Related Experiment Video
Updated: Aug 28, 2025
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Tangeretin protects mice from diet-induced metabolic inflammation via activating adipose lactate accumulation and
Yulin Sun1, Lu Liu2, Chen Qiu1
1Key Laboratory of the Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing, 211166, China.
Abstract:
Infiltration by adipose tissue macrophages (ATMs) and subsequent metabolic inflammation are the key causes of obesity-induced insulin resistance and metabolic disorders. In this study, we analyzed the potential protective effect of tangeretin, a key flavonoid found extensively in citrus peels, against diet-induced metabolic inflammation. Daily gavages of tangeretin at 20 mg/kg protected the mice from high fat diet (HFD) feeding-induced insulin resistance, ATMs activation, and M1 macrophage polarization. Interestingly, in vitro assays using bone marrow-derived macrophages (BMDMs) showed that tangeretin had only a minimal effect on macrophage polarization. Assays of central carbon metabolism (CCM) in adipose tissue showed that tangeretin treatment rerouted the carbon metabolism and caused lactate accumulation in the microenvironment. Co-culture assays further suggested that tangeretin enhanced M2 polarization of BMDMs when adipocytes were present, whereas blocking the lactate uptake in macrophages reversed the effect of tangeretin on polarization. Taken together, these findings indicated that tangeretin provided indirect protection from diet-induced ATMs activation by reprogramming glucose metabolism and promoting lactate accumulation that subsequently promoted macrophage M2 polarization and reduced inflammation.
Insights
Tangeretin, a citrus flavonoid, combats obesity-induced inflammation by reprogramming glucose metabolism. It promotes lactate accumulation, enhancing M2 macrophage polarization and reducing insulin resistance.
Area of Science:
- Metabolic inflammation
- Obesity research
- Immunometabolism
Background:
- Adipose tissue macrophages (ATMs) drive obesity-related insulin resistance and metabolic dysfunction.
- Metabolic inflammation is a key pathological feature of obesity.
Purpose of the Study:
- To investigate the protective effects of tangeretin against diet-induced metabolic inflammation.
- To elucidate the mechanisms underlying tangeretin's action on macrophages and metabolism.
Main Methods:
- Mice were fed a high-fat diet (HFD) and treated with tangeretin.
- In vitro assays using bone marrow-derived macrophages (BMDMs) and adipocytes.
- Analysis of central carbon metabolism (CCM) in adipose tissue.
- Macrophage polarization assays and lactate uptake experiments.
Main Results:
- Tangeretin treatment protected mice from HFD-induced insulin resistance, ATM activation, and M1 macrophage polarization.
- Tangeretin rerouted CCM in adipose tissue, leading to lactate accumulation.
- Tangeretin promoted M2 macrophage polarization indirectly through lactate, particularly in the presence of adipocytes.
Conclusions:
- Tangeretin offers indirect protection against diet-induced ATM activation.
- The mechanism involves reprogramming glucose metabolism, increasing lactate, and promoting M2 macrophage polarization.
- Tangeretin represents a potential therapeutic strategy for metabolic disorders associated with obesity.
