scholarly journals Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

2020 ◽  
Vol 21 (5) ◽  
pp. 1554 ◽  
Author(s):  
Nicola Forte ◽  
Alba Clara Fernández-Rilo ◽  
Letizia Palomba ◽  
Vincenzo Di Marzo ◽  
Luigia Cristino
Keyword(s):  
Intestinal Microbiota ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Hypothalamic Area ◽  
Peripheral Tissues ◽  
Regulatory Circuits ◽  
Bidirectional Communication ◽  
Factor Α ◽  
Fat Diets ◽  
The Brain

The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

The role of amylin in the control of energy homeostasis

2010 ◽  
Vol 298 (6) ◽  
pp. R1475-R1484 ◽  
Author(s):  
Thomas A. Lutz
Keyword(s):  
Energy Homeostasis ◽  
Area Postrema ◽  
Body Weight Gain ◽  
Direct Action ◽  
Central Administration ◽  
Experimental Conditions ◽  
Hypothalamic Area ◽  
Chronic Infusion ◽  
The Brain

Amylin is an important player in the control of nutrient fluxes. Amylin reduces eating via a meal size effect by promoting meal-ending satiation. This effect seems to depend on a direct action in the area postrema (AP), which is an area rich in amylin receptors. Subsequent to the activation of AP neurons, the neural signal is conveyed to the forebrain via relays involving the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (lPBN) to the lateral hypothalamic area (LHA) and other hypothalamic nuclei. While the NTS and lPBN seem to be necessary for amylin's eating inhibitory effect, the role of the LHA has not yet been fully investigated. Amylin may also act as an adiposity signal. Plasma levels of amylin are higher in obese individuals, and chronic infusion of amylin into the brain reduces body weight gain and adiposity; chronic infusion of an amylin receptor antagonist into the brain increases body adiposity. Amylin increases energy expenditure in rats; this effect occurs under various experimental conditions after peripheral and central administration. Together, these animal data, but also clinical data in humans, indicate that amylin is a promising candidate for the treatment of obesity; effects are most pronounced when amylin is combined with leptin. Finally, recent findings indicate that amylin acts as a neurotrophic factor in specific brain stem areas. Whether this effect may be relevant under physiological conditions requires further studies.

scholarly journals Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding

Science ◽  
2019 ◽  
Vol 364 (6447) ◽  
pp. 1271-1274 ◽  
Author(s):  
Mark A. Rossi ◽  
Marcus L. Basiri ◽  
Jenna A. McHenry ◽  
Oksana Kosyk ◽  
James M. Otis ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Health Concern ◽  
Hypothalamic Area ◽  
Obesity Epidemic ◽  
Glutamatergic Neurons ◽  
Two Photon ◽  
Lateral Hypothalamic ◽  
The Brain ◽  
Transcriptional State

The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)—a highly conserved brain region that orchestrates feeding—in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.

The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain

2020 ◽  
Vol 318 (5) ◽  
pp. C818-C830 ◽  
Author(s):  
Kyle S. Martin ◽  
Michele Azzolini ◽  
Jorge Lira Ruas
Keyword(s):  
Skeletal Muscle ◽  
Immune System ◽  
Energy Homeostasis ◽  
Biological Activities ◽  
Tissue Expression ◽  
Kynurenine Pathway ◽  
Bioactive Metabolites ◽  
Peripheral Tissues ◽  
Exercise Induced ◽  
The Brain

Tryptophan catabolism through the kynurenine pathway generates a variety of bioactive metabolites. Physical exercise can modulate kynurenine pathway metabolism in skeletal muscle and thus change the concentrations of select compounds in peripheral tissues and in the central nervous system. Here we review recent advances in our understanding of how exercise alters tryptophan-kynurenine metabolism in muscle and its subsequent local and distal effects. We propose that the effects of kynurenine pathway metabolites on skeletal muscle, adipose tissue, immune system, and the brain suggest that some of these compounds could qualify as exercise-induced myokines. Indeed, some of the more recently discovered biological activities for kynurenines include many of the best-known benefits of exercise: improved energy homeostasis, promotion of an anti-inflammatory environment, and neuroprotection. Finally, by considering the tissue expression of the different membrane and cytosolic receptors for kynurenines, we discuss known and potential biological activities for these tryptophan metabolites.

