Myeloid-Cell Protein Tyrosine Phosphatase-1B Deficiency in Mice Protects Against High-Fat Diet and Lipopolysaccharide-Induced Inflammation, Hyperinsulinemia, and Endotoxemia Through an IL-10 STAT3-Dependent Mechanism
Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity.
Pharmacology, Toxicology and Pharmaceutical Science
8
11%
Medicine and Dentistry
7
10%
Immunology and Microbiology
6
8%
Biochemistry, Genetics and Molecular Biology
5
7%
Other
6
8%
Unknown
23
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 December 2023.
All research outputs
#4,181,090
of 25,059,640 outputs
Outputs from Diabetes
#2,024
of 9,713 outputs
Outputs of similar age
#47,048
of 317,494 outputs
Outputs of similar age from Diabetes
#23
of 112 outputs
Altmetric has tracked 25,059,640 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,713 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,494 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 112 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
