scholarly journals Control of Adipose Cell Browning and Its Therapeutic Potential

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 471
Author(s):  
Fernando Lizcano ◽  
Felipe Arroyave
Keyword(s):  
Metabolic Diseases ◽  
Environmental Changes ◽  
Therapeutic Potential ◽  
The Body ◽  
Fat Cells ◽  
Lipid Inclusion ◽  
Nutritional Conditions ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Embryonic Origin

Adipose tissue is the largest endocrine organ in humans and has an important influence on many physiological processes throughout life. An increasing number of studies have described the different phenotypic characteristics of fat cells in adults. Perhaps one of the most important properties of fat cells is their ability to adapt to different environmental and nutritional conditions. Hypothalamic neural circuits receive peripheral signals from temperature, physical activity or nutrients and stimulate the metabolism of white fat cells. During this process, changes in lipid inclusion occur, and the number of mitochondria increases, giving these cells functional properties similar to those of brown fat cells. Recently, beige fat cells have been studied for their potential role in the regulation of obesity and insulin resistance. In this context, it is important to understand the embryonic origin of beige adipocytes, the response of adipocyte to environmental changes or modifications within the body and their ability to transdifferentiate to elucidate the roles of these cells for their potential use in therapeutic strategies for obesity and metabolic diseases. In this review, we discuss the origins of the different fat cells and the possible therapeutic properties of beige fat cells.

scholarly journals Comparative Transcriptome Profiling of Cold Exposure and β3-AR Agonist CL316,243-Induced Browning of White Fat

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Li ◽  
Xiaodan Ping ◽  
Yankang Zhang ◽  
Guoqiang Li ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Adrenergic Receptor ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Transcriptome Profiling ◽  
Sequencing Analysis ◽  
Qpcr Analysis ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
White Fat

Beige adipocytes are newly identified thermogenic-poised adipocytes that could be activated by cold or β3-adrenergic receptor (β3-AR) signaling and offer therapeutic potential for treating obesity and metabolic diseases. Here we applied RNA-sequencing analysis in the beige fat of mice under cold exposure or β3-AR agonist CL316,243 (CL) treatment to provide a comparative and comprehensive analysis for the similarity and heterogeneity of these two stimulants. Importantly, via KEGG analysis, we found that cold and CL commonly induced oxidative phosphorylation. Meanwhile, cold increased glycerolipid and amino acids metabolism while CL treatment triggered a broader spectrum of metabolic responses including carbohydrate metabolism. Besides, cold or CL treatment featured greater heterogeneity in downregulated gene programs. Of note, the top changed genes in each category were confirmed by qPCR analysis. Overall, our analysis provided a better understanding of the heterogeneity of differential models for beige adipocytes activation and a possible clue for optimizing β3-AR agonists in the future.

scholarly journals Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

2021 ◽  
Vol 22 (11) ◽  
pp. 5906
Author(s):  
Bruna B. Brandão ◽  
Ankita Poojari ◽  
Atefeh Rabiee
Keyword(s):  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Comprehensive Overview ◽  
Glucose Levels ◽  
Increase Energy Expenditure ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Thermogenic Adipocytes

The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

scholarly journals NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Na Xie ◽  
Lu Zhang ◽  
Wei Gao ◽  
Canhua Huang ◽  
Peter Ernst Huber ◽  
...  
Keyword(s):  
Communication Networks ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Environmental Changes ◽  
Therapeutic Potential ◽  
Nad Metabolism ◽  
Oxidation Reduction ◽  
Enzyme Cofactors ◽  
Genotoxic Factors ◽  
Post Synthesis

Abstract Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

scholarly journals Regulatory networks of non-coding RNAs in brown/beige adipogenesis

2015 ◽  
Vol 35 (5) ◽  
Author(s):  
Shaohai Xu ◽  
Peng Chen ◽  
Lei Sun
Keyword(s):  
Regulatory Networks ◽  
The Body ◽  
Bat Activity ◽  
Non Coding Rna ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
And Function ◽  
Long Non Coding Rna

BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences.

scholarly journals Breaking BAT: can browning create a better white?

