Enhanced M2 macrophage polarization in high n-3 polyunsaturated fatty acid transgenic mice fed a high-fat diet.
Diet-induced obesity and consequent insulin resistance are caused, in part, by macrophage polarization and accumulation in peripheral tissues. Here, we examined the effects of endogenously synthesized n-3 PUFAs on macrophage chemotaxis and polarization.



Fat-1 mice and wild-type (WT) littermates were fed a 60% calorie high-fat diet (HFD) for 10 weeks. Bone marrow macrophages (BMMs) from fat-1 and WT mice were used in in vitro chemotaxis assays and macrophage polarization studies. WT mice fed a HFD exhibited glucose intolerance, insulin resistance, and lipid accumulation and macrophage infiltration in liver and adipose tissue. However, these metabolic and inflammatory phenotypes were not observed in HFD-fed fat-1 mice. In flow cytometric analysis, M1 macrophage infiltration into adipose tissue was markedly attenuated in fat-1 mice. Consistently, results from in vitro experiments indicated that n-3 PUFAs prevented adipocyte conditioned medium-mediated macrophage chemotaxis, stimulated M2 polarization, and suppressed M1 polarization. The inhibition of macrophage migration by n-3 PUFAs was associated with suppression of multiple kinases, such as IκB kinase, AKT, and focal adhesion kinase.



Our results indicate that n-3 PUFAs play a crucial role in macrophage polarization and chemotaxis, and thus regulate the development of HFD-induced tissue inflammation and metabolic derangements.
Department of Biochemistry Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Mi-Young
MY
Song
Department of Biochemistry Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Jie
J
Wang
Department of Biochemistry Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Youngyi
Y
Lee
Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Juhyung
J
Lee
Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Keun-Sang
KS
Kwon
College of Pharmacy, Woosuk University, Wanju, Jeonbuk, Republic of Korea.
Eun Ju
EJ
Bae
Department of Biochemistry Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Byung-Hyun
BH
Park
D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated
Chemotaxis; Inflammation; Macrophage; Polarization; n-3 PUFAs