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 Effects of a 3-Week In-Hospital Body Weight Reduction Program on Cardiovascular Risk Factors, Muscle Performance, and Fatigue: A Retrospective Study in a Population of Obese Adults with or without Metabolic Syndrome

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1495 ◽  
Author(s):  
Antonello E. Rigamonti ◽  
Sabrina Cicolini ◽  
Diana Caroli ◽  
Alessandra De Col ◽  
Massimo Scacchi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Body Weight ◽  
Weight Reduction ◽  
Hdl Cholesterol ◽  
Muscle Performance ◽  
Weight Reduction Program ◽  
Body Weight Reduction ◽  
Reduction Program ◽  
Obese Subjects

Background. In clinical practice, there is the diffuse conviction that obese subjects with metabolic syndrome may be more difficult to treat. Objectives and Methods. The aim of the present study was that to investigate the effectiveness of a 3-week in-hospital body weight reduction program (BWRP) in a large population of obese subjects with and without metabolic syndrome (n = 1922; 222 men and 1700 women, age range 18–83 yr). Outcomes such as body mass index (BMI), total (TOT) and HDL cholesterol, systolic and diastolic blood pressures (SBP and DBP, respectively), coronary heart disease (CHD) score, fatigue severity score (FSS), and stair climbing test (SCT) time were evaluated before and after the intervention (Δ). A sex-, BMI-, and age-related stratification of the obese population with or without metabolic syndrome was applied. Results. When compared to obese subjects without metabolic syndrome, at the basal conditions, obese subjects had a poorer cardiometabolic profile, as demonstrated by higher triglycerides, TOT-cholesterol, DBP, SBP, and CHD score, and a more compromised muscle performance (evaluated by SCT), associated with more perception of fatigue (measured by FSS). Nevertheless, obese subjects with metabolic syndrome obtained more benefits from BWRP than those without metabolic syndrome for some outcomes (i.e., ΔTOT-cholesterol, ΔSBP, and ΔCHD score). Despite these differences, the BWRP-induced weight loss was similar between the two groups (i.e., ΔBMI) as well as the gain of muscle performance (i.e., ΔSCT) and the reduction of fatigue (i.e., ΔFSS). Interestingly, the potentially deleterious fall in HDL-cholesterol levels after BWRP was less evident in obese subjects with metabolic syndrome than those without metabolic syndrome. When pooling all data, the ΔCHD score was associated with age, sex, and metabolic syndrome. The remaining outcomes, such as ΔBMI, ΔFSS, and ΔSCT time, were associated with sex and age but not with metabolic syndrome. Finally, ΔBMI was positively correlated with ΔCHD score, ΔFSS, and ΔSCT time in both obese subjects without metabolic syndrome and obese subjects with metabolic syndrome. Conclusions. When comparing obese subjects undergoing a BWRP, metabolic syndrome is not a negative predictive factor affecting the effectiveness of this intervention in terms of weight loss, muscle performance, and psychological well-being.

Relationship of brown adipose tissue with growth and obesity differences in genetically selected mouse lines

1984 ◽  
Vol 26 (3) ◽  
pp. 339-347 ◽  
Author(s):  
A. M. Saxton ◽  
E. J. Eisen ◽  
J. M. Leatherwood
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Single Gene ◽  
Tissue Growth ◽  
Growth Patterns ◽  
High Fat ◽  
Polygenic Control ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

A recent hypothesis considers brown adipose tissue (BAT) to be an important source of diet-induced thermogenesis (DIT). In turn, DIT and thermogenesis in general are believed to be key factors in the control of obesity of laboratory rodents. This hypothesis was developed from the study of single gene mutant obese rodents. The present research tested this hypothesis in mice with polygenic control of growth and obesity, which is more characteristic of the type of genetic variation expected in human and other mammalian populations. Control and high fat diets were used to test responses of five genetically selected lines of mice showing different patterns of growth and obesity. All lines deposited more fat on the high fat diet, but the most obese line showed the largest increase in BAT and the lipid-free dry (LFD) component of BAT. Use of LFD per unit body weight gave results which supported the hypothesis being tested, but it was argued that this measure is misleading. When brown and white adipose tissue growth relative to body weight were examined, 2 of the 10 line – diet groups showed alterations in BAT growth patterns. However, it was concluded that BAT, if involved at all, was not a major factor in growth and obesity differences.Key words: obesity, polygenes, adipose tissue, quantitative inheritance, mouse.