2015 ◽  
Vol 228 (1) ◽  
pp. R19-R29 ◽  
Author(s):  
Amy Warner ◽  
Jens Mittag
Keyword(s):  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Direct Stimulation ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Underlying Mechanisms ◽  
Body Energy

Obesity and its comorbidities are a growing problem worldwide. In consequence, several new strategies have been proposed to promote weight loss and improve insulin sensitivity. Recently, it has been demonstrated that certain populations of white adipocytes can be ‘browned’, i.e., recruited to a more brown-like adipocyte, capable of thermogenesis through increased expression of uncoupling protein 1. The list of browning agents that induce these so-called beige adipocytes is growing constantly. However, the underlying mechanisms are often poorly understood, with the possibility that some of these agents cause browning as a secondary effect. Moreover, it remains unclear whether beige adipocytes can contribute sufficiently to affect whole-body energy expenditure in a functionally significant manner. This review presents an overview of the different molecular pathways leading to the induction of beige fat, including direct stimulation and indirect actions on the CNS or the immune system. We discuss the available evidence on the capacity of beige adipocytes to influence whole-body energy expenditure in rodents, and lastly outline the potential problems of translating browning capacity into the potential treatment of human metabolic diseases.

scholarly journals Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kun-Ping Li ◽  
Yang Yu ◽  
Min Yuan ◽  
Chu-Mei Zhang ◽  
Xiang-Lu Rong ◽  
...  
Keyword(s):  
Western Blotting ◽  
Glucose Intolerance ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Resistance Index ◽  
The Body ◽  
Molecular Networks ◽  
Hepatic Tissue ◽  
Oral Glucose

The progressive increase of metabolic diseases underscores the necessity for developing effective therapies. Although we found Tian-Huang formula (THF) could alleviate metabolic disorders, the underlying mechanism remains to be fully understood. In the present study, firstly, male Sprague-Dawley rats were fed with high-fat diet plus high-fructose drink (HFF, the diet is about 60% of calories from fat and the drink is 12.5% fructose solution) for 14 weeks to induce hepatosteatosis and glucose intolerance and then treated with THF (200 mg/kg) for 4 weeks. Then, metabolomics analysis was performed with rat liver samples and following the clues illustrated by Ingenuity Pathway Analysis (IPA) with the metabolomics discoveries, RT-qPCR and Western blotting were carried out to validate the putative pathways. Our results showed that THF treatment reduced the body weight from 735.1 ± 81.29 to 616.3 ± 52.81 g and plasma triglyceride from 1.5 ± 0.42 to 0.88 ± 0.33 mmol/L; meanwhile, histological examinations of hepatic tissue and epididymis adipose tissue showed obvious alleviation. Compared with the HFF group, the fasting serum insulin and blood glucose level of the THF group were improved from 20.77 ± 6.58 to 9.65 ± 5.48 mIU/L and from 8.96 ± 0.56 to 7.66 ± 1.25 mmol/L, respectively, so did the serum aspartate aminotransferase, insulin resistance index, and oral glucose tolerance ( p  = 0.0019, 0.0053, and 0.0066, respectively). Furthermore, based on a list of 32 key differential endogenous metabolites, the molecular networks generated by IPA suggested that THF alleviated glucose intolerance and hepatosteatosis by activating phosphatidylinositol-3 kinase (PI3K) and low-density lipoprotein receptor (LDL-R) involved pathways. RT-qPCR and Western blotting results confirmed that THF alleviated hepatic steatosis and glucose intolerance partly through protein kinase B- (AKT-) sterol regulatory element-binding protein (SREBP) nexus. Our findings shed light on molecular mechanisms of THF on alleviating metabolic diseases and provided further evidence for developing its therapeutic potential.

