scholarly journals Chemerin: a multifaceted adipokine involved in metabolic disorders

2018 ◽  
Vol 238 (2) ◽  
pp. R79-R94 ◽  
Author(s):  
Gisela Helfer ◽  
Qing-Feng Wu
Keyword(s):  
Food Intake ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Treatment Strategies ◽  
Public Health Problem ◽  
Global Public Health ◽  
Loss Of Function ◽  
Peripheral Tissues ◽  
Underlying Mechanisms

Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with BMI and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In general, chemerin is upregulated in obese and diabetic animals. Previous studies by gain or loss of function show an association of chemerin with adipogenesis, glucose homeostasis, food intake and body weight. In the brain, the hypothalamus integrates peripheral afferent signals including adipokines to regulate appetite and energy homeostasis. Chemerin increases food intake in seasonal animals by acting on hypothalamic stem cells, the tanycytes. In peripheral tissues, chemerin increases cell expansion, inflammation and angiogenesis in adipose tissue, collectively resulting in adiposity. While chemerin signalling enhances insulin secretion from pancreatic islets, contradictory results have been reported on how chemerin links to obesity and insulin resistance. Given the association of chemerin with obesity comorbidities in humans, advances in translational research targeting chemerin are expected to mitigate metabolic disorders. Together, the exciting findings gathered in the last decade clearly indicate a crucial multifaceted role for chemerin in the regulation of energy balance, making it a promising candidate for urgently needed pharmacological treatment strategies for obesity.

scholarly journals Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

2020 ◽  
Vol 21 (7) ◽  
pp. 2568
Author(s):  
Ujendra Kumar ◽  
Sneha Singh
Keyword(s):  
Food Intake ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Eating Behaviour ◽  
Peripheral Tissues ◽  
Complex Process ◽  
The Many ◽  
The One ◽  
Food Seeking

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

scholarly journals Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance

2018 ◽  
Vol 19 (11) ◽  
pp. 3552 ◽  
Author(s):  
Baile Wang ◽  
Kenneth Cheng
Keyword(s):  
Energy Balance ◽  
Hormonal Regulation ◽  
Energy Homeostasis ◽  
Adenosine Monophosphate ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Adaptive Thermogenesis ◽  
Increase Food Intake ◽  
Regulatory Effects ◽  
Underlying Mechanisms

As a cellular energy sensor and regulator, adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a pivotal role in the regulation of energy homeostasis in both the central nervous system (CNS) and peripheral organs. Activation of hypothalamic AMPK maintains energy balance by inducing appetite to increase food intake and diminishing adaptive thermogenesis in adipose tissues to reduce energy expenditure in response to food deprivation. Numerous metabolic hormones, such as leptin, adiponectin, ghrelin and insulin, exert their energy regulatory effects through hypothalamic AMPK via integration with the neural circuits. Although activation of AMPK in peripheral tissues is able to promote fatty acid oxidation and insulin sensitivity, its chronic activation in the hypothalamus causes obesity by inducing hyperphagia in both humans and rodents. In this review, we discuss the role of hypothalamic AMPK in mediating hormonal regulation of feeding and adaptive thermogenesis, and summarize the diverse underlying mechanisms by which central AMPK maintains energy homeostasis.

scholarly journals Structure–Activity Relationships of the Tetrapeptide Ac-His-Arg-(pI)DPhe-Tic-NH2 at the Mouse Melanocortin Receptors: Modification at the (pI)DPhe Position Leads to mMC3R Versus mMC4R Selective Ligands

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1463
Author(s):  
Katherine N. Schlasner ◽  
Mark D. Ericson ◽  
Skye R. Doering ◽  
Katie T. Freeman ◽  
Mary Weinrich ◽  
...  
Keyword(s):  
Food Intake ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Biological Pathways ◽  
Melanocortin Receptors ◽  
Lead Compounds ◽  
Structure Activity ◽  
Selective Ligands ◽  
Selective Agonists

The five melanocortin receptors (MC1R–MC5R) are involved in numerous biological pathways, including steroidogenesis, pigmentation, and food intake. In particular, MC3R and MC4R knockout mice suggest that the MC3R and MC4R regulate energy homeostasis in a non-redundant manner. While MC4R-selective agonists have been utilized as appetite modulating agents, the lack of MC3R-selective agonists has impeded progress in modulating this receptor in vivo. In this study, the (pI)DPhe position of the tetrapeptide Ac-His-Arg-(pI)DPhe-Tic-NH2 (an MC3R agonist/MC4R antagonist ligand) was investigated with a library of 12 compounds. The compounds in this library were found to have higher agonist efficacy and potency at the mouse (m) MC3R compared to the MC4R, indicating that the Arg-DPhe motif preferentially activates the mMC3R over the mMC4R. This observation may be used in the design of new MC3R-selective ligands, leading to novel probe and therapeutic lead compounds that will be useful for treating metabolic disorders.

scholarly journals Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chongru Zhao ◽  
Weijie Hu ◽  
Yi Xu ◽  
Dawei Wang ◽  
Yichen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Energy Homeostasis ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Novel Treatment ◽  
Common Cancer ◽  
Prevalence Of Obesity ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms ◽  
The Impact

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

Rhodiola and salidroside in the treatment of metabolic disorders

2019 ◽  
Vol 19 (19) ◽  
pp. 1611-1626 ◽  
Author(s):  
Xiang-Li Bai ◽  
Xiu-Ling Deng ◽  
Guang-Jie Wu ◽  
Wen-Jing Li ◽  
Si Jin
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Ampk Signaling ◽  
Beneficial Effects

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.

