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Updated: Feb 25, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Blockade of myeloid differentiation protein 2 prevents obesity-induced inflammation and nephropathy
Qilu Fang1,2, Lintao Wang1, Daona Yang2
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Abstract:
Obesity is a major and independent risk factor of kidney diseases. The pathogenic mechanisms of obesity-associated renal injury are recognized to at least involve a lipid-rich and pro-inflammatory state of the renal tissues, but specific mechanisms establishing causal relation remain unknown. Saturated fatty acids are elevated in obesity, and known to induce chronic inflammation in kidneys. Myeloid differentiation protein 2 (MD2) is an important protein in lipopolysaccharide-induced innate immunity response and inflammation. We suggested that obesity-associated renal injury is regulated by MD2 thereby driving an inflammatory renal injury. The used three mouse models for in vivo study: MD2 knockout mice (KO) maintained on high fat diet (HFD), wild-type mice on HFD plus L6H21, a specific MD2 inhibitor and KO mice given palmitic acid (PA) by IV injection. The in vitro studies were carried out in cultured renal tubular epithelial cells, mouse mesangial cells and primary macrophages, respectively. The HFD mice presented with increased hyperlipidemia, serum creatinine and proteinuria. Renal tissue from HFD mice had increased fibrosis, inflammatory cytokines, macrophage infiltration, and activation of NF-κB and MAPKs. This HFD-induced renal injury profile was not observed in KO mice or L6H21-treated mice. Mice given PA mimmicked the HFD-induced renal injury profiles, which were prevented by MD2 knockout. The in vitro data further confirmed MD2 mediates PA-induced inflammation. MD2 is causally related with obesity-associated renal inflammatory injury. We believe that MD2 is an attractive target for future therapeutic strategies in obesity-associated kidney diseases.
Insights
Obesity drives kidney inflammation and injury through Myeloid Differentiation protein 2 (MD2). Inhibiting MD2 or its activation by fatty acids like palmitic acid protects against obesity-related kidney damage.
Area of Science:
- Nephrology
- Immunology
- Metabolic Diseases
Background:
- Obesity is a significant risk factor for kidney disease, characterized by inflammation and lipid accumulation in renal tissues.
- The precise mechanisms linking obesity to kidney injury remain unclear, despite the known role of saturated fatty acids in promoting kidney inflammation.
Purpose of the Study:
- To investigate the role of Myeloid Differentiation protein 2 (MD2) in obesity-associated kidney inflammation and injury.
- To determine if MD2 mediates the inflammatory effects of saturated fatty acids in the kidney.
Main Methods:
- In vivo studies utilized high-fat diet (HFD) fed MD2 knockout (KO) mice, wild-type mice treated with an MD2 inhibitor (L6H21), and KO mice injected with palmitic acid (PA).
- In vitro studies involved cultured renal tubular epithelial cells, mesangial cells, and macrophages to assess MD2-mediated inflammation.
Main Results:
- HFD-induced obesity in mice led to hyperlipidemia, elevated creatinine, proteinuria, renal fibrosis, and increased inflammatory markers.
- MD2 knockout or inhibition prevented these HFD-induced renal injury markers.
- Palmitic acid administration mimicked HFD-induced renal injury, an effect abolished by MD2 knockout, confirming MD2's role in mediating fatty acid-induced inflammation.
Conclusions:
- Myeloid Differentiation protein 2 (MD2) plays a causal role in obesity-associated renal inflammatory injury.
- MD2 mediates inflammation induced by saturated fatty acids, such as palmitic acid, in the kidney.
- Targeting MD2 presents a potential therapeutic strategy for managing obesity-related kidney diseases.
