RESUMO
BACKGROUND/OBJECTIVES: Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear. METHODS: We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast cells. RESULTS: In the temporal HFD settings, mice showed progressive glucose intolerance, insulin resistance, and adipose tissue senescence. Histochemistry analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and Masson's trichrome staining showed extensive collagen deposition in the 16th and 20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from eWAT revealed T-cell subsets as early-phase components and pro-inflammatory macrophages, as well as mast cells as the later phase components during obesity progression. In our therapeutic strategies, macrophage depletion by CLOD and mast stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved whole-body glucose homeostasis. In addition, mast cell stabilization also attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of mast cells over macrophages during obesity. CONCLUSION: New-generation mast cell stabilizers can be exploited for the treatment of obesity-associated metabolic complications.
Assuntos
Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Envelhecimento/patologia , Dieta Hiperlipídica , Fibrose/patologia , Mastócitos/patologia , Obesidade/imunologia , Obesidade/metabolismo , Tecido Adiposo/patologia , Animais , Modelos Animais de Doenças , Inflamação/metabolismo , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/patologiaRESUMO
Amphotericin B (AmB)-loaded poly(lactic-co-glycolic acid, PLGA) nanoparticles (NP) were prepared by solvent displacement. NP of size 160.7 +/- 10.45 nm, with a polydispersity index of 0.093 +/- 0.012 and a zeta-potential of -15.5 +/- 7.2 mV had satisfactory drug entrapment efficiency (42.5 +/- 6.41%). Biphasic drug release characterized by an initial burst followed by subsequent sustained release was observed. Applicability against visceral leishmaniasis and cancer is under investigation.
Assuntos
Implantes Absorvíveis , Anfotericina B/química , Preparações de Ação Retardada/química , Ácido Láctico/química , Nanocápsulas/química , Ácido Poliglicólico/química , Absorção , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Antifúngicos/química , Difusão , Nanocápsulas/ultraestrutura , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
Poly(lactide-co-glycolide) nanoparticles (NP) containing Doxorubicin (DOX) along with a nitric oxide (NO) donor Sodium Nitroprusside (SNP) were prepared by solvent displacement. NO is expected to synergise with antileishmanial activity of DOX. Preformulation studies showed no significant interaction between DOX and SNP. DOX and SNP loaded NP had an average size of 352 nm with 48% entrapment efficiency and a drug content of 10% w/w. Biphasic drug release was observed in vitro, with an initial burst of DOX and SNP (approximately 26% and 35% respectively) followed by sustained release for over 72 hrs.