Glucan-Encapsulated siRNA Particles (GeRPs) for Specific Gene Silencing in Adipose Tissue Macrophages

AbstractPro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.

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Leptin in the regulation of the immunometabolism of adipose tissue‐macrophages

Journal of Leukocyte Biology ◽

10.1002/jlb.mr1218-478r ◽

2019 ◽

Vol 106 (3) ◽

pp. 703-716 ◽

Cited By ~ 16

Author(s):

Lauar Monteiro ◽

Jéssica Aparecida da Silva Pereira ◽

Lohanna Palhinha ◽

Pedro Manoel M. Moraes‐Vieira

Keyword(s):

Adipose Tissue ◽

Adipose Tissue Macrophages

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High-throughput vectors for efficient gene silencing in plants

Functional Plant Biology ◽

10.1071/fp02033 ◽

2002 ◽

Vol 29 (10) ◽

pp. 1217 ◽

Cited By ~ 99

Author(s):

Chris A. Helliwell ◽

S. Varsha Wesley ◽

Anna J. Wielopolska ◽

Peter M. Waterhouse

Keyword(s):

Gene Silencing ◽

Insertional Mutagenesis ◽

Single Step ◽

Plant Genome ◽

Specific Gene ◽

Single Polymerase Chain Reaction ◽

Efficient Gene ◽

Gene Redundancy ◽

Endogenous Genes ◽

Rapid Generation

A major challenge in the post-genome era of plant biology is to determine the functions of all genes in the plant genome. A straightforward approach to this problem is to reduce or knockout expression of a gene with the hope of seeing a phenotype that is suggestive of its function. Insertional mutagenesis is a useful tool for this type of study but is limited by gene redundancy, lethal knockouts, non-tagged mutants, and the inability to target the inserted element to a specific gene. The efficacy of gene silencing in plants using inverted-repeat transgene constructs that encode a hairpin RNA (hpRNA) has been demonstrated by a number of groups, and has several advantages over insertional mutagenesis. In this paper we describe two improved pHellsgate vectors that facilitate rapid generation of hpRNA-encoding constructs. pHellsgate 4 allows the production of an hpRNA construct in a single step from a single polymerase chain reaction product, while pHellsgate 8 requires a two-step process via an intermediate vector. We show that these vectors are effective at silencing three endogenous genes in Arabidopsis, FLOWERING LOCUS C, PHYTOENE DESATURASE and ETHYLENE INSENSITIVE 2. We also show that a construct of sequences from two genes silences both genes.

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