scholarly journals WAT’s up!? – Organ-on-a-chip integrating human mature white adipose tissues for mechanistic research and pharmaceutical applications

2019 ◽  
Author(s):  
Julia Rogal ◽  
Carina Binder ◽  
Elena Kromidas ◽  
Christopher Probst ◽  
Stefan Schneider ◽  
...  
Keyword(s):  
Animal Models ◽  
Metabolic Diseases ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Promising Tool ◽  
Global Pandemic ◽  
Microfluidic Perfusion ◽  
Obesity And Diabetes ◽  
Organ On A Chip ◽  
Media Channels

AbstractObesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAT) – a key contributor in many metabolic diseases – contributes about one fourth of a healthy human’s body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human WAT. The WAT-on-a-chip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform’s capability to maintain long-term viability and functionality of WAT was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.

scholarly journals Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

2013 ◽  
Vol 305 (3) ◽  
pp. E439-E450 ◽  
Author(s):  
Ping Kong ◽  
Carlos Gonzalez-Quesada ◽  
Na Li ◽  
Michele Cavalera ◽  
Dong-Wook Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Uptake ◽  
Cytokine Signaling ◽  
Vascular Density ◽  
Acid Uptake ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes.

scholarly journals Recent Update on the Molecular Mechanisms of Gonadal Steroids Action in Adipose Tissue

2021 ◽  
Vol 22 (10) ◽  
pp. 5226
Author(s):  
Agata Wawrzkiewicz-Jałowiecka ◽  
Anna Lalik ◽  
Graça Soveral
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Fatty Acid Uptake ◽  
Gonadal Steroids ◽  
Acid Uptake ◽  
Metabolic Disturbances ◽  
Fat Depots

The gonadal steroids, including androgens, estrogens and progestogens, are involved in the control of body fat distribution in humans. Nevertheless, not only the size and localization of the fat depots depend on the sex steroids levels, but they can also highly affect the functioning of adipose tissue. Namely, the gonadocorticoids can directly influence insulin signaling, lipid metabolism, fatty acid uptake and adipokine production. They may also alter energy balance and glucose homeostasis in adipocytes in an indirect way, e.g., by changing the expression level of aquaglyceroporins. This work presents the recent advances in understanding the molecular mechanism of how the gonadal steroids influence the functioning of adipose tissue leading to a set of detrimental metabolic consequences. Special attention is given here to highlighting the sexual dimorphism of adipocyte functioning in terms of health and disease. Particularly, we discuss the molecular background of metabolic disturbances occurring in consequence of hormonal imbalance which is characteristic of some common endocrinopathies such as the polycystic ovary syndrome. From this perspective, we highlight the potential drug targets and the active substances which can be used in personalized sex-specific management of metabolic diseases, in accord with the patient’s hormonal status.

scholarly journals Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4394 ◽  
Author(s):  
Kitamura
Keyword(s):  
Animal Models ◽  
Metabolic Diseases ◽  
Living Environment ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Propolis Extract ◽  
Beneficial Effects ◽  
Cellular Models ◽  
Molecular Events ◽  
Obesity And Diabetes

Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.

scholarly journals Annexins in Adipose Tissue: Novel Players in Obesity

2019 ◽  
Vol 20 (14) ◽  
pp. 3449 ◽  
Author(s):  
Thomas Grewal ◽  
Carlos Enrich ◽  
Carles Rentero ◽  
Christa Buechler
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Transporter ◽  
Metabolic Diseases ◽  
Cell Metabolism ◽  
Fatty Acid Uptake ◽  
Membrane Microdomains ◽  
Acid Uptake ◽  
Dependent Manner ◽  
Membrane Microdomain

Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca2+)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.

Unaltered Fatty Acid Uptake, Utilization, and Mitochondrial Respiration in Right Atrial Appendage of Type 2 Diabetic Human Heart

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 335-OR
Author(s):  
NANDINI RJ ◽  
SR RAJI ◽  
VIVEK V. PILLAI ◽  
JAYAKUMAR K. ◽  
SRINIVAS GOPALA
Keyword(s):  
Fatty Acid ◽  
Mitochondrial Respiration ◽  
Human Heart ◽  
Fatty Acid Uptake ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Acid Uptake ◽  
Right Atrial Appendage ◽  
Type 2 Diabetic

scholarly journals Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

2021 ◽  
Author(s):  
Longmin Chen ◽  
Jing Zhang ◽  
Yuan Zou ◽  
Faxi Wang ◽  
Jingyi Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
Fatty Acid Uptake ◽  
Chromatin Accessibility ◽  
Acid Uptake ◽  
High Fat ◽  
M2 Polarization ◽  
Adipose Tissue Macrophages ◽  
Cold Challenge

AbstractKdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2af/f, Kdm2a−/−) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a−/− increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a−/− mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a−/− macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a−/− mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.

scholarly journals Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Fatty Acid Uptake ◽  
Isoquinoline Alkaloid ◽  
Acid Uptake ◽  
High Fat ◽  
Low Fat

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.

Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid

Diabetes ◽  
1999 ◽  
Vol 48 (6) ◽  
pp. 1245-1250 ◽  
Author(s):  
A. K. Turpeinen ◽  
T. O. Takala ◽  
P. Nuutila ◽  
T. Axelin ◽  
M. Luotolahti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Heptadecanoic Acid
Sign in / Sign up

Export Citation Format

Share Document