scholarly journals 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

2016 ◽  
Vol 56 (4) ◽  
pp. T157-T174 ◽  
Author(s):  
Erica J P Anderson ◽  
Isin Çakir ◽  
Sheridan J Carrington ◽  
Roger D Cone ◽  
Masoud Ghamari-Langroudi ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Critical Role ◽  
Melanocortin System ◽  
Melanocyte Stimulating Hormone ◽  
Syndromic Obesity ◽  
Melanocortin Peptides ◽  
History Of ◽  
Glucocorticoid Production ◽  
The Brain ◽  
Biological Actions

The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2–5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.

scholarly journals The Circadian Clock and Viral Infections

2020 ◽  
pp. 074873042096776
Author(s):  
Helene Borrmann ◽  
Jane A McKeating ◽  
Xiaodong Zhuang
Keyword(s):  
Circadian Clock ◽  
Clinical Evidence ◽  
Viral Infections ◽  
Peripheral Tissues ◽  
Antiviral Therapies ◽  
Regulatory Circuits ◽  
Fertile Ground ◽  
Central Clock ◽  
And Behavior ◽  
The Brain

The circadian clock controls several aspects of mammalian physiology and orchestrates the daily oscillations of biological processes and behavior. Our circadian rhythms are driven by an endogenous central clock in the brain that synchronizes with clocks in peripheral tissues, thereby regulating our immune system and the severity of infections. These rhythms affect the pharmacokinetics and efficacy of therapeutic agents and vaccines. The core circadian regulatory circuits and clock-regulated host pathways provide fertile ground to identify novel antiviral therapies. An increased understanding of the role circadian systems play in regulating virus infection and the host response to the virus will inform our clinical management of these diseases. This review provides an overview of the experimental and clinical evidence reporting on the interplay between the circadian clock and viral infections, highlighting the importance of virus-clock research.

scholarly journals Neuronal Control of Bone Remodeling

2017 ◽  
Vol 45 (7) ◽  
pp. 894-903 ◽  
Author(s):  
Alexander Corr ◽  
James Smith ◽  
Paul Baldock
Keyword(s):  
Neural Control ◽  
Energy Homeostasis ◽  
Cell Activity ◽  
Bone Cell ◽  
Central Regulation ◽  
Peripheral Tissues ◽  
Regulatory Pathways ◽  
Organ Systems ◽  
Paradigm Shifting ◽  
The Brain

Although the brain is well established as a master regulator of homeostasis in peripheral tissues, central regulation of bone mass represents a novel and rapidly expanding field of study. This review examines the current understanding of central regulation of the skeleton, exploring several of the key pathways connecting brain to bone and their implications both in mice and the clinical setting. Our understanding of central bone regulation has largely progressed through examination of skeletal responses downstream of nutrient regulatory pathways in the hypothalamus. Mutations and modulation of these pathways, in cases such as leptin deficiency, induce marked bone phenotypes, which have provided vital insights into central bone regulation. These studies have identified several central neuropeptide pathways that stimulate well-defined changes in bone cell activity in response to changes in energy homeostasis. In addition, this work has highlighted the endocrine nature of the skeleton, revealing a complex cross talk that directly regulates other organ systems. Our laboratory has studied bone-active neuropeptide pathways and defined osteoblast-based actions that recapitulate central pathways linking bone, fat, and glucose homeostasis. Studies of neural control of bone have produced paradigm-shifting changes in our understanding of the skeleton and its relationship with the wider array of organ systems.

scholarly journals Sulfide catabolism ameliorates hypoxic brain injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eizo Marutani ◽  
Masanobu Morita ◽  
Shuichi Hirai ◽  
Shinichi Kai ◽  
Robert M. H. Grange ◽  
...  
Keyword(s):  
Brain Injury ◽  
Mitochondrial Respiration ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Ground Squirrels ◽  
Mammalian Brain ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Sulfide:Quinone Oxidoreductase ◽  
The Brain

AbstractThe mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.

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 Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

2020 ◽  
Vol 57 (12) ◽  
pp. 5026-5043 ◽  
Author(s):  
Shan Liu ◽  
Jiguo Gao ◽  
Mingqin Zhu ◽  
Kangding Liu ◽  
Hong-Liang Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Gut Dysbiosis ◽  
Bidirectional Communication ◽  
Significant Research ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Brain Homeostasis ◽  
Gut Microbiota Composition

Abstract Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

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