scholarly journals GEOFFREY HARRIS PRIZE LECTURE 2018: Novel pathways regulating neuroendocrine function, energy homeostasis and metabolism in humans

2019 ◽  
Vol 180 (2) ◽  
pp. R59-R71 ◽  
Author(s):  
Aimilia Eirini Papathanasiou ◽  
Eric Nolen-Doerr ◽  
Olivia M Farr ◽  
Christos S Mantzoros
Keyword(s):  
Energy Homeostasis ◽  
Endocrine System ◽  
Current Evidence ◽  
Energy Reserves ◽  
Neuroendocrine Function ◽  
Available Energy ◽  
Neuroendocrine Response ◽  
Leptin Deficiency ◽  
Molecular Signals ◽  
The Brain

The discovery of leptin, an adipocyte-secreted hormone, set the stage for unraveling the mechanisms dictating energy homeostasis, revealing adipose tissue as an endocrine system that regulates appetite and body weight. Fluctuating leptin levels provide molecular signals to the brain regarding available energy reserves modulating energy homeostasis and neuroendocrine response in states of leptin deficiency and to a lesser extent in hyperleptinemic states. While leptin replacement therapy fails to provide substantial benefit in common obesity, it is an effective treatment for congenital leptin deficiency and states of acquired leptin deficiency such as lipodystrophy. Current evidence suggests that regulation of eating behavior in humans is not limited to homeostatic mechanisms and that the reward, attention, memory and emotion systems are involved, participating in a complex central nervous system network. It is critical to study these systems for the treatment of typical obesity. Although progress has been made, further studies are required to unravel the physiology, pathophysiology and neurobehavioral mechanisms underlying potential treatments for weight-related problems in humans.

Phenotypic abnormalities in macrophages from leptin-deficient, obese mice

1999 ◽  
Vol 276 (2) ◽  
pp. C386-C394 ◽  
Author(s):  
Fung-Yee Janet Lee ◽  
Yunbo Li ◽  
Eun K. Yang ◽  
Shi Qi Yang ◽  
Hui Zhi Lin ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Uncoupling Protein ◽  
Leptin Receptors ◽  
Leptin Deficiency ◽  
Enhancer Binding Protein ◽  
Steady State Levels ◽  
Cox 2 ◽  
The Brain ◽  
General Regulation

Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ obmice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ obmice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-β, an oxidant-sensitive transcription factor, increased expression of interleukin-6 and cyclooxygenase (COX)-2, two C/EBP-β target genes, and increased COX-2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.

scholarly journals The Insulin Regulatory Network in Adult Hippocampus and Pancreatic Endocrine System

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Masanao Machida ◽  
Shin Fujimaki ◽  
Ryo Hidaka ◽  
Makoto Asashima ◽  
Tomoko Kuwabara
Keyword(s):  
Stem Cells ◽  
Learning And Memory ◽  
Energy Homeostasis ◽  
Endocrine System ◽  
Regulatory System ◽  
Diabetic Patients ◽  
Related Factor ◽  
The Central Nervous System ◽  
Lifestyle Disease ◽  
The Brain

There is a very strong correlation between the insulin-mediated regulatory system of the central nervous system and the pancreatic endocrine system. There are many examples of the same transcriptional factors being expressed in both regions in their embryonic development stages. Hormonal signals from the pancreatic islets influence the regulation of energy homeostasis by the brain, and the brain in turn influences the secretions of the islets. Diabetes induces neuronal death in different regions of the brain especially hippocampus, causes alterations on the neuronal circuits and therefore impairs learning and memory, for which the hippocampus is responsible. The hippocampus is a region of the brain where steady neurogenesis continues throughout life. Adult neurogenesis from undifferentiated neural stem cells is greatly decreased in diabetic patients, and as a result their learning and memory functions decline. Might it be possible to reactivate stem cells whose functions have deteriorated and that are present in the tissues in which the lesions occur in diabetes, a lifestyle disease, which plagues modern humans and develops as a result of the behavior of insulin-related factor? In this paper we summarize research in regard to these matters based on examples in recent years.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger
Keyword(s):  
Energy Homeostasis ◽  
Genetic Manipulation ◽  
Heart Function ◽  
Feedback Regulation ◽  
Target Organs ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis ◽  
The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

