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

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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Effects of Peripherally Administered Neuromedin U on Energy and Glucose Homeostasis

Endocrinology ◽

10.1210/en.2010-1463 ◽

2011 ◽

Vol 152 (7) ◽

pp. 2644-2654 ◽

Cited By ~ 33

Author(s):

Andrea M. Peier ◽

Kunal Desai ◽

James Hubert ◽

Xiaobing Du ◽

Liming Yang ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

Energy Homeostasis ◽

Core Body Temperature ◽

Vagal Afferents ◽

Core Body ◽

Diabetes And Obesity ◽

The Brain

Neuromedin U (NMU) is a highly conserved peptide reported to modulate energy homeostasis. Pharmacological studies have shown that centrally administered NMU inhibits food intake, reduces body weight, and increases energy expenditure. NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU become lean and hypophagic. Two high-affinity NMU receptors, NMUR1 and NMUR2, have been identified. NMUR1 is found primarily in the periphery and NMUR2 primarily in the brain, where it mediates the anorectic effects of centrally administered NMU. Given the broad expression pattern of NMU, we evaluated whether peripheral administration of NMU has effects on energy homeostasis. We observed that acute and chronic peripheral administration of NMU in rodents dose-dependently reduced food intake and body weight and that these effects required NMUR1. The anorectic effects of NMU appeared to be partly mediated by vagal afferents. NMU treatment also increased core body temperature and metabolic rate in mice, suggesting that peripheral NMU modulates energy expenditure. Additionally, peripheral administration of NMU significantly improved glucose excursion. Collectively, these data suggest that NMU functions as a peripheral regulator of energy and glucose homeostasis and the development of NMUR1 agonists may be an effective treatment for diabetes and obesity.

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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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Nutritional demands in acute and chronic illness

Proceedings of The Nutrition Society ◽

10.1079/pns2003302 ◽

2003 ◽

Vol 62 (4) ◽

pp. 777-781 ◽

Cited By ~ 21

Author(s):

Rosemary A. Richardson ◽

H. Isobel M. Davidson

Keyword(s):

Energy Expenditure ◽

Inflammatory Response ◽

Energy Homeostasis ◽

Negative Energy ◽

Disease States ◽

Energy Needs ◽

Sufficient Energy ◽

Effective Treatment Modality ◽

The Individual

Common to both acute and chronic disease are disturbances in energy homeostasis, which are evidenced by quantitative and qualitative changes in dietary intake and increased energy expenditure. Negative energy balance results in loss of fat and lean tissue. The management of patients with metabolically-active disease appears to be simple; it would involve the provision of sufficient energy to promote tissue accretion. However, two fundamental issues serve to prevent nutritional demands in disease being met. The determination of appropriate energy requirements relies on predictive formulae. While equations have been developed for critically-ill populations, accurate energy prescribing in the acute setting is uncommon. Only 25–32% of the patients have energy intakes within 10% of their requirements. Clearly, the variation in energy expenditure has led to difficulties in accurately defining the energy needs of the individual. Second, the acute inflammatory response initiated by the host can have profound effects on ingestive behaviour, but this area is poorly understood by practising clinicians. For example, nutritional targets have been set for specific disease states, i.e. pancreatitis 105–147 KJ (25–35 kcal)/kg; chronic liver disease 147–168 kj (35–40 kcl)/kg, but given the alterations in gut physiology that accompany the acute-phase response, targets are unlikely to be met. In cancer cachexia attenuation of the inflammatory response using eicosapentaenoic acid results in improved nutritional intake and status. This strategy poses an attractive proposition in the quest to define nutritional support as a clinically-effective treatment modality in other disorders.

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Hibiscus sabdariffa tea affects diet-induced thermogenesis and subjective satiety responses in healthy men, but not in women: a randomized crossover trial

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2021-0051 ◽

2021 ◽

Author(s):

Natália Cristina de Faria ◽

Ana Paula da Costa Soares ◽

Guilherme Fonseca Graciano ◽

Maria Isabel Toulson Davisson Correia ◽

Magda Carvalho Pires ◽

...

Keyword(s):

