Circulating and adipose tissue matrix metalloproteinases in cardiometabolic risk environments: pathophysiological aspects

2014 ◽  
Vol 17 (2) ◽  
Author(s):  
Gabriela Berg ◽  
Laura Schreier ◽  
Veronica Miksztowicz
Keyword(s):  
Adipose Tissue ◽  
Matrix Metalloproteinases ◽  
Plaque Rupture ◽  
Hormone Replacement ◽  
Protective Role ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Fat Tissue ◽  
Risk Environments ◽  
Tissue Matrix ◽  
Circulating Levels

AbstractMatrix metalloproteinases (MMPs) play an important role during physiological tissue remodeling in embryonic development and angiogenesis, as well as in pathophysiological conditions such as obesity and development and vulnerability of atherosclerotic plaque. Moreover, MMP circulating levels have emerged as potential biomarkers of cardiovascular disease. MMP expression and activity are regulated by different factors such as insulin resistance and obesity. Expanded fat tissue has been demonstrated to be an active organ, where MMPs also exert a role in adipogenesis, angiogenesis, and proliferation of extracellular matrix (ECM). However, the lack of association between adipose tissue and plasma levels of some MMPs, specifically MMP-2 and MMP-9, suggests that this tissue is not a major contributor to circulating gelatinases. MMPs are also co-expressed or co-repressed in response to inflammatory adipocytokines, like adiponectin and leptin. Adiponectin may also play a protective role in plaque rupture through selectively increasing the tissue inhibitor of metalloproteinase (TIMP) expression. Leptin induces the expression of MMP-2 activators as well as the expression of MMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore, sex hormones also participate in MMP regulation. In postmenopausal women, hormone replacement therapy produces an increase in MMP activity, leading to a breakdown in ECM homeostasis and accelerated progression of vascular pathologies. Besides, in men, an inverse relationship between testosterone levels and MMP-2 activity has been described. It is still necessary to go forward in the study of MMPs in different metabolic situations to corroborate their role as vulnerable plaque biomarkers.

scholarly journals Hyperphagia and Obesity in Female Mice Lacking Tissue Inhibitor of Metalloproteinase-1

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1697-1704 ◽  
Author(s):  
Isabelle Gerin ◽  
Gwendolyn W. Louis ◽  
Xuan Zhang ◽  
Tyler C. Prestwich ◽  
T. Rajendra Kumar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Signal Transducer ◽  
Altered Expression ◽  
Total Body ◽  
Transcription 3

Certain matrix metalloproteinases and their regulators, the tissue inhibitors of metalloproteinases (TIMPs), are involved in development and remodeling of adipose tissue. In studying Timp1<tm1Pds> mice, which have a null mutation in Timp1 (Timp1−/−), we observed that females exhibit increased body weight by 3 months of age due to increased total body lipid and adipose tissue. Whereas Timp1−/− mice have increased size and number of adipocytes, they also display increased food intake despite hyperleptinemia, suggesting that alterations in hypothalamic leptin action or responsiveness may underlie their weight gain. Indeed, leptin promotes the expression of Timp1 mRNA in the hypothalamus, and leptin signaling via signal transducer and activator of transcription-3 mediates the expression of hypothalamic Timp1. Furthermore, Timp1−/− mice demonstrate increased food intake and altered expression of certain hypothalamic neuropeptide genes prior to elevated weight gain. Thus, whereas previous data suggested roles for matrix metalloproteinases and TIMPs in the regulation of adipose tissue, these data reveal that Timp1 mRNA is induced by leptin in the hypothalamus and that expression and action of Timp1 contributes to the regulation of feeding and energy balance.

scholarly journals The Expression of Adipose Tissue-Derived Cardiotrophin-1 in Humans with Obesity

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 24
Author(s):  
Jacqueline Stephens ◽  
Eric Ravussin ◽  
Ursula White
Keyword(s):  
Heart Failure ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Protective Role ◽  
Obese Women ◽  
Potential Therapeutic Target ◽  
Endocrine Organ ◽  
New Knowledge ◽  
Intrahepatic Lipid ◽  
Circulating Levels

