scholarly journals Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yitong Guo ◽  
Zhuo Wan ◽  
Ping Zhao ◽  
Mengying Wei ◽  
Yunnan Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Drug Efficacy ◽  
Topical Delivery ◽  
Ultrasound Irradiation ◽  
Omental Adipose Tissue ◽  
Target Organs ◽  
Delivery Platform ◽  
Basic Characteristics

Abstract Background Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing drugs at targeted location. Results The swtichable stealth coat CP05-TK-mPEG was synthesized and anchored onto exosomes through the interaction between peptide CP05 and exosomal surface marker CD63. Chlorin e6 (Ce6) was loaded into exosomes by direct incubation. Controllable removal of PEG could be achieved by breaking thioketal (TK) through reactive oxygen species (ROS), which was produced by Ce6 under ultrasound irradiation. The whole platform was called SmartExo. The stealth effects were analyzed in RAW264.7 cells and C57BL/6 mice via tracing the exosomes. To confirm the efficacy of the engineered smart exosomes, Bone morphogenetic protein 7 (Bmp7) mRNA was encapsulated into exosomes by transfection of overexpressing plasmid, followed by stealth coating, with the exosomes designated as SmartExo@Bmp7. Therapeutic advantages of SmartExo@Bmp7 were proved by targeted delivering Bmp7 mRNA to omental adipose tissue (OAT) of obese C57BL/6 mice for browning induction. SmartExo platform was successfully constructed without changing the basic characteristics of exosomes. The engineered exosomes effectively escaped from the phagocytosis by RAW264.7 and non-target organs. In addition, the SmartExo could be uptaken locally on-demand by ultrasound mediated removal of the stealth coat. Compared with control exosomes, SmartExo@Bmp7 effectively delivered Bmp7 mRNA into OAT upon ultrasound irradiation, and induced OAT browning, as evidenced by the histology of OAT and increased expression of uncoupling protein 1 (Ucp1). Conclusions The proposed SmartExo-based delivery platform, which minimizes side effects and maximizing drug efficacy, offers a novel safe and efficient approach for targeted drug delivery. As a proof, the SmartExo@Bmp7 induced local white adipose tissue browning, and it would be a promising strategy for anti-obesity therapy. Graphical Abstract

scholarly journals Uncoupling protein-2 (UCP2) gene expression in subcutaneous and omental adipose tissue of Asian Indians

Adipocyte ◽  
2012 ◽  
Vol 1 (2) ◽  
pp. 101-107 ◽  
Author(s):  
Sujata R. Mahadik ◽  
Ramchandra D. Lele ◽  
Dhananjaya Saranath ◽  
Anika Seth ◽  
Vikram Parikh
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Asian Indians ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Omental Adipose Tissue ◽  
Ucp2 Gene

Topical Delivery of IL-10 Using a Thermosensitive Drug Delivery Platform to Treat Murine Colitis

2017 ◽  
Vol 152 (5) ◽  
pp. S567
Author(s):  
Sidhartha R. Sinha ◽  
Linh Nguyen ◽  
Anika N. Ullah ◽  
Aida Habtezion
Keyword(s):  
Drug Delivery ◽  
Topical Delivery ◽  
Murine Colitis ◽  
Delivery Platform

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

Adipose Tissue Remodeling by Prolonged Administration of High Dose of Vitamin D3 in Rats Treated to Prevent Sarcopenia

2017 ◽  
Vol 68 (9) ◽  
pp. 2139-2143 ◽  
Author(s):  
Alin Constantin Pinzariu ◽  
Sorin Aurelian Pasca ◽  
Allia Sindilar ◽  
Cristian Drochioi ◽  
Mihail Balan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D3 ◽  
Term Treatment ◽  
High Dose ◽  
Omental Adipose Tissue ◽  
Long Term Treatment ◽  
Male Wistar Rats ◽  
Adipose Tissue Remodeling ◽  
Visceral Adipose

To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.

Hydrogel-clay Nanocomposites as Carriers for Controlled Release

2020 ◽  
Vol 27 (6) ◽  
pp. 919-954 ◽  
Author(s):  
Raluca Ianchis ◽  
Claudia Mihaela Ninciuleanu ◽  
Ioana Catalina Gifu ◽  
Elvira Alexandrescu ◽  
Cristina Lavinia Nistor ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Hybrid Materials ◽  
Pharmaceutical Formulations ◽  
Tree Of Life ◽  
Present Review ◽  
Clay Nanocomposites ◽  
Delivery Platform ◽  
Complex Hybrid

The present review aims to summarize the research efforts undertaken in the last few years in the development and testing of hydrogel-clay nanocomposites proposed as carriers for controlled release of diverse drugs. Their advantages, disadvantages and different compositions of polymers/biopolymers with diverse types of clays, as well as their interactions are discussed. Illustrative examples of studies regarding hydrogel-clay nanocomposites are detailed in order to underline the progressive researches on hydrogel-clay-drug pharmaceutical formulations able to respond to a series of demands for the most diverse applications. Brief descriptions of the different techniques used for the characterization of the obtained complex hybrid materials such as: swelling, TGA, DSC, FTIR, XRD, mechanical, SEM, TEM and biology tests, are also included. Enlightened by the presented data, we can suppose that hydrogel-clay nanocomposites will still be a challenging subject of global assiduous researches. We can dare to dream to an efficient drug delivery platform for the treatment of multiple affection concomitantly, these being undoubtedly like ”a tree of life” bearing different kinds of fruits and leaves proper for human healing.

scholarly journals Systems-wide effects of short-term feed deprivation in obese mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Andersen ◽  
Henrik Munch Roager ◽  
Li Zhang ◽  
Janne Marie Moll ◽  
Henrik Lauritz Frandsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Butyric Acid ◽  
Visceral Adipose Tissue ◽  
Animal Studies ◽  
Uncoupling Protein ◽  
Metabolic Changes ◽  
Obese Mice ◽  
Short Term ◽  
Feed Deprivation ◽  
Visceral Adipose

AbstractWhile prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.

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