Clinical Trial ◽

Food Intake ◽

Energy Expenditure ◽

Resting Energy Expenditure ◽

Hibiscus Sabdariffa ◽

Clinical Trial Registry ◽

Open Label ◽

Satiety Response ◽

Diet Induced Thermogenesis ◽

Desire To Eat

The aim of this study was to investigate the effect of Hibiscus sabdariffa tea on energy expenditure, satiety response and food intake. This is an open-label, crossover, randomized clinical trial (RBR-5HZ86T), including 21 subjects (11 women, 10 men). The individuals were evaluated at acute moments (fasting and after eating standardized breakfast accompanied by water or Hibiscus sabdariffa tea). Resting energy expenditure was measured by indirect calorimetry, subjective satiety responses were evaluated with a visual analogue scale and food intake was assessed by using food records. The volunteers who drank the Hibiscus sabdariffa tea had lower perception of hunger (p=0.002) and greater feeling of satiety (p=0.010) and fullness (p=0.009) compared to control. Men who ingested the Hibiscus sabdariffa tea had an increase in nitrogen energy expenditure (water: 1501±290.7kcal, Hibiscus sabdariffa tea: 1619±288.9kcal; p=0.029). In comparison to control, men presented less perception of hunger (p=0.003) and desire to eat (p=0.016), increased satiety (p=0.021) and fullness (p=0.010), and women oxidized more fat (p=0.034) when they drank Hibiscus sabdariffa tea. There was no difference between treatments regarding the energy and macronutrient intake from the first meal and throughout the day (p>0.050) for all participants. The Hibiscus sabdariffa tea only affected energy expenditure and satiety responses in men. Clinical trial registry: ReBEC Platform of the Brazilian Clinical Trials Registry - RBR-5HZ86T Novelty bullets • Hibiscus sabdariffa tea promoted an increase in energy expenditure and caused less perception of hunger/desire to eat in men. • Hibiscus sabdariffa tea intake increased postprandial fat oxidation in women.

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Genealogy of the Cerebral Subject

Being Brains ◽

10.5422/fordham/9780823276073.003.0002 ◽

2017 ◽

Author(s):

Fernando Vidal ◽

Francisco Ortega

Keyword(s):

Nineteenth Century ◽

Functional Neuroimaging ◽

The Body ◽

Self Help ◽

Brain Structure And Function ◽

Cerebral Subject ◽

The Individual ◽

And Function ◽

Cerebral Self ◽

The Brain

The first chapter proposes to trace the distant roots of the cerebral subject to the late seventeenth century, and particularly to debates about the seat of the soul, the corpuscularian theory of matter, and John Locke’s philosophy of personal identity. In the wake of Locke, eighteenth century authors began to assert that the brain is the only part of the body we need to be ourselves. In the nineteenth century, this form of deterministic essentialism contributed to motivate research into brain structure and function, and in turn confirmed the brain-personhood nexus. Since then, from phrenology to functional neuroimaging, neuroscientific knowledge and representations have constituted a powerful support for prescriptive outlooks on the individual and society. “Neuroascesis,” as we call the business that sells programs of cerebral self-discipline, is a case in point, which this chapter also examines. It appeals to the brain and neuroscience as bases for its self-help recipes to enhance memory and reasoning, fight depression, anxiety and compulsions, improve sexual performance, achieve happiness, and even establish a direct contact with God. Yet underneath the neuro surface lie beliefs and even concrete instructions that can be traced to nineteenth-century hygiene manuals.

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Nutrition: Macronutrient metabolism

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0218 ◽

2020 ◽

pp. 1839-1854

Author(s):

Keith N. Frayn ◽

Rhys D. Evans

Keyword(s):

Amino Acids ◽

Food Intake ◽

Energy Expenditure ◽

Complex Systems ◽

Metabolic Control ◽

Energy Intake ◽

Energy Supply ◽

The Body ◽

Daily Lives ◽

Storage Pools

Food intake is sporadic and, in many cultures, occurs in three daily boluses. At the same time, energy expenditure is continuous and can vary to a large extent independently of the pattern of energy intake, although fixed or predictable demands (e.g. through occupation) means that in most persons food intake and energy expenditure are soon balanced. The body has developed complex systems that direct excess nutrients into storage pools; as they are needed, they also regulate the mobilization of nutrients from these pools. Carbohydrate, lipid, and protein (the latter a source of amino acids) are the three types of energy supply that are stored variably and assimilated from food each day. That we can carry on our daily lives without thinking about whether to store or mobilize fuels, and which to use, attests to the remarkable efficiency and refinement of these systems of metabolic control.

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Imaging and the Human Brain Project: A Review

Methods of Information in Medicine ◽

10.1055/s-0038-1634485 ◽

2002 ◽

Vol 41 (04) ◽

pp. 245-260 ◽

Cited By ~ 16

Author(s):

C. Rosse ◽

J. F. Brinkley

Keyword(s):

Human Brain ◽

Physical Structure ◽

Imaging Informatics ◽

The Body ◽

Human Brain Project ◽

The Us ◽

Physical Organization ◽

The Subject ◽

The Individual ◽

The Brain

Summary Objectives: Survey current work primarily funded by the US Human Brain Project (HBP) that involves substantial use of images. Organize this work around a framework based on the physical organization of the body. Methods: Pointers to individual research efforts were obtained through the HBP home page as well as personal contacts from HBP annual meetings. References from these sources were followed to find closely related work. The individual research efforts were then studied and characterized. Results: The subject of the review is the intersection of neuroinformatics (information about the brain), imaging informatics (information about images), and structural informatics (information about the physical structure of the body). Of the 30 funded projects currently listed on the HBP web site, at least 22 make heavy use of images. These projects are described in terms of broad categories of structural imaging, functional imaging, and image-based brain information systems. Conclusions: Understanding the most complex entity known (the brain) gives rise to many interesting and difficult problems in informatics and computer science. Although much progress has been made by HBP and other neuroinformatics researchers, a great many problems remain that will require substantial informatics research efforts. Thus, the HPB can and should be seen as an excellent driving application area for biomedical informatics research.

