scholarly journals Irisin a Novel Metabolic Biomarker: Present Knowledge and Future Directions

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ilse Yessabel Martinez Munoz ◽  
Eneida del Socorro Camarillo Romero ◽  
Jose de Jesus Garduno Garcia
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Type I ◽  
Protein Cleavage ◽  
Brown Adipose ◽  
New Findings ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain

The rising prevalence of chronic diseases such as type 2 diabetes and cardiovascular diseases owing to fat mass excess has been described. In recent years, muscle function/dysfunction has become relevant in metabolic homeostasis. Irisin was described as an exercise-induced myokine. It is the product of type I membrane protein cleavage encoded by the fibronectin type III domain containing 5 (FNDC5) gene. The main beneficial function attributable to irisin is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis. Irisin has also been described as a hormone that may have a key role in glucose homeostasis. The way the association of type 2 diabetes with obesity occurs is not fully understood. In recent years, the possible pathways through which irisin could interact with other organs such as the brain or bone have been described. The present paper intends to review the new findings and possible new directions in irisin research.

scholarly journals The Mineralocorticoid Receptor Antagonist Eplerenone Suppress Interstitial Fibrosis in Subcutaneous Adipose Tissue in Type 2 Diabetes Patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Marie Louise Johansen ◽  
Jaime Ibarrola ◽  
Amaya Fernández-Celis ◽  
Morten Schou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Subcutaneous Adipose Tissue ◽  
Mineralocorticoid Receptor ◽  
Prostaglandin D2 ◽  
Type I ◽  
Mineralocorticoid Receptor Antagonist ◽  
Subcutaneous Adipose

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association between the MR, fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present sub-study including 30 participants was prespecified as part of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, randomizing patients to either high dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examinations and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen type I and VI, and the profibrotic factor α-smooth muscle actin, as compared to placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase–associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusions, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

scholarly journals Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs

2019 ◽  
Vol 8 (6) ◽  
pp. 854 ◽  
Author(s):  
Min-Woo Lee ◽  
Mihye Lee ◽  
Kyoung-Jin Oh
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Disturbances ◽  
Endocrine Organ ◽  
Brown Adipose ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site for initiation and aggravation of obesity and T2DM. As a key endocrine organ, the adipose tissue communicates with other organs, such as the brain, liver, muscle, and pancreas, for the maintenance of energy homeostasis. Two different types of adipose tissues—the white adipose tissue (WAT) and brown adipose tissue (BAT)—secrete bioactive peptides and proteins, known as “adipokines” and “batokines,” respectively. Some of them have beneficial anti-inflammatory effects, while others have harmful inflammatory effects. Recently, “exosomal microRNAs (miRNAs)” were identified as novel adipokines, as adipose tissue-derived exosomal miRNAs can affect other organs. In the present review, we discuss the role of adipose-derived secretory factors—adipokines, batokines, and exosomal miRNA—in obesity and T2DM. It will provide new insights into the pathophysiological mechanisms involved in disturbances of adipose-derived factors and will support the development of adipose-derived factors as potential therapeutic targets for obesity and T2DM.

Reduction of Insulin Signaling Upregulates Angiopoietin-like Protein 4 Through Elevated Free Fatty Acids in Diabetic Mice

2011 ◽  
Vol 120 (03) ◽  
pp. 139-144 ◽  
Author(s):  
N. Mizutani ◽  
N. Ozaki ◽  
Y. Seino ◽  
A. Fukami ◽  
E. Sakamoto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Serum Triglyceride ◽  
Diabetic Mice ◽  
Brown Adipose

AbstractAngiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved.Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks.The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells.These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

scholarly journals Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1482
Author(s):  
Ahmad Agil ◽  
Miguel Navarro-Alarcon ◽  
Fatma Abo Zakaib Ali ◽  
Ashraf Albrakati ◽  
Diego Salagre ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Fat ◽  
Superoxide Dismutase Activity ◽  
Atp Production ◽  
Brown Adipose ◽  
Zdf Rats

Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted.

Modulation of energy balance by fibroblast growth factor 21

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Carlos A. Aguilar-Salinas
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Metabolic Syndrome ◽  
Brown Adipose

AbstractFibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through “browning” of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.

Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects

2014 ◽  
Vol 19 (1) ◽  
Author(s):  
Jennifer Honek ◽  
Sharon Lim ◽  
Carina Fischer ◽  
Hideki Iwamoto ◽  
Takahiro Seki ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Causes Of Death ◽  
Brown Adipose ◽  
Common Causes ◽  
Brown Adipose Tissue Thermogenesis ◽  
Thermogenic Capacity

AbstractThe number of obese and overweight individuals is globally rising, and obesity-associated disorders such as type 2 diabetes, cardiovascular disease and certain types of cancer are among the most common causes of death. While white adipose tissue is the key player in the storage of energy, active brown adipose tissue expends energy due to its thermogenic capacity. Expanding and activating brown adipose tissue using pharmacological approaches therefore might offer an attractive possibility for therapeutic intervention to counteract obesity and its consequences for metabolic health.

scholarly journals Brown and Beige Fat: Therapeutic Potential in Obesity

2014 ◽  
Vol 6 (2) ◽  
pp. 65
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Therapeutic Effects ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Adipose Organ

BACKGROUND: The epidemic of obesity and type 2 diabetes presents a serious challenge to scientific and biomedical communities worldwide. There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function.CONTENT: Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible ‘brown-like’ adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.SUMMARY: The complexity of adipose tissue presents numerous challenges but also several opportunities for therapeutic intervention. There is persuasive evidence from animal models that enhancement of the function of brown adipocytes, beige adipocytes or both in humans could be very effective for treating type 2 diabetes and obesity. Moreover, there are now an extensive variety of factors and pathways that could potentially be targeted for therapeutic effects. In particular, the discoveries of circulating factors, such as irisin, fibroblast growth factor (FGF)21 and natriuretic peptides, that enhance brown and beige fat function in mice have garnered tremendous interest. Certainly, the next decade will see massive efforts to use beige and brown fat to ameliorate human metabolic disease.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, adipose organ, thermogenesis, energy expenditure

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