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Macrophage CREBZF Orchestrates Inflammatory Response to Potentiate Insulin Resistance and Type 2 Diabetes.
Liu, Yuxiao; Su, Weitong; Liu, Zhengshuai; Hu, Zhimin; Shen, Jiaxin; Zheng, Zengpeng; Ding, Dong; Huang, Wei; Li, Wenjing; Cai, Genxiang; Wei, Shuang; Li, Ni; Fang, Xia; Li, Hong; Qin, Jun; Zhang, Haibing; Xiao, Yichuan; Bi, Yan; Cui, Aoyuan; Zhang, Chunxiang; Li, Yu.
Afiliación
  • Liu Y; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Su W; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Liu Z; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Hu Z; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Shen J; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Zheng Z; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Ding D; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Huang W; Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, China.
  • Li W; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Cai G; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Wei S; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Li N; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Fang X; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Li H; Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, China.
  • Qin J; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Zhang H; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Xiao Y; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Bi Y; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Cui A; Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China.
  • Zhang C; CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Li Y; Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education, Southwest Medical University, Luzhou, 646000, China.
Adv Sci (Weinh) ; 11(13): e2306685, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38286660
ABSTRACT
Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition-induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet-induced insulin-resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF-κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Diabetes Mellitus Tipo 2 / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Diabetes Mellitus Tipo 2 / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China