scholarly journals Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

2015 ◽  
Vol 35 (4) ◽  
pp. 1482-1498 ◽  
Author(s):  
Sang Woo Kim ◽  
Tae-Jun Park ◽  
Jae Heon Choi ◽  
Kanikkai Raja Aseer ◽  
Ji-Young Choi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Proteomic Analysis ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Herbal Medicines ◽  
High Fat ◽  
Body Weight Reduction ◽  
Peptide Mass

Background: One of the most interesting issues in obesity research is why certain humans are obesity-prone (OP) while others are obesity-resistant (OR) upon exposure to a high-calorie diet. However, the pathways responsible for these phenotypic differences are still largely unknown. Methods: In order to discover marker molecules determining susceptibility and/or resistance to obesity in response to high fat diet (HFD) or anti-obesity herbal medicine (TH), we conducted comparative proteomic analysis of white adipose tissue (WAT) from OP, OR, as well as TH-treated mice. Results: OP mice fed HFD gained approximately 33% more body weight than OR mice, and TH significantly reduced body weight gain in HFD-fed mice by 30%. These mice were further subjected to proteomic analysis using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Proteomic data revealed 59 spots that were differentially regulated from a total of 1,045 matched spots, and 57 spots of these were identified as altered WAT proteins between OP and OR mice by peptide mass finger printing. Interestingly, 45 proteins were similarly regulated in OR mice in response to TH treatment. Of these, 10 proteins have already been recognized in the context of obesity; however, other proteins involved in obesity susceptibility or resistance were identified for the first time in the present study. Conclusion: Our results suggest that TH actively contributed to body weight reduction in HFD-fed obese mice by altering protein regulation in WAT, and it was also found that TH-responsive proteins can be used as potent molecules for obesity treatment.

scholarly journals Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan

2019 ◽  
Author(s):  
Camille de Lombares ◽  
Eglantine Heude ◽  
Gladys Alfama ◽  
Anastasia Fontaine ◽  
Rim Hassouna ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Healthy Aging ◽  
Gabaergic Neurons ◽  
Biological Aging ◽  
Gabaergic Interneurons ◽  
Obsessive Compulsive ◽  
Body Weight Reduction ◽  
Brown Adipose ◽  
The Brain

ABSTRACTDlx5 and Dlx6 encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During development Dlx5/6 are important for the differentiation of Parvalbumin (Pvalb)-expressing neurons. Perinatal lethality of homozygous mice in which Dlx5/6 have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show that Dlx5 and Dlx6 are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyse VgatΔDlx5-6 mice in which Dlx5 and Dlx6 are simultaneously inactivated in all GABAergic interneurons. VgatΔDlx5-6 mice present a behavioral pattern suggesting reduction of anxiety and obsessive-compulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-old VgatΔDlx5-6 animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, both VgatΔDlx5-6/+ and VgatΔDlx5-6 mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan through Dlx5/6-dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging.SIGNIFICANCE STATEMENTDlx5 and Dlx6 are transcription factors controlling several developmental processes, including GABAergic neuronal migration and differentiation. To study their function in adult brain, we selectively inactivated both genes in GABAergic interneurons (VgatΔDlx5-6 mice). Mutant mice have reduced anxiety-like and obsessive-compulsive behaviors. Interestingly, VgatΔDlx5-6 mice have a 25% body weight reduction and about 70% less white and brown adipose tissue; their general health status is excellent. VgatΔDlx5-6 mice have a median survival about 33% longer than their control littermates and hallmarks of biological aging are improved. Dlx5/6-dependent regulations in GABAergic neurons could be an entry point to understand how the brain determines the psychophysiological status of the body and, ultimately, longevity and healthy aging.

scholarly journals Adipose Tissue is a Critical Regulator of Osteoarthritis

2020 ◽  
Author(s):  
Kelsey H. Collins ◽  
Kristin L. Lenz ◽  
Eleanor N. Pollitt ◽  
Daniel Ferguson ◽  
Irina Hutson ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Critical Role ◽  
Knee Joints ◽  
Inflammatory Factors ◽  
Paracrine Signaling ◽  
Complex Interactions ◽  
Post Traumatic ◽  
Similar Body ◽  
Cause Of Pain

AbstractOsteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects obese individuals. The mechanisms by which adipose tissue leads to the onset and progression of OA are unclear due to the complex interactions between the metabolic, biomechanical, and inflammatory factors that accompany obesity. We used a murine model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or post-traumatic OA, on either a chow and high fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to post-traumatic OA was reintroduced into LD mice using implantation of adipose tissue derived from wildtype animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a critical mediator of joint degeneration.

