1. ILC2s Improve Glucose Metabolism Through the Control of Saturated Fatty Acid Absorption Within Visceral Fat.
- Author
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Okamura T, Hashimoto Y, Mori J, Yamaguchi M, Majima S, Senmaru T, Ushigome E, Nakanishi N, Asano M, Yamazaki M, Takakuwa H, Satoh T, Akira S, Hamaguchi M, and Fukui M
- Subjects
- Absorption, Physiological, Adoptive Transfer, Animals, Blood Glucose drug effects, CD36 Antigens metabolism, Glucose Intolerance drug therapy, Glucose Intolerance genetics, Glucose Intolerance immunology, Homeostasis, Inflammation immunology, Inflammation metabolism, Inflammation Mediators metabolism, Interleukin-1 Receptor-Like 1 Protein genetics, Interleukin-1 Receptor-Like 1 Protein metabolism, Interleukin-33 pharmacology, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat immunology, Lymphocytes drug effects, Lymphocytes immunology, Macrophages immunology, Macrophages metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Obesity immunology, Obesity metabolism, RAW 264.7 Cells, Blood Glucose metabolism, Fatty Acids metabolism, Glucose Intolerance metabolism, Immunity, Innate drug effects, Insulin Resistance, Intra-Abdominal Fat metabolism, Lymphocytes metabolism
- Abstract
Background and Aims: Group 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis in mice., Methods: In this study, the role of ILC2s in white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout mice., Results: The deficiency of ST2 decreased ILC2s in WAT, whereas ex-ILC2, which acquired group 1 innate lymphoid cell (ILC1)-like traits, was increased. This led to significant metabolic disorders such as visceral fat obesity, decreased browning in WAT, reduction of energy metabolism, and impaired glucose tolerance, compared to wild type (WT) mice. Those metabolic abnormalities of ST2-knockout (ST2KO) mice were not ameliorated by IL-33 administration, but impaired glucose tolerance and visceral fat obesity were significantly improved by transplantation of ILCs from the bone marrow of WT mice. The relative expression of Cd36 in WAT increased due to the deficiency of ST2, and the storage of saturated fatty acids in WAT of ST2KO mice was significantly higher than that of WT mice. Moreover, saturated fatty acids aggravated the chronic inflammation in adipocytes, promoted the differentiation of M1-like macrophages, and inhibited that of M2-like macrophages., Conclusions: Our results indicated that ILC2 regulates diet-induced obesity and chronic inflammation through the regulation of saturated fatty acid absorption in visceral adipose tissue., Competing Interests: Author HT was employed by the company Agilent Technologies. YH has received grants from Asahi Kasei Pharma, personal fees from Daiichi Sankyo Co., Ltd., personal fees from Mitsubishi Tanabe Pharma Corp., personal fees from Sanofi K.K., personal fees from Novo Nordisk Pharma Ltd., outside the submitted work. TSe has received personal fees from Ono Pharma Co., Ltd., Mitsubishi Tanabe Pharma Co, Astellas Pharma Inc., Kyowa Hakko Kirin Co., Ltd., Sanofi K.K., MSD K.K., Kowa Pharma Co., Ltd., Taisho Toyama Pharma Co., Ltd., Takeda Pharma Co., Ltd., Kissei Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K. outside the submitted work. EU has received grants from the Japanese Study Group for Physiology and Management of Blood Pressure, the Astellas Foundation for Research on Metabolic Disorders (Grant number: 4024). Donated Fund Laboratory of Diabetes therapeutics is an endowment department, supported with an unrestricted grant from Ono Pharmaceutical Co., Ltd., and received personal fees from AstraZeneca plc, Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Kyowa Hakko Kirin Company Ltd., Kowa Pharmaceutical Co., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corp., Novo Nordisk Pharma Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd., outside the submitted work. MH has received grants from Asahi Kasei Pharma, Nippon Boehringer Ingelheim Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., and Eli Lilly Japan K.K., outside the submitted work. MA received personal fees from Novo Nordisk Pharma Ltd., Abbott Japan Co., Ltd., AstraZeneca plc, Kowa Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., outside the submitted work. MaY reports personal fees from MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Kowa Company, Limited, AstraZeneca PLC, Takeda Pharmaceutical Company Limited, Kyowa Hakko Kirin Co., Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co., Ltd., Ono Pharma Co., Ltd., outside the submitted work. Michiaki Fukui has received grants from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharma Co., Ltd., Mitsubishi Tanabe Pharma Co, Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharma Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd. Eli Lilly Japan K.K., Taisho Pharma Co., Ltd., Terumo Co., Teijin Pharma Ltd., Nippon Chemiphar Co., Ltd., and Johnson & Johnson K.K. Medical Co., Abbott Japan Co., Ltd., and received personal fees from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharma Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Eli Lilly Japan K.K., Taisho Pharma Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharma Co., Ltd., Abbott Japan Co., Ltd., Medtronic Japan Co., Ltd., Arkley Inc., Teijin Pharma Ltd. and Nipro Cor., outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Okamura, Hashimoto, Mori, Yamaguchi, Majima, Senmaru, Ushigome, Nakanishi, Asano, Yamazaki, Takakuwa, Satoh, Akira, Hamaguchi and Fukui.)
- Published
- 2021
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