title: MAP4K4 and IL-6+Th17 cells play important roles in non-obese type 2 diabetes.
abstract: Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6+Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.
authors.affiliation: Immunology Research Center, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan.
authors.forename: Huai-Chia
authors.initials: HC
authors.lastname: Chuang
authors.affiliation: Immunology Research Center, National Health Research Institutes, 35 Keyan Road, Zhunan, 35053, Taiwan. ttan@nhri.org.tw.|Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, 77030, USA. ttan@nhri.org.tw.
authors.forename: Tse-Hua
authors.initials: TH
authors.lastname: Tan
mesh_terms: D000818:Animals; D001208:Asia; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000276:immunology*; D005060:Europe; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Lean type 2 diabetes; MAP4K4; Non-obese type 2 diabetes; Normal-weight type 2 diabetes; Th17 cells; Type 2 diabetes; Visceral fat accumulation