Abstract 605: Bone Morphogenetic Protein Inhibitors Play Important Roles in Brown and White Adipogenesis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ana M Blazquez-Medela ◽  
Medet Jumabay ◽  
Kristina I Bostrom
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Body Fat ◽  
Lipid Accumulation ◽  
Adipogenic Differentiation ◽  
Critical Role ◽  
Matrix Gla Protein ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Time Point

Adipose tissue is intimately connected to the development of metabolic syndrome, type 2 diabetes and cardiovascular disease. The near pandemic increase in incidence and prevalence of obesity makes it necessary to understand adipose regulation in order to develop strategies against obesity and its comorbidities. Adipose tissue performs a variety of functions. White adipose tissue (WAT) is responsible for energy storage, hormone production and organ protection, whereas brown adipose tissue (BAT) has a key role in thermogenesis. Previous studies have shown the importance of Bone Morphogenetic Proteins (BMPs) in the differentiation of brown and white adipocytes. BMP4 has been linked to both brown and white adipogenesis and BMP7 is essential for brown adipogenesis. Nevertheless, the role of the BMP inhibitors, which modulate the actions of BMPs, has not yet been elucidated. Our hypothesis is that the BMP inhibitors play important roles in the adipogenic process. Using two different mice models -Matrix Gla Protein (Mgp) KO and Noggin fat-specific KO- we found that the absence of Mgp resulted in dramatic adipose changes, suggesting a critical role in the separation of white and brown adipocytes. Adipocyte-specific deletion of Noggin, however, suggested a role in modulating the size and lipid accumulation in fully differentiated adipocytes. The absence of Mgp led to a reduction in body fat and body weight (3-12 animals per group and time point) whereas the absence of Noggin caused an increase in body fat and body weight (4-18 animals per time point and body weight). Tissue culture experiments using white and brown adipocyte progenitor cells showed specific temporal patterns of the BMPs and BMP-inhibitors that were consistent with the mouse findings. In conclusion, BMP inhibitors are essential in distinguishing brown and white adipogenic differentiation. We hypothesize that MGP is critical in the initial separation, whereas Noggin regulates cell size and lipid accumulation.

Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum

1998 ◽  
Vol 274 (5) ◽  
pp. R1460-R1467 ◽  
Author(s):  
M. DiGirolamo ◽  
J. B. Fine ◽  
K. Tagra ◽  
R. Rossmanith
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Regional Differences ◽  
Wistar Rats ◽  
Cell Number ◽  
Tissue Growth ◽  
Fat Cell ◽  
Fat Depots ◽  
Male Wistar Rats ◽  
Ad Libitum

Adipose tissue grows primarily by a combination of increases in fat cell volume (hypertrophy) and in fat cell number (hyperplasia), but the regional growth pattern of white adipose tissue depots in animal species and in the human is still unclear. In this study we characterized fully the age-related changes in adipose tissue growth, composition, and cellularity of four fat depots of male Wistar rats that varied in age from 7 wk to 15 mo and in body weight from 178 to 808 g. Body weight and the weight of each of the four adipose depots studied (epididymal, mesenteric, subcutaneous inguinal, and retroperitoneal) increased progressively with age and ad libitum feeding. Comparison of the cellularity of the four adipose depots, however, showed remarkable and significant differences in the pattern of growth within the same animals. The cumulative growth of the two intra-abdominal fat depots (mesenteric and epididymal) was due mostly to hypertrophy (increases in cell volume of 83 and 64%, respectively), whereas the growth of the other two depots (retroperitoneal and inguinal) was due predominantly to hyperplasia (increases in cell number of 58 and 65%, respectively). These findings uncover major and unexpected regional differences in the modulation of adipose tissue growth within aging animals fed ad libitum and suggest local, region-specific regulatory controls of this growth.

