Reduced Expression of Urokinase Plasminogen Activator in Brown Adipose Tissue of Obese Mouse Models

Published on Mar 26, 2021in International Journal of Molecular Sciences4.556
· DOI :10.3390/IJMS22073407
Chung-Ze Wu , Chung Ze Wu11
Estimated H-index: 11
(TMU: Taipei Medical University)
+ 4 AuthorsJin-Shuen Chen5
Estimated H-index: 5
(NDMC: National Defense Medical Center)
In recent decades, the obesity epidemic has resulted in morbidity and mortality rates increasing globally. In this study, using obese mouse models, we investigated the relationship among urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues. Two groups, each comprised of C57BL/6J and BALB/c male mice, were fed a chow diet (CD) and a high fat diet (HFD), respectively. Within the two HFD groups, half of each group were euthanized at 8 weeks (W8) or 16 weeks (W16). Blood, urine and adipose tissues were collected and harvested for evaluation of the effects of obesity. In both mouse models, triglyceride with insulin resistance and body weight increased with duration when fed a HFD in comparison to those in the groups on a CD. In both C57BL/6J and BALB/c HFD mice, levels of serum uPA initially increased significantly in the W8 group, and then the increment decreased in the W16 group. The glomerular filtration rate declined in both HFD groups. The expression of uPA significantly decreased in brown adipose tissue (BAT), but not in white adipose tissue, when compared with that in the CD group. The results suggest a decline in the expression of uPA in BAT in obese m models as the serum uPA increases. There is possibly an association with BAT fibrosis and dysfunction, which may need further study.
#1Martín AlcaláH-Index: 7
#2María Calderon-Dominguez (University of Barcelona)H-Index: 10
Last. Laura Herrero (University of Barcelona)H-Index: 23
view all 8 authors...
Obesity is associated with severe metabolic diseases such as type 2 diabetes, insulin resistance, cardiovascular disease and some forms of cancer. The pathophysiology of obesity-induced metabolic diseases has been strongly related to white adipose tissue (WAT) dysfunction through several mechanisms such as fibrosis, apoptosis, inflammation, ER and oxidative stress. However, little is known of whether these processes are also present in brown adipose tissue (BAT) during obesity, and the potential...
71 CitationsSource
#1Vivette D. D'Agati (CUMC: Columbia University Medical Center)H-Index: 99
#2Avry Chagnac (TAU: Tel Aviv University)H-Index: 23
Last. Manuel Praga (Complutense University of Madrid)H-Index: 49
view all 7 authors...
The incidence of obesity-related glomerulopathy (ORG) — a distinct entity featuring proteinuria, glomerulomegaly, progressive glomerulosclerosis and renal functional decline — is increasing in parallel with the obesity epidemic. Here, Vivette D'Agati and colleagues review the pathology, clinical features, treatment and pathogenesis of ORG.
214 CitationsSource
#1Yousef Fazel (Inova Health System)H-Index: 5
#2Aaron B. Koenig (Inova Health System)H-Index: 7
Last. Zobair M. Younossi (Inova Health System)H-Index: 10
view all 5 authors...
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD) that leads to progressive liver disease and presents a growing challenge to public health. Because of the increased prevalence of metabolic syndrome and obesity, NAFLD and NASH have expanded to a substantial extent. In NASH patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH is mandatory. Although there is currently n...
173 CitationsSource
#1Vanessa Pellegrinelli (University of Cambridge)H-Index: 7
#2Stefania Carobbio (University of Cambridge)H-Index: 21
Last. Antonio Vidal-Puig (University of Cambridge)H-Index: 85
view all 3 authors...
White adipose tissue (WAT) has key metabolic and endocrine functions and plays a role in regulating energy homeostasis and insulin sensitivity. WAT is characterised by its capacity to adapt and expand in response to surplus energy through processes of adipocyte hypertrophy and/or recruitment and proliferation of precursor cells in combination with vascular and extracellular matrix remodelling. However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises its f...
161 CitationsSource
#1Chung Ze Wu (TMU: Taipei Medical University)H-Index: 11
#2Li-Chien Chang (NDMC: National Defense Medical Center)H-Index: 16
Last. Jin Shuen Chen (NDMC: National Defense Medical Center)H-Index: 11
view all 7 authors...
Abstract Objectives Soluble urokinase plasminogen activator receptor (suPAR), derived from membrane bound uPAR, is associated with inflammatory diseases. In the present study, we explored the expression of uPAR/suPAR in common biopsy-proven kidney diseases and the relationship between suPAR and staging of type 2 diabetic nephropathy (DN). Design and methods Serum samples for suPAR and renal tissues for uPAR staining were investigated in various common kidney diseases. The levels of serum suPAR w...
22 CitationsSource
#1Jin Shuen Chen (NDMC: National Defense Medical Center)H-Index: 11
#2Chung Ze Wu (TMU: Taipei Medical University)H-Index: 11
Last. Yuh Feng Lin (TMU: Taipei Medical University)H-Index: 20
view all 6 authors...
We investigated the role of urokinase plasminogen activator (uPA) and its soluble receptors (suPAR) and plasminogen activator inhibitor-1 (PAI-1) in metabolic syndrome (MetS) components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship betwe...
5 CitationsSource
#1Nemanja Jovicic (University of Kragujevac)H-Index: 13
#2Ilija Jeftic (University of Kragujevac)H-Index: 7
Last. Nada Pejnovic (University of Kragujevac)H-Index: 25
view all 7 authors...
Immune reactivity plays an important role in obesity-associated metabolic disorders. We investigated immunometabolic phenotype of C57Bl/6 and BALB/c mice, prototypical Th1 and Th2-type strains, fed chow or high-fat diet (HFD) for 24 weeks. In comparison to C57Bl/6 mice, chow-fed BALB/c mice had higher body weight and weight gain, lower glycemia, more pronounced liver steatosis, but less inflammation and collagen deposition in liver. In response to HFD C57Bl/6 mice exhibited higher weight gain, h...
57 CitationsSource
#1Christa BuechlerH-Index: 42
#2Sabrina KrautbauerH-Index: 15
Last. Kristina EisingerH-Index: 11
view all 3 authors...
The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereb...
66 CitationsSource
#1Paul Trayhurn (KSU: King Saud University)H-Index: 39
#2Suliman Y. Alomar (KSU: King Saud University)H-Index: 9
Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4 and VEGF), an increase in glucose utilisation and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity ha...
42 CitationsSource
The growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention to the (patho)physiol- ogy of distinct fat depots. Brown adipose tissue (BAT), in contrast to bona fide white fat, can dissipate significant amounts of chemical energy through uncoupled respira- tion and heat production (thermogenesis). This process is mediated by the major thermogenic factor uncoupling pro- tein-1 and can be activated by certain stimuli, such ...
68 CitationsSource
Cited By0