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Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00059.2020 ◽

2020 ◽

Author(s):

Eric A. Wilson ◽

Hui Sun ◽

Zhenzhong Cui ◽

Marshal T. Jahnke ◽

Mritunjay Pandey ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Food Intake ◽

Energy Expenditure ◽

Energy Homeostasis ◽

Dorsomedial Hypothalamus ◽

Ambient Temperatures ◽

Brown Adipose ◽

Inhibit Food Intake ◽

Specific Deletion

The G protein subunits Gqα and G11α (Gq/11α) couple receptors to phospholipase C, leading to increased intracellular calcium. In this study we investigated the consequences of Gq/11α deficiency in the dorsomedial hypothalamus (DMH), a critical site for the control of energy homeostasis. Mice with DMH-specific deletion of Gq/11α (DMHGq/11KO) were generated by stereotaxic injection of AAV-Cre-GFP into the DMH of Gqαflox/flox:G11α-/- mice. Compared to control mice that received DMH injection of AAV-GFP, DMHGq/11KO mice developed obesity associated with reduced energy expenditure without significant changes in food intake or physical activity. DMHGq/11KO mice showed no defects in the ability of the melanocortin agonist melanotan II to acutely stimulate energy expenditure or to inhibit food intake. At room temperature (22oC) DMHGq/11KO mice showed reduced sympathetic nervous system activity in brown adipose tissue (BAT) and heart, accompanied with decreased basal BAT Ucp1 gene expression and lower heart rates. These mice were cold intolerant when acutely exposed to cold (6oC for 5 hours) and had decreased cold-stimulated BAT Ucp1 gene expression. DMHGq/11KO mice also failed to adapt to gradually declining ambient temperatures and to develop adipocyte browning in inguinal white adipose tissue although their BAT Ucp1 was proportionally stimulated. Consistent with impaired cold-induced thermogenesis, the onset of obesity in DMHGq/11KO mice was significantly delayed when housed under thermoneutral conditions (30ºC). Thus, our results show that Gqα and G11α in the DMH are required for the control of energy homeostasis by stimulating energy expenditure and thermoregulation.

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Oxytocin Secretion Is Related to Measures of Energy Homeostasis in Young Amenorrheic Athletes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-4136 ◽

2014 ◽

Vol 99 (5) ◽

pp. E881-E885 ◽

Cited By ~ 29

Author(s):

Elizabeth A. Lawson ◽

Kathryn E. Ackerman ◽

Meghan Slattery ◽

Dean A. Marengi ◽

Hannah Clarke ◽

...

Keyword(s):

Body Mass Index ◽

Growth Factor ◽

Food Intake ◽

Energy Expenditure ◽

Energy Homeostasis ◽

Female Athletes ◽

Young Female ◽

Fibroblast Growth Factor 21 ◽

Energy Availability ◽

Fibroblast Growth

Context: Oxytocin has been implicated in the modulation of energy metabolism in animals. Oxytocin knockout mice develop obesity without a change in food intake, suggesting that a lack of oxytocin may reduce metabolic rate. Furthermore, administration of oxytocin centrally reduces food intake in rats, an effect reversed by an oxytocin antagonist, implying that oxytocin may regulate appetite and energy intake. We have previously demonstrated that young female athletes (in a higher energy expenditure state than nonathletes) have low nocturnal oxytocin compared with nonathletes. Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown. Objective: We hypothesized that oxytocin, a signal for energy availability, would be associated with other measures of energy homeostasis in young female athletes. Design and Setting: We performed a cross-sectional study of 45 females, aged 14–21 years [15 amenorrheic athletes (AA), 15 eumenorrheic athletes, and 15 nonathletes] of comparable body mass index. Methods: Dual x-ray absorptiometry was performed to assess body composition. Indirect calorimetry was used to measure resting energy expenditure (REE). Fasting levels of oxytocin, energy homeostasis hormones irisin and fibroblast growth factor-21, and appetite-regulating hormone peptide YY were obtained. Results: In AA, oxytocin secretion was positively correlated with surrogate measures of energy availability, including weight (r = 0.65, P = .009) and body mass index (r = 0.61, P = .016). Furthermore, oxytocin was associated with REE (r = 0.80, P = .0003), independent of lean mass, and with irisin (r = 0.74, P = .002) and fibroblast growth factor-21 (r = 0.58, P = .024). In eumenorrheic athletes, oxytocin was associated with REE (r = 0.59, P = .021), independent of lean mass. In nonathletes, oxytocin secretion was not significantly associated with measures of energy homeostasis. Conclusions: In AA, oxytocin secretion is associated with measures of energy availability and expenditure, suggesting that oxytocin may be involved in regulation of energy balance in energy deficient states. Further studies determining the role of oxytocin in appetite and energy homeostasis in athletes are warranted.

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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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