Understanding Adipocyte Differentiation

1998 ◽  
Vol 78 (3) ◽  
pp. 783-809 ◽  
Author(s):  
FRANCINE M. GREGOIRE ◽  
CYNTHIA M. SMAS ◽  
HEI SOOK SUL
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Critical Role ◽  
Tissue Growth ◽  
Fatty Acid Binding ◽  
Ppar Γ

Gregoire, Francine M., Cynthia M. Smas, and Hei Sook Sul. Understanding Adipocyte Differentiation. Physiol. Rev. 78: 783–809, 1998. — The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation. Growth and differentiation of preadipocytes is controlled by communication between individual cells or between cells and the extracellular environment. Various hormones and growth factors that affect adipocyte differentiation in a positive or negative manner have been identified. In addition, components involved in cell-cell or cell-matrix interactions such as preadipocyte factor-1 and extracellular matrix proteins are also pivotal in regulating the differentiation process. Identification of these molecules has yielded clues to the biochemical pathways that ultimately result in transcriptional activation via PPAR-γ and C/EBP. Studies on the regulation of the these transcription factors and the mode of action of various agents that influence adipocyte differentiation will reveal the physiological and pathophysiological mechanisms underlying adipose tissue development.

scholarly journals Activin A Plays a Critical Role in Adipose Tissue Wasting in the Progression of Cancer Cachexia

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A40-A40
Author(s):  
Yi Luan ◽  
Mikyoung You ◽  
Pauline C Xu ◽  
Tom Thompson ◽  
So-Youn Kim
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Cancer Progression ◽  
Cancer Cachexia ◽  
Critical Role ◽  
Activin A ◽  
Adipose Tissues ◽  
Female Mice ◽  
Brown Adipose

Abstract Background: Nearly 50% of cancer patients suffer from cancer cachexia, a wasting syndrome with atrophy of white adipose tissue (WAT) and skeletal muscle. Cachexia leads to negative energy balance, limits cancer therapies, and reduces survival rate. It is characterized by body weight loss due to negative nutrients and energy balance from involuntary reduced food intake and abnormal metabolic conditions such as insulin resistance and hypertriglyceridemia. Cancer-driven factors such as activin A and IL-6 (interlukein-6) contribute to the occurrence of cachexia symptoms during cancer progression. While the importance of muscle atrophy has been emphasized in cachexia research, the underlying mechanism of adipose tissue wasting remains unclear. One proposed theory is that WAT switches to brown adipose tissue (BAT), characterized by the high expression level of UCP1 (uncoupling protein 1). Hypothesis: We hypothesize that activin A plays a critical role in adipose tissue wasting during cancer cachexia progression. Experiment: GDF9-iCre+; PIK3CA* female mice which shows cachexia symptoms in cancer progression were sacrificed before and after cachexia development. In addition, we injected FST288, an antagonist to activin A, for two weeks during cancer cachexia development. We harvested and analyzed multi-sites adipose tissues (gonadal, subcutaneous, interscapular and perirenal), muscle and liver. Serum activin A and IL-6 were measured using ELISA kits. DEXA and calorimetry analyses were performed, as well as immunohistochemistry, qPCR and western blotting assay. Results:GDF9-iCre+; PIK3CA* female mice started to display bilateral ovarian tumors around postnatal day (PD) 60, lose body weight around PD70 and became cachexia condition around PD80 with an increased level of serum activin A. Along with that, other body organs including liver, pancreas, muscle, and adipose tissues became dramatically small in mass. Our data proved that cachexia progression is correlated with the level of activin A rather than IL-6 in serum of GDF9-iCre+; PIK3CA* female mice. As serum activin A increased, adipocytes lost lipids and had distinct browning phenotypes in some adipocytes within WAT. Interestingly, calorimetry analysis did not display an increase in energy expenditure in cachectic mice although browning was evident in WAT. However, treatment with FST288 during cancer progression kept body weight and WAT in GDF9-iCre+; PIK3CA* female mice. Most of all, FST288 protected the size and lipid droplets of adipose tissues against WAT wasting during cachexia development. Conclusion: The progression of cancer cachexia impacts adipose tissues. Injection of FST288 supports the key role of activin A in the progress of cachexia. FST288 prevented adipose tissue wasting and cachexia development, revealing another evidence of the efficacy of activin A antagonist in preventing cancer cachexia development.

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