β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Sai P. Pydi ◽  
Luiz F. Barella ◽  
Lu Zhu ◽  
Jaroslawna Meister ◽  
Mario Rossi ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Cell Types ◽  
Mutant Mice ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Cytoplasmic Proteins ◽  
New Findings ◽  
Novel Drugs ◽  
G Protein Coupled

β-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein–coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two β-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed β-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both β-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that β-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and pathophysiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Two β-Arrestins Regulate Distinct Metabolic Processes: Studies with Novel Mutant Mouse Models

2022 ◽  
Vol 23 (1) ◽  
pp. 495
Author(s):  
Jürgen Wess
Keyword(s):  
Energy Homeostasis ◽  
Mutant Mouse ◽  
Cultured Cells ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Mutant Mice ◽  
Signaling Proteins ◽  
High Degree ◽  
G Protein Coupled

The two β-arrestins (β-arrestin-1 and -2; alternative names: arrestin-2 and -3, respectively) are well known for their ability to inhibit signaling via G protein-coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. Although the two proteins share a high degree of sequence and structural homology, early studies with cultured cells indicated that β-arrestin-1 and -2 are not functionally redundant. Recently, the in vivo metabolic roles of the two β-arrestins have been studied using mutant mice selectively lacking either β-arrestin-1 or -2 in cell types that are of particular relevance for regulating glucose and energy homeostasis. These studies demonstrated that the β-arrestin-1 and -2 mutant mice displayed distinct metabolic phenotypes in vivo, providing further evidence for the functional heterogeneity of these two highly versatile signaling proteins.

Roles of Endocannabinoids and Endocannabinoid-like Molecules in Energy Homeostasis and Metabolic Regulation: A Nutritional Perspective

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
S.M. Khaledur Rahman ◽  
Toru Uyama ◽  
Zahir Hussain ◽  
Natsuo Ueda
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Cannabinoid Receptors ◽  
Biological Activities ◽  
Endocannabinoid System ◽  
Annual Review ◽  
Publication Date ◽  
Treatment And Prevention ◽  
G Protein Coupled

The endocannabinoid system is involved in signal transduction in mammals. It comprises principally G protein-coupled cannabinoid receptors and their endogenous agonists, called endocannabinoids, as well as the enzymes and transporters responsible for the metabolism of endocannabinoids. Two arachidonic acid–containing lipid molecules, arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol, function as endocannabinoids. N-acylethanolamines and monoacylglycerols, in which the arachidonic acid chain is replaced with a saturated or monounsaturated fatty acid, are not directly involved in the endocannabinoid system but exhibit agonistic activities for other receptors. These endocannabinoid-like molecules include palmitoylethanolamide, oleoylethanolamide (OEA), and 2-oleoylglycerol. Endocannabinoids stimulate feeding behavior and the anabolism of lipids and glucose, while OEA suppresses appetite. Both central and peripheral systems are included in these nutritional and metabolic contexts. Therefore, they have potential in the treatment and prevention of obesity. We outline the structure, metabolism, and biological activities of endocannabinoids and related molecules, and focus on their involvement in energy homeostasis and metabolic regulation. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Benjamin J. Moss ◽  
Stefan W. Ryter ◽  
Ivan O. Rosas
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Alveolar Epithelial Cell ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Metabolic Dysfunction ◽  
Epithelial Repair

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves a complex interplay of cell types and signaling pathways. Recurrent alveolar epithelial cell (AEC) injury may occur in the context of predisposing factors (e.g., genetic, environmental, epigenetic, immunologic, and gerontologic), leading to metabolic dysfunction, senescence, aberrant epithelial cell activation, and dysregulated epithelial repair. The dysregulated epithelial cell interacts with mesenchymal, immune, and endothelial cells via multiple signaling mechanisms to trigger fibroblast and myofibroblast activation. Recent single-cell RNA sequencing studies of IPF lungs support the epithelial injury model. These studies have uncovered a novel type of AEC with characteristics of an aberrant basal cell, which may disrupt normal epithelial repair and propagate a profibrotic phenotype. Here, we review the pathogenesis of IPF in the context of novel bioinformatics tools as strategies to discover pathways of disease, cell-specific mechanisms, and cell-cell interactions that propagate the profibrotic niche. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Integrated Patterning Programs During Drosophila Development Generate the Diversity of Neurons and Control Their Mature Properties

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Anthony M. Rossi ◽  
Shadi Jafari ◽  
Claude Desplan
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Temporal Patterning ◽  
Long Time ◽  
Neuronal Types ◽  
And Control

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Uterine Excitability and Ion Channels and Their Changes with Gestation and Hormonal Environment

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Susan Wray ◽  
Sarah Arrowsmith
Keyword(s):  
Ion Channels ◽  
Inward Rectifier ◽  
Cation Channels ◽  
Annual Review ◽  
Publication Date ◽  
K Channels ◽  
Voltage Gated ◽  
New Findings ◽  
Voltage Dependent ◽  
Pore Domain

