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Epiregulin as an Alternative Ligand for Leptin Receptor Alleviates Glucose Intolerance without Change in Obesity.
Song, No-Joon; Lee, Aejin; Yasmeen, Rumana; Shen, Qiwen; Yang, Kefeng; Kumar, Shashi Bhushan; Muhanna, Danah; Arnipalli, Shanvanth; Noria, Sabrena F; Needleman, Bradley J; Hazey, Jeffrey W; Mikami, Dean J; Ortega-Anaya, Joana; Jiménez-Flores, Rafael; Prokop, Jeremy; Ziouzenkova, Ouliana.
Afiliación
  • Song NJ; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Lee A; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Yasmeen R; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Shen Q; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Yang K; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Kumar SB; Department of Nutrition, School of Medical, Shanghai Jiao Tong University, Shanghai 200025, China.
  • Muhanna D; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Arnipalli S; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Noria SF; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
  • Needleman BJ; Division of General and Gastrointestinal Surgery, Center for Minimally Invasive Surgery, The Ohio State University, Columbus, OH 43210, USA.
  • Hazey JW; Division of General and Gastrointestinal Surgery, Center for Minimally Invasive Surgery, The Ohio State University, Columbus, OH 43210, USA.
  • Mikami DJ; Department of Surgery, The Ohio State University, Columbus, OH 43210, USA.
  • Ortega-Anaya J; Department of Surgery, University of Hawaii, Honolulu, HI 96813, USA.
  • Jiménez-Flores R; Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA.
  • Prokop J; Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA.
  • Ziouzenkova O; Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Cells ; 11(3)2022 01 26.
Article en En | MEDLINE | ID: mdl-35159237
The leptin receptor (LepR) acts as a signaling nexus for the regulation of glucose uptake and obesity, among other metabolic responses. The functional role of LepR under leptin-deficient conditions remains unclear. This study reports that epiregulin (EREG) governed glucose uptake in vitro and in vivo in Lepob mice by activating LepR under leptin-deficient conditions. Single and long-term treatment with EREG effectively rescued glucose intolerance in comparative insulin and EREG tolerance tests in Lepob mice. The immunoprecipitation study revealed binding between EREG and LepR in adipose tissue of Lepob mice. EREG/LepR regulated glucose uptake without changes in obesity in Lepob mice via mechanisms, including ERK activation and translocation of GLUT4 to the cell surface. EREG-dependent glucose uptake was abolished in Leprdb mice which supports a key role of LepR in this process. In contrast, inhibition of the canonical epidermal growth factor receptor (EGFR) pathway implicated in other EREG responses, increased glucose uptake. Our data provide a basis for understanding glycemic responses of EREG that are dependent on LepR unlike functions mediated by EGFR, including leptin secretion, thermogenesis, pain, growth, and other responses. The computational analysis identified a conserved amino acid sequence, supporting an evolutionary role of EREG as an alternative LepR ligand.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intolerancia a la Glucosa / Receptores de Leptina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intolerancia a la Glucosa / Receptores de Leptina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza