization ◽

Food Intake ◽

Neuropeptide Y ◽

Paraventricular Nucleus ◽

Median Eminence ◽

Energy Homeostasis ◽

Male Rats ◽

The Third ◽

The Brain

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

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The Antiobesity Effects of Centrally Administered Neuromedin U and Neuromedin S Are Mediated Predominantly by the Neuromedin U Receptor 2 (NMUR2)

Endocrinology ◽

10.1210/en.2008-1772 ◽

2009 ◽

Vol 150 (7) ◽

pp. 3101-3109 ◽

Cited By ~ 47

Author(s):

Andrea Peier ◽

Jennifer Kosinski ◽

Kimberly Cox-York ◽

Ying Qian ◽

Kunal Desai ◽

...

Keyword(s):

Food Intake ◽

Energy Homeostasis ◽

Central Administration ◽

Diet Induced Obesity ◽

Inhibit Food Intake ◽

Selective Agonists ◽

Treatment Of Obesity ◽

The Brain ◽

Deficient Mice

Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis. Pharmacological data have shown that NMU and NMS inhibit food intake when administered centrally and that NMU increases energy expenditure. Additionally, NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU are lean and hypophagic. Two high-affinity NMU/NMS receptors, NMUR1 and NMUR2, have been identified. NMUR1 is predominantly expressed in the periphery, whereas NMUR2 is predominantly expressed in the brain, suggesting that the effects of centrally administered NMU and NMS are mediated by NMUR2. To evaluate the role of NMUR2 in the regulation of energy homeostasis, we characterized NMUR2-deficient (Nmur2−/−) mice. Nmur2−/− mice exhibited a modest resistance to diet-induced obesity that was at least in part due to reduced food intake. Acute central administration of NMU and NMS reduced food intake in wild-type but not in Nmur2−/− mice. The effects on activity and core temperature induced by centrally administered NMU were also absent in Nmur2−/− mice. Moreover, chronic central administration of NMU and NMS evoked significant reductions in body weight and sustained reductions in food intake in mice. In contrast, Nmur2−/− mice were largely resistant to these effects. Collectively, these data demonstrate that the anorectic and weight-reducing actions of centrally administered NMU and NMS are mediated predominantly by NMUR2, suggesting that NMUR2-selective agonists may be useful for the treatment of obesity.

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