Cardiotrophin-1 (CT-1) is a gp130 cytokine that was previously characterized for its effects on cardiomyocytes and identified as a marker of heart failure. More recent studies reported elevated circulating levels of CT-1 in humans with obesity and metabolic syndrome (MetS). However, a subsequent rodent study implicated CT-1 as a potential therapeutic target for obesity and MetS. Adipose tissue (AT) is broadly acknowledged as an endocrine organ and is a substantial source of CT-1. However, no study has examined the expression of adipose-derived CT-1 in humans. We present the first analysis of CT-1 mRNA expression in subcutaneous AT and its association with clinical variables in 22 women with obesity and 15 men who were 40% overfed for 8-weeks. We observed that CT-1 expression was higher in the subcutaneous abdominal (scABD) than the femoral (scFEM) depot. Importantly, we reveal that scFEM but not scABD, CT-1 expression was negatively associated with visceral adiposity and intrahepatic lipid, while positively correlated with insulin sensitivity in obese women. Also, men with higher CT-1 levels at baseline had less of a decline in insulin sensitivity in response to overfeeding. Our data provide new knowledge on the regulation of adipose-derived CT-1 in obesity and during weight gain in response to overfeeding in humans and suggest that CT-1 may play a protective role in obesity and related disorders.

The Important Roles of Matrix Metalloproteinases in the Pathophysiology of Obesity

2017 ◽  
Vol 68 (7) ◽  
pp. 1481-1484 ◽  
Author(s):  
Radu Mihail Mirica ◽  
Mihai Ionescu ◽  
Alexandra Mirica ◽  
Octav Ginghina ◽  
Razvan Iosifescu ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Matrix Metalloproteinases ◽  
English Language ◽  
Critical Role ◽  
Animal Experiments ◽  
Hdl Cholesterol ◽  
Tissue Growth ◽  
Basement Membranes ◽  
Body Weight Reduction

Obesity involves the growth of adipose tissue cells (adipocytes and preadipocytes), as well as microvascular endothelial cells. Matrix metalloproteinases (MMPs) are relevant ezymes for the modulation of extracellular matrix (ECM) and adipocyte and preadipocytes differentiation. They are elevated in obese patients, generating abnormal ECM metabolism.[1]. This article proposes a thorough study of literature with focus on the important roles of matrix metalloproteinases in the pathophysiology of obesity. The article represents a narrative review based on an English-language PubMed research of the medical literature regardind important aspects of the proposed aim. MMP-2 activity was signi�cantly higher than MMP-9, both activities were detectable. MMP-9 was strongly correlated with body weight parameters before surgery, as well as after significant body weight reduction as a result of bariatric surgery. Concerning MMP-2 and MMP-9 they are also involved in the turnover of basement membranes both those of adipose tissue and endothelial. MMP-9 levels were moderately correlated with HDL cholesterol levels. Taken together, the present data suggest that changes in ECM through MMP-mediated degradation might play a critical role in the adipocyte differentiation process. These findings are detected both in clinical trials and in laboratory animal experiments. It is then tempting to speculate that the adipocyte-derived MMPs might represent a new pharmacological target for the inhibition of adipose tissue growth by inhibiting adipose differentiation as well as angiogenic process.

scholarly journals An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

2021 ◽  
Vol 22 (15) ◽  
pp. 7975
Author(s):  
Saioa Gómez-Zorita ◽  
Iñaki Milton-Laskibar ◽  
Laura García-Arellano ◽  
Marcela González ◽  
María P. Portillo
Keyword(s):  
Adipose Tissue ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Current Evidence ◽  
Disease Outcomes ◽  
Lower Activation ◽  
Two Factors ◽  
Obese Subjects ◽  
Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

scholarly journals Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dependent Manner ◽  
Metabolic Dysfunction ◽  
Functional Interaction ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Adhesion Gpcr ◽  
Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

scholarly journals Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1435
Author(s):  
Aimilia Papathanasiou ◽  
Fotios Spyropoulos ◽  
Zoe Michael ◽  
Kyoung Joung ◽  
Despina Briana ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Tricarboxylic Acid Cycle ◽  
Fibroblast Growth Factor 21 ◽  
Mrna Levels ◽  
Rodent Models ◽  
Fatty Acid Binding ◽  
Metabolic Regulators ◽  
Circulating Levels

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

scholarly journals Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Tumor Development ◽  
Cell Types ◽  
Protective Role ◽  
Bioactive Molecules ◽  
Brown Adipose ◽  
Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

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