scholarly journals Quantitative approaches to energy and glucose homeostasis: machine learning and modelling for precision understanding and prediction

2018 ◽  
Vol 15 (138) ◽  
pp. 20170736 ◽  
Author(s):  
Thomas McGrath ◽  
Kevin G. Murphy ◽  
Nick S. Jones
Keyword(s):  
Machine Learning ◽  
Energy Homeostasis ◽  
Public Health Problem ◽  
Predictive Ability ◽  
Machine Learning Techniques ◽  
Global Public Health ◽  
Diverse Range ◽  
Physiological Models ◽  
Learning Techniques ◽  
New Treatments

Obesity is a major global public health problem. Understanding how energy homeostasis is regulated, and can become dysregulated, is crucial for developing new treatments for obesity. Detailed recording of individual behaviour and new imaging modalities offer the prospect of medically relevant models of energy homeostasis that are both understandable and individually predictive. The profusion of data from these sources has led to an interest in applying machine learning techniques to gain insight from these large, relatively unstructured datasets. We review both physiological models and machine learning results across a diverse range of applications in energy homeostasis, and highlight how modelling and machine learning can work together to improve predictive ability. We collect quantitative details in a comprehensive mathematical supplement. We also discuss the prospects of forecasting homeostatic behaviour and stress the importance of characterizing stochasticity within and between individuals in order to provide practical, tailored forecasts and guidance to combat the spread of obesity.

scholarly journals Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis in Npr1 haplotype male mice

2017 ◽  
Vol 313 (3) ◽  
pp. F781-F795 ◽  
Author(s):  
Prerna Kumar ◽  
Venkateswara R. Gogulamudi ◽  
Ramu Periasamy ◽  
Giri Raghavaraju ◽  
Umadevi Subramanian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Critical Role ◽  
Treatment Strategies ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Renal Inflammation ◽  
Dna Binding Activity ◽  
Underlying Mechanisms ◽  
Molecular Therapeutic ◽  
Haplotype 1

Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) plays a critical role in the regulation of blood pressure and fluid volume homeostasis. Mice lacking functional Npr1 (coding for GC-A/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear. The objective of the present study was to determine the physiological efficacy and impact of all- trans-retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in Npr1 gene-disrupted haplotype (1-copy; +/−) mice (50% expression levels of NPRA). Both ATRA and NaBu, either alone or in combination, decreased the elevated levels of renal proinflammatory and profibrotic cytokines and lowered blood pressure in Npr1+/− mice compared with untreated controls. The treatment with ATRA-NaBu facilitated the dissociation of histone deacetylase (HDAC) 1 and 2 from signal transducer and activator of transcription 1 (STAT1) and enhanced its acetylation in the kidneys of Npr1+/− mice. The acetylated STAT1 formed a complex with nuclear factor-κB (NF-κB) p65, thereby inhibiting its DNA-binding activity and downstream proinflammatory and profibrotic signaling cascades. The present results demonstrate that the treatment of the haplotype Npr1+/− mice with ATRA-NaBu significantly lowered blood pressure and reduced the renal inflammation and fibrosis involving the interactive roles of HDAC, NF-κB (p65), and STAT1. The current findings will help in developing the molecular therapeutic targets and new treatment strategies for hypertension and renal dysfunction in humans.

scholarly journals Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis

2016 ◽  
Vol 310 (11) ◽  
pp. E994-E1002 ◽  
Author(s):  
Fang Hu ◽  
Yong Xu ◽  
Feng Liu
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Energy Status ◽  
Energy Balancing ◽  
Functional Roles ◽  
Neuronal Populations ◽  
Underlying Mechanisms ◽  
Mtor Complex 1 ◽  
Hormone Signals

Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of “energy balancing” hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes.

scholarly journals Repetitive Transcranial Magnetic Stimulation Target Location Methods for Depression

2021 ◽  
Vol 15 ◽  
Author(s):  
Min Zhang ◽  
Runhua Wang ◽  
Xin Luo ◽  
Si Zhang ◽  
Xiaomei Zhong ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Target Location ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Treatment Strategies ◽  
Public Health Problem ◽  
Global Public Health ◽  
Non Invasive ◽  
Dorsolateral Prefrontal ◽  
Location Methods

Major depressive disorder (MDD) is a substantial global public health problem in need of novel and effective treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and promising treatment for depression that has been approved by the U.S. Food and Drug Administration (FDA). However, the methodological weaknesses of existing work impairs the universal clinical use of rTMS. The variation of stimulated targets across the dorsolateral prefrontal cortex may account for most of the heterogeneity in the efficacy of rTMS. Many rTMS target location methods for MDD have been developed in recent decades. This review was conducted to assess this emerging field and to improve treatment outcomes in clinical practice.

scholarly journals Recent advances in understanding the role of leptin in energy homeostasis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 451
Author(s):  
Heike Münzberg ◽  
Prachi Singh ◽  
Steven B. Heymsfield ◽  
Sangho Yu ◽  
Christopher D. Morrison
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Early Data ◽  
Dynamic Changes ◽  
Leptin Signaling ◽  
Future Studies ◽  
Physiological Adaptations

The hormone leptin plays a critical role in energy homeostasis, although our overall understanding of acutely changing leptin levels still needs improvement. Several developments allow a fresh look at recent and early data on leptin action. This review highlights select recent publications that are relevant for understanding the role played by dynamic changes in circulating leptin levels. We further discuss the relevance for our current understanding of leptin signaling in central neuronal feeding and energy expenditure circuits and highlight cohesive and discrepant findings that need to be addressed in future studies to understand how leptin couples with physiological adaptations of food intake and energy expenditure.

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