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Grb7 Ablation in Mice Improved Glