scholarly journals Hypothalamic primary cilium: A hub for metabolic homeostasis

2021 ◽  
Author(s):  
Dong Joo Yang ◽  
Jessica Hong ◽  
Ki Woo Kim
Keyword(s):  
Energy Balance ◽  
Primary Cilium ◽  
Metabolic Disorders ◽  
Primary Cilia ◽  
Metabolic Homeostasis ◽  
Ciliary Function ◽  
Insufficient Physical Activity ◽  
Metabolic Imbalance ◽  
Global Health Problem

AbstractObesity is a global health problem that is associated with adverse consequences such as the development of metabolic disorders, including cardiovascular disease, neurodegenerative disorders, and type 2 diabetes. A major cause of obesity is metabolic imbalance, which results from insufficient physical activity and excess energy intake. Understanding the pathogenesis of obesity, as well as other metabolic disorders, is important in the development of methods for prevention and therapy. The coordination of energy balance takes place in the hypothalamus, a major brain region that maintains body homeostasis. The primary cilium is an organelle that has recently received attention because of its role in controlling energy balance in the hypothalamus. Defects in proteins required for ciliary function and formation, both in humans and in mice, have been shown to cause various metabolic disorders. In this review, we provide an overview of the critical functions of primary cilia, particularly in hypothalamic areas, and briefly summarize the studies on the primary roles of cilia in specific neurons relating to metabolic homeostasis.

scholarly journals The PCP effector Fuzzy controls cilial assembly and signaling by recruiting Rab8 and Dishevelled to the primary cilium

2013 ◽  
Vol 24 (5) ◽  
pp. 555-565 ◽  
Author(s):  
Yulia Zilber ◽  
Sima Babayeva ◽  
Jung Hwa Seo ◽  
Jia Jia Liu ◽  
Steven Mootin ◽  
...  
Keyword(s):  
Basal Body ◽  
Primary Cilium ◽  
Planar Cell Polarity ◽  
Primary Cilia ◽  
Wnt Pathway ◽  
Vertebrate Development ◽  
Cellular Processes ◽  
Ciliary Function ◽  
Pcp Signaling ◽  
Canonical Wnt

The planar cell polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically projecting solitary organelle that is generated via polarized intracellular trafficking. Because it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector Fuzzy affects PCP signaling and formation of primary cilia; however, the mechanisms underlying these processes are largely unknown. Here we report that Fuzzy localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. We propose a mechanism by which Fuzzy participates in ciliogenesis and affects both canonical WNT and PCP signaling.

Role of adenosine monophosphate-activated protein kinase as a regulator of cell energy balance in patients with metabolic disorders

2021 ◽  
Author(s):  
L. V. Zhuravlyova ◽  
Yu. D. Stoianova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Energy Balance ◽  
Human Body ◽  
Diabetes Mellitus Type 2 ◽  
Metabolic Disorders ◽  
Diabetes Mellitus Type ◽  
Metabolic Processes ◽  
Cell Energy

The combination of diabetes mellitus type 2 and gout is common. It has been established that prolonged hyperuricemia leads to insulin resistance and suppresses the effects of insulin, which is why the study of pathogenetic links in the formation of metabolic disorders in synergistic pathologies is relevant. AMPK has been shown to be a regulator of cell energy balance, which plays an important role in preventing the development of insulin resistance. The purpose of this review is to determine the impact of AMPK on carbohydrate, lipid and purine metabolism in patients with diabetes mellitus type 2 and gout. The realization of the effects of AMPK on metabolic processes in the human body occurs in two main ways — inhibition of anabolism and stimulation of catabolism, which will be discussed in the article. It is advisable to consider the mechanisms of action of indirect activators of AMPK as potential components for the comprehensive treatment of patients with metabolic disorders. The mechanisms of activation and inhibition of AMPK are not investigated enough, but it is known that AMPK plays a significant role in the main metabolic processes in the human body. The mechanisms of cell sensitivity to most energy‑containing molecules and substances directly depend on the AMPK activation degree. The presence of these dependencies may be evaluated in the case of metabolic diseases. Thus, further study of the effects of AMPK and its influence on carbohydrate, lipid and purine metabolism is necessary, due to the possibility of predicting the formation of insulin resistance, the severity of diabetes mellitus type 2 in combination with gout, and optimizing treatment in patients with comorbid pathology.