We address advances in the understanding of myometrial physiology, focusing on excitation and the effects of gestation on ion channels and their relevance to labor. This review moves through pioneering studies to exciting new findings. We begin with the myometrium and its myocytes and describe how excitation might initiate and spread in this myogenic smooth muscle. We then review each of the ion channels in the myometrium: L- and T-type Ca2+ channels, KATP (Kir6) channels, voltage-dependent K channels (Kv4, Kv7, and Kv11), twin-pore domain K channels (TASK, TREK), inward rectifier Kir7.1, Ca2+-activated K+ channels with large (KCNMA1, Slo1), small (KCNN1–3), and intermediate (KCNN4) conductance, Na-activated K channels (Slo2), voltage-gated (SCN) Na+ and Na+ leak channels, nonselective (NALCN) channels, the Na K-ATPase, and hyperpolarization-activated cation channels. We finish by assessing how three key hormones— oxytocin, estrogen, and progesterone—modulate and integrate excitability throughout gestation. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mitochondrial form, function and signalling in aging

2016 ◽  
Vol 473 (20) ◽  
pp. 3421-3449 ◽  
Author(s):  
Ignacio Amigo ◽  
Fernanda M. da Cunha ◽  
Maria Fernanda Forni ◽  
Wilson Garcia-Neto ◽  
Pâmela A. Kakimoto ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Energy Homeostasis ◽  
Cell Types ◽  
Redox Balance ◽  
Whole Body ◽  
Model Organisms ◽  
Resistance To Stress ◽  
Whole Body Metabolism ◽  
And Function ◽  
Different Characteristics

Aging is often accompanied by a decline in mitochondrial mass and function in different tissues. Additionally, cell resistance to stress is frequently found to be prevented by higher mitochondrial respiratory capacity. These correlations strongly suggest mitochondria are key players in aging and senescence, acting by regulating energy homeostasis, redox balance and signalling pathways central in these processes. However, mitochondria display a wide array of functions and signalling properties, and the roles of these different characteristics are still widely unexplored. Furthermore, differences in mitochondrial properties and responses between tissues and cell types, and how these affect whole body metabolism are also still poorly understood. This review uncovers aspects of mitochondrial biology that have an impact upon aging in model organisms and selected mammalian cells and tissues.

Phospholipid Scrambling by G Protein–Coupled Receptors

2021 ◽  
Vol 51 (1) ◽  
Author(s):  
George Khelashvili ◽  
Anant K. Menon
Keyword(s):  
G Protein ◽  
Conformational Changes ◽  
Credit Card ◽  
Lipid Membrane ◽  
G Protein Coupled Receptors ◽  
Annual Review ◽  
Publication Date ◽  
Flip Flop ◽  
G Protein Coupled

Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein–coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. In liposomes, opsin scrambles lipids at a unitary rate of >100,000 per second. Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions that expose a polar groove between transmembrane helices 6 and 7. This groove enables transbilayer lipid movement, conceptualized as the swiping of a credit card (lipid) through a card reader (GPCR). Conformational changes that facilitate scrambling are distinct from those associated with GPCR signaling. In this review, we discuss the physiological significance of GPCR scramblase activity and the modes of its regulation in cells. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Adipose Tissue Fibrosis in Obesity: Etiology and Challenges

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Geneviève Marcelin ◽  
Emmanuel L. Gautier ◽  
Karine Clément
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Tissue Fibrosis ◽  
Adipose Tissue Remodeling ◽  
Metabolic Dysfunctions ◽  
Body Energy

Obesity is a chronic and progressive process affecting whole-body energy balance and is associated with comorbidities development. In addition to increased fat mass, obesity induces white adipose tissue (WAT) inflammation and fibrosis, leading to local and systemic metabolic dysfunctions, such as insulin resistance (IR). Accordingly, limiting inflammation or fibrosis deposition may improve IR and glucose homeostasis. Although no targeted therapy yet exists to slow or reverse adipose tissue fibrosis, a number of findings have clarified the underlying cellular and molecular mechanisms. In this review, we highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Generating and Using Transcriptomically Based Retinal Cell Atlases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Karthik Shekhar ◽  
Joshua R. Sanes
Keyword(s):  
Expression Patterns ◽  
Retinal Disease ◽  
Cell Types ◽  
Retinal Cell ◽  
Annual Review ◽  
Publication Date ◽  
Vertebrate Species ◽  
Retinal Cells ◽  
Vision Science ◽  
The Brain

It has been known for over a century that the basic organization of the retina is conserved across vertebrates. It has been equally clear that retinal cells can be classified into numerous types, but only recently have methods been devised to explore this diversity in unbiased, scalable, and comprehensive ways. Advances in high-throughput single-cell RNA-sequencing (scRNA-seq) have played a pivotal role in this effort. In this article, we outline the experimental and computational components of scRNA-seq and review studies that have used them to generate retinal atlases of cell types in several vertebrate species. These atlases have enabled studies of retinal development, responses of retinal cells to injury, expression patterns of genes implicated in retinal disease, and the evolution of cell types. Recently, the inquiry has expanded to include the entire eye and visual centers in the brain. These studies have enhanced our understanding of retinal function and dysfunction and provided tools and insights for exploring neural diversity throughout the brain. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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