scholarly journals Interleukin-6 Expression by Hypothalamic Microglia in Multiple Inflammatory Contexts: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Vanessa C. D. Bobbo ◽  
Carlos P. Jara ◽  
Natália F. Mendes ◽  
Joseane Morari ◽  
Lício A. Velloso ◽  
...  
Keyword(s):  
Systematic Review ◽  
Interleukin 6 ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Positive Energy ◽  
Anatomical Site ◽  
Control Food ◽  
Control Food Intake

Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been induced. Specific neurons of the hypothalamus provide important signals to control food intake and energy expenditure. In individuals with obesity, a microglia-dependent inflammatory response damages the neural circuits responsible for maintaining whole-body energy homeostasis, resulting in a positive energy balance. However, little is known about the role of IL-6 in the regulation of hypothalamic microglia. In this systematic review, we asked what types of conditions and stimuli could modulate microglial IL-6 expression in murine model. We searched the PubMed and Web of Science databases and analyzed 13 articles that evaluated diverse contexts and study models focused on IL-6 expression and microglia activation, including the effects of stress, hypoxia, infection, neonatal overfeeding and nicotine exposure, lipopolysaccharide stimulus, hormones, exercise protocols, and aging. The results presented in this review emphasized the role of “injury-like” stimuli, under which IL-6 acts as a proinflammatory cytokine, concomitant with marked microglial activation, which drive hypothalamic neuroinflammation. Emerging evidence indicates an important correlation of basal IL-6 levels and microglial function with the maintenance of hypothalamic homeostasis. Advances in our understanding of these different contexts will lead to the development of more specific pharmacological approaches for the management of acute and chronic conditions, like obesity and metabolic diseases, without disturbing the homeostatic functions of IL-6 and microglia in the hypothalamus.

scholarly journals Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

2021 ◽  
Author(s):  
Verónica Hurtado-Carneiro ◽  
Ana Pérez-García ◽  
Elvira Álvarez ◽  
Carmen Sanz
Keyword(s):  
Type 2 Diabetes ◽  
Nutrient Availability ◽  
Energy Demand ◽  
Metabolic Response ◽  
Whole Body ◽  
Key Factor ◽  
Control Food ◽  
Control Food Intake

Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

scholarly journals Allicin regulates energy homeostasis through brown adipose tissue

2019 ◽  
Author(s):  
Chuanhai Zhang ◽  
Xiaoyun He ◽  
Yao Sheng ◽  
Jia Xu ◽  
Cui Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Promising Therapeutic Approach ◽  
Treatment Of Obesity

AbstractBackground/objectives:Disorder of energy homeostasis can lead to a variety of metabolic diseases, especially obesity. Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a main bioactive ingredient in garlic, has multiple biology and pharmacological function. However, the role of Allicin, in the regulation of metabolic organ, especially the role of activation of BAT, has not been well studied. Here, we analyzed the role of Allicin in whole-body metabolism and the activation of BAT.Results:Allicin had a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in diet-introduced obesity (DIO) mice. Then we find that Allicin can strongly activate brown adipose tissue (BAT). The activation of brown adipocyte treated with Allicin was also confirmed in mouse primary brown adipocytes.Conclusion:Allicin can ameliorate obesity through activating brown adipose tissue. Our findings provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

The AMP-activated protein kinase: more than an energy sensor

2007 ◽  
Vol 43 ◽  
pp. 121-138 ◽  
Author(s):  
Louis Hue ◽  
Mark H. Rider
Keyword(s):  
Protein Kinase ◽  
Metabolic Diseases ◽  
Cellular Level ◽  
Whole Body ◽  
Energy Status ◽  
Cellular Energy ◽  
The Metabolic Syndrome ◽  
Control Food ◽  
Control Food Intake ◽  
Amp Activated Protein Kinase

The AMPK (AMP-activated protein kinase) is a highly conserved eukaryotic protein serine/threonine kinase. It mediates a nutrient signalling pathway that senses cellular energy status and was appropriately called the fuel gauge of the cell. At the cellular level, AMPK controls energy homoeostasis by switching on catabolic ATP-generating pathways, while switching off anabolic ATP-consuming processes. Its effect on energy balance extends to whole-body energy homoeostasis, because, in the hypothalamus, it integrates nutritional and hormonal signals that control food intake and body weight. The interest in AMPK also stems from the demonstration of its insulin-independent stimulation of glucose transport in skeletal muscle during exercise. Moreover, the potential importance of AMPK in metabolic diseases is supported by the notion that AMPK mediates the anti-diabetic action of biguanides and thiazolidinediones and that it might be involved in the metabolic syndrome. Finally, the more recent demonstration that AMPK activation could occur independently of changes in cellular energy status, suggests that AMPK action extends to the control of non-metabolic functions.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

scholarly journals The Function of Gastrointestinal Hormones in Obesity—Implications for the Regulation of Energy Intake