Changes in Energy Balance during Dapagliflozin Therapy in Type 2 Diabetes—The Energize Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1163-P ◽  
Author(s):  
SURYA PANICKER RAJEEV ◽  
CARL A. ROBERTS ◽  
DANIEL J. CUTHBERTSON ◽  
VICTORIA S. SPRUNG ◽  
EMILY BROWN ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Energy Balance

Novel and Practical Approaches to Manage Diet-induced Metabolic Disorders: Part-I

2020 ◽  
Vol 26 (39) ◽  
pp. 4953-4954
Author(s):  
Mallikarjuna Korivi ◽  
Betty Revon Liu
Keyword(s):  
Metabolic Disorders ◽  
Dietary Habits ◽  
Healthy Lifestyle ◽  
Modern World ◽  
Successful Management ◽  
Exercise Interventions ◽  
Beneficial Effects ◽  
Effective Strategies ◽  
Dietary Strategies ◽  
Global Health Problem

Metabolic syndrome (MetS) which is caused by poor dietary habits and sedentary behavior is a serious global health problem. MetS is a cluster of risk factors, represented by central obesity, hyperglycemia, dyslipidemia, and hypertension. In the 21st century, MetS and associated comorbidities, including obesity, diabetes and cardiovascular diseases, are the major threats to human health. Practical dietary strategies, nutritional bioactive compounds and a healthy lifestyle are claimed to be efficient in the management of one or more components of MetS. Nevertheless successful management of MetS and commodities is still a major concern. Since hyperglycemia, inflammation and redox imbalance are intrinsically involved in the progression of MetS comorbidities, finding effective strategies that precisely target these systems is highly warranted. In this scenario, pharmacological and non-pharmacological approaches with or without dietary patterns, phytochemicals or exercise interventions are the practical strategies to combat MetS and associated diseases. However, designing and prescribing of optimal nutritional patterns and exercise regimens remains a big challenge to achieve the maximum beneficial effects. This thematic issue addressed the concerns and provided practical strategies to overcome the malady of MetS in the modern world.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

scholarly journals Magnesium, Little Known But Possibly Relevant: A Link between NASH and Related Comorbidities

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 125
Author(s):  
Jorge Simón ◽  
Teresa Cardoso Delgado ◽  
Luis Alfonso Martinez-Cruz ◽  
Maria Luz Martínez-Chantar
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Inflammatory Process ◽  
Fibrotic Response ◽  
Hepatic Lipid Accumulation ◽  
Root Cause ◽  
Worldwide Population ◽  
Global Health Problem

Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a quarter of the worldwide population. Nevertheless, the development of NASH is often surrounded by a pathological context with other comorbidities, such as cardiovascular diseases, obesity, insulin resistance or type 2 diabetes mellitus. Dietary imbalances are increasingly recognized as the root cause of these NASH-related comorbidities. In this context, a growing concern exists about whether magnesium consumption in the general population is sufficient. Hypomagnesemia is a hallmark of the aforementioned NASH comorbidities, and deficiencies in magnesium are also widely related to the triggering of complications that aggravate NASH or derived pathologies. Moreover, the supplementation of this cation has proved to reduce mortality from hepatic complications. In the present review, the role of magnesium in NASH and related comorbidities has been characterized, unraveling the relevance of maintaining the homeostasis of this cation for the correct functioning of the organism.

scholarly journals Advances in high-density lipoprotein physiology: surprises, overturns, and promises

2016 ◽  
Vol 310 (1) ◽  
pp. E1-E14 ◽  
Author(s):  
Caterina Constantinou ◽  
Eleni A. Karavia ◽  
Eva Xepapadaki ◽  
Peristera-Ioanna Petropoulou ◽  
Eugenia Papakosta ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Density Lipoprotein ◽  
Pulmonary Diseases ◽  
Brain Disorders ◽  
Nonalcoholic Fatty Liver ◽  
Disease States ◽  
And Function

Emerging evidence strongly supports that changes in the HDL metabolic pathway, which result in changes in HDL proteome and function, appear to have a causative impact on a number of metabolic disorders. Here, we provide a critical review of the most recent and novel findings correlating HDL properties and functionality with various pathophysiological processes and disease states, such as obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, inflammation and sepsis, bone and obstructive pulmonary diseases, and brain disorders.

scholarly journals Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1947
Author(s):  
Alice-Anaïs Varlet ◽  
Emmanuèle Helfer ◽  
Catherine Badens
Keyword(s):  
Mechanical Properties ◽  
Signaling Pathways ◽  
Metabolic Disorders ◽  
Lamin A ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Almost All ◽  
Type V

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis.

Sign in / Sign up

Export Citation Format

Share Document