Natural product-based nanomedicine: Recent advances and issues for the treatment of Alzheimer's disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Choy Ker Woon ◽  
Wong Kah Hui ◽  
Razif Abas ◽  
Muhammad Huzaimi Haron ◽  
Srijit Das ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Medicinal Plants ◽  
Drug Transport ◽  
The Elderly ◽  
Current Evidence ◽  
Alternative Approach ◽  
Progressive Neurodegeneration ◽  
The Brain

: Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and its severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano- sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material’s bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicine-based approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans

2008 ◽  
Vol 294 (1) ◽  
pp. R12-R16 ◽  
Author(s):  
Kerstin M. Oltmanns ◽  
Uwe H. Melchert ◽  
Harald G. Scholand-Engler ◽  
Maria C. Howitz ◽  
Bernd Schultes ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Underlying Mechanism ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
Energy Status ◽  
High Energy Phosphate ◽  
Available Energy ◽  
Healthy Humans ◽  
High Energy Phosphate Metabolism ◽  
The Brain

The brain regulates all metabolic processes within the organism, and therefore, its energy supply is preserved even during fasting. However, the underlying mechanism is unknown. Here, it is shown, using 31P-magnetic resonance spectroscopy that during short periods of hypoglycemia and hyperglycemia, the brain can rapidly increase its high-energy phosphate content, whereas there is no change in skeletal muscle. We investigated the key metabolites of high-energy phosphate metabolism as rapidly available energy stores by 31P MRS in brain and skeletal muscle of 17 healthy men. Measurements were performed at baseline and during dextrose or insulin-induced hyperglycemia and hypoglycemia. During hyperglycemia, phosphocreatine (PCr) concentrations increased significantly in the brain ( P = 0.013), while there was a similar trend in the hypopglycemic condition ( P = 0.055). Skeletal muscle content remained constant in both conditions ( P > 0.1). ANOVA analyses comparing changes from baseline to the respective glycemic plateau in brain (up to +15%) vs. muscle (up to −4%) revealed clear divergent effects in both conditions ( P < 0.05). These effects were reflected by PCr/Pi ratio ( P < 0.05). Total ATP concentrations revealed the observed divergency only during hyperglycemia ( P = 0.018). These data suggest that the brain, in contrast to peripheral organs, can activate some specific mechanisms to modulate its energy status during variations in glucose supply. A disturbance of these mechanisms may have far-reaching implications for metabolic dysregulation associated with obesity or diabetes mellitus.

scholarly journals Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

2003 ◽  
Vol 149 (2) ◽  
pp. 79-90 ◽  
Author(s):  
ML Raffin-Sanson ◽  
Y de Keyzer ◽  
X Bertagna
Keyword(s):  
Anterior Pituitary ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Single Gene ◽  
Local Production ◽  
Biological Functions ◽  
Multiple Functions ◽  
Pathological Conditions ◽  
Recent Developments ◽  
The Brain

Proopiomelanocortin (POMC) is the polypeptide precursor of ACTH. First discovered in anterior pituitary corticotroph cells, it has more recently been revealed to have many other physiological aspects. The fine molecular mechanisms of ACTH biosynthesis show that ACTH is but one piece of a puzzle which contains many other peptides. Present in various tIssues, among which are pituitary, hypothalamus, central nervous system and skin, POMC undergoes extensive post-translational processing. This processing is tIssue-specific and generates, depending on the case, various sets of peptides involved in completely diverse biological functions. POMC expressed in corticotroph cells of the pituitary is necessary for adrenal function. Recent developments have shown that POMC-expressing neurons in the brain play a major role in the control of pain and energy homeostasis. Local production of POMC-derived peptides in skin may influence melanogenesis. A still unknown function in the placenta is likely.POMC has become a paradigmatic polypeptide precursor model illustrating the variable roles of a single gene and its various products in different localities.

scholarly journals Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
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.

scholarly journals Human Creativity and Consciousness: Unintended Consequences of the Brain’s Extraordinary Energy Efficiency?

2020 ◽  
Author(s):  
Tim Palmer
Keyword(s):  
Energy Efficiency ◽  
Human Brain ◽  
Quantum Physics ◽  
Unintended Consequences ◽  
Large Network ◽  
Active Neuron ◽  
Available Energy ◽  
Human Creativity ◽  
The One ◽  
The Brain

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain&rsquo;s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman&rsquo;s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons. As such, the amount of energy per active neuron is so small that the operation of such neurons is susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a small enough subset of neurons to guarantee a deterministic operation. An illustration of how this synergy can lead to creativity with implications for computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between our memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks. As with the brain&rsquo;s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears so counter-intuitive.

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