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1839
Author(s):  
Mona Farhadipour ◽  
Inge Depoortere
Keyword(s):  
Energy Homeostasis ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Enteroendocrine Cells ◽  
Hormone Balance ◽  
Gut Hormone ◽  
Control Food ◽  
Induce Weight Loss ◽  
Novel Strategy ◽  
Control Food Intake

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity.

scholarly journals Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation

2019 ◽  
Vol 74 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Dan Yang ◽  
Yifan Yang ◽  
Yanlin Li ◽  
Rui Han
Keyword(s):  
Type 2 Diabetes ◽  
Exercise Therapy ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Mechanism Study ◽  
Physiological Mechanisms ◽  
Glycolipid Metabolism ◽  
Randomized Controlled Studies

Background: Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. Summary: Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. Key Messages: More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.

scholarly journals Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

2020 ◽  
Vol 375 (1793) ◽  
pp. 20190135 ◽  
Author(s):  
Naresh C. Bal ◽  
Muthu Periasamy
Keyword(s):  
Energy Homeostasis ◽  
Atp Hydrolysis ◽  
Calcium Atpase ◽  
Whole Body ◽  
Signalling Molecule ◽  
Brown Adipose ◽  
Pump Activity ◽  
Body Energy ◽  
Shivering Thermogenesis

Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca 2+ -cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca 2+ transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

scholarly journals Cellular Distribution, Regulated Expression, and Functional Role of the Anorexigenic Peptide, NUCB2/Nesfatin-1, in the Testis

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1959-1971 ◽  
Author(s):  
D. García-Galiano ◽  
R. Pineda ◽  
T. Ilhan ◽  
J. M. Castellano ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Functional Role ◽  
Energy Homeostasis ◽  
Ex Vivo ◽  
Whole Body ◽  
Mrna Levels ◽  
Gonadal Function ◽  
Human Choriogonadotropin ◽  
Puberty Onset

Nesfatin-1, product of the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as anorectic hypothalamic neuropeptide, acting in a leptin-independent manner. In addition to its central role in the control of energy homeostasis, evidence has mounted recently that nesfatin-1 is also produced in peripheral metabolic tissues, such as pancreas, adipose, and gut. Moreover, nesfatin-1 has been shown to participate in the control of body functions gated by whole-body energy homeostasis, including puberty onset. Yet, whether, as is the case for other metabolic neuropeptides, NUCB2/nesfatin-1 participates in the direct control of gonadal function remains unexplored. We document here for the first time the expression of NUCB2 mRNA in rat, mouse, and human testes, where NUCB2/nesfatin-1 protein was identified in interstitial mature Leydig cells. Yet in rats, NUCB2/nesfatin-1 became expressed in Sertoli cells upon Leydig cell elimination and was also detected in Leydig cell progenitors. Although NUCB2 mRNA levels did not overtly change in rat testis during pubertal maturation and after short-term fasting, NUCB2/nesfatin-1 content significantly increased along the puberty-to-adult transition and was markedly suppressed after fasting. In addition, testicular NUCB2/nesfatin-1 expression was up-regulated by pituitary LH, because hypophysectomy decreased, whereas human choriogonadotropin (super-agonist of LH receptors) replacement enhanced, NUCB2/nesfatin-1 mRNA and peptide levels. Finally, nesfatin-1 increased human choriogonadotropin-stimulated testosterone secretion by rat testicular explants ex vivo. Our data are the first to disclose the presence and functional role of NUCB2/nesfatin-1 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues as well as by Leydig cell-derived factors. Our observations expand the reproductive dimension of nesfatin-1, which may operate directly at the testicular level to link energy homeostasis, puberty onset, and gonadal function.

scholarly journals Perspective: Mitochondria-ER Contacts in Metabolic Cellular Stress Assessed by Microscopy

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Alessandra Stacchiotti ◽  
Gaia Favero ◽  
Antonio Lavazza ◽  
Raquel Garcia-Gomez ◽  
Maria Monsalve ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Calcium Ions ◽  
Metabolic Diseases ◽  
Cellular Stress ◽  
Pivotal Role ◽  
Whole Body ◽  
Oxygen Species ◽  
Whole Body Metabolism

The interplay of mitochondria with the endoplasmic reticulum and their connections, called mitochondria-ER contacts (MERCs) or mitochondria-associated ER membranes (MAMs), are crucial hubs in cellular stress. These sites are essential for the passage of calcium ions, reactive oxygen species delivery, the sorting of lipids in whole-body metabolism. In this perspective article, we focus on microscopic evidences of the pivotal role of MERCs/MAMs and their changes in metabolic diseases, like obesity, diabetes, and neurodegeneration.

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