Integrating Focusing and Differentiation: A Therapeutic Path for Couples in Intimate Relationships

2018 ◽  
Vol 3 ◽  
Author(s):  
Evi Zohar
Keyword(s):  
Couples Therapy ◽  
Therapeutic Potential ◽  
Well Being ◽  
Point Of View ◽  
The Body ◽  
Self Awareness ◽  
Emotional Healing ◽  
Felt Sense ◽  
Inner World

Continuing the workshop I've given in the WPC Paris (2017), this article elaborates my discussion of the way I interlace Focusing with Differentiation Based Couples Therapy (Megged, 2017) under the systemic view, in order to facilitate processes of change and healing in working with intimate couples. This article presents the theory and rationale of integrating Differentiation (Bowen, 1978; Schnarch, 2009; Megged, 2017) and Focusing (Gendlin, 1981) approaches, and its therapeutic potential in couple's therapy. It is written from the point of view of a practicing professional in order to illustrate the experiential nature and dynamics of the suggested therapeutic path. Differentiation is a key to mutuality. It offers a solution to the central struggle of any long term intimate relationship: balancing two basic life forces - the drive for individuality and the drive for togetherness (Schnarch, 2009). Focusing is a body-oriented process of self-awareness and emotional healing, in which one learns to pay attention to the body and the ‘Felt Sense’, in order to unfold the implicit, keep it in motion at the precise pace it needs for carrying the next step forward (Gendlin, 1996). Combining Focusing and Differentiation perspectives can cultivate the kind of relationship where a conflict can be constructively and successfully held in the inner world of each partner, while taking into consideration the others' well-being. This creates the possibility for two people to build a mutual emotional field, open to changes, permeable and resilient.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

Roux-en-Y Gastrointestinal Bypass Promotes Activation of TGR5 and Peptide YY

2020 ◽  
Vol 20 (8) ◽  
pp. 1262-1267
Author(s):  
Haojun Yang ◽  
Hanyang Liu ◽  
YuWen Jiao ◽  
Jun Qian
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
The Body ◽  
Wild Type ◽  
L Cells ◽  
Body Weights ◽  
Gastrointestinal Bypass ◽  
G Protein Coupled

Background: G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). Methods: Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. Results: The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). Conclusion: Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.

scholarly journals Wearable Vibration Sensor for Measuring the Wing Flapping of Insects

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 593
Author(s):  
Ryota Yanagisawa ◽  
Shunsuke Shigaki ◽  
Kotaro Yasui ◽  
Dai Owaki ◽  
Yasuhiro Sugimoto ◽  
...  
Keyword(s):  
High Speed ◽  
Environmental Changes ◽  
Underlying Mechanism ◽  
Indirect Measurement ◽  
Feedback Mechanism ◽  
The Body ◽  
Vibration Sensor ◽  
Wingbeat Frequency ◽  
Film Sensor ◽  
Insect Wing

In this study, we fabricated a novel wearable vibration sensor for insects and measured their wing flapping. An analysis of insect wing deformation in relation to changes in the environment plays an important role in understanding the underlying mechanism enabling insects to dynamically interact with their surrounding environment. It is common to use a high-speed camera to measure the wing flapping; however, it is difficult to analyze the feedback mechanism caused by the environmental changes caused by the flapping because this method applies an indirect measurement. Therefore, we propose the fabrication of a novel film sensor that is capable of measuring the changes in the wingbeat frequency of an insect. This novel sensor is composed of flat silver particles admixed with a silicone polymer, which changes the value of the resistor when a bending deformation occurs. As a result of attaching this sensor to the wings of a moth and a dragonfly and measuring the flapping of the wings, we were able to measure the frequency of the flapping with high accuracy. In addition, as a result of simultaneously measuring the relationship between the behavior of a moth during its search for an odor source and its wing flapping, it became clear that the frequency of the flapping changed depending on the frequency of the odor reception. From this result, a wearable film sensor for an insect that can measure the displacement of the body during a particular behavior was fabricated.

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