The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho； (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4； or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho； (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4； or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.本發明提供與活化FGF21介導之信號傳導之抗原結合蛋白有關或自其衍生的組合物及方法。在實施例中，抗原結合蛋白特異性結合至(i)β-Klotho；(ii)FGFR1c、FGFR2c、FGFR3c或FGFR4；或(iii)包含β-Klotho及FGFR1c、FGFR2c、FGFR3c及FGFR4中之一者的複合物。在一些實施例中，抗原結合蛋白誘導類似FGF21信號傳導。在一些實施例中，抗原結合蛋白為全人類、人類化或嵌合抗體、該等抗體之結合片段及衍生物、及特異性結合至以下之多肽：(i)β-Klotho；(ii)FGFR1c、FGFR2c、FGFR3c或FGFR4；或(iii)包含β-Klotho及FGFR1c、FGFR2c、FGFR3c及FGFR4中之一者的複合物。其他實施例提供編碼該等抗原結合蛋白及其片段及衍生物及多肽之核酸、包含該等聚核苷酸之細胞、製造該等抗原結合蛋白及其片段及衍生物及多肽之方法，及使用該等抗原結合蛋白及其片段及衍生物及多肽之方法，該等方法包括治療或診斷罹患2型糖尿病、肥胖症、NASH、代謝症候群及相關病症或病狀之個體的方法。
