Mi-Young Song1, Jie Wang1, Youngyi Lee1, Juhyung Lee2, Keun-Sang Kwon2, Eun Ju Bae3, Byung-Hyun Park1. 1. Department of Biochemistry Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea. 2. Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea. 3. College of Pharmacy, Woosuk University, Wanju, Jeonbuk, Republic of Korea.
Abstract
SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
SCOPE: 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. METHODS AND RESULTS:Fat-1mice 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-1mice. In flow cytometric analysis, M1 macrophage infiltration into adipose tissue was markedly attenuated in fat-1mice. 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. CONCLUSION: 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.
Authors: Natalie M Hohos; Kirstin J Cho; Delaney C Swindle; Amanda A Allshouse; Michael C Rudolph; Malgorzata E Skaznik-Wikiel Journal: Endocrinology Date: 2018-12-01 Impact factor: 4.736
Authors: Beatriz Burger; Carolina M C Kühl; Thamiris Candreva; Renato da S Cardoso; Jéssica R Silva; Bianca G Castelucci; Sílvio R Consonni; Helena L Fisk; Philip C Calder; Marco Aurélio R Vinolo; Hosana G Rodrigues Journal: Sci Rep Date: 2019-06-24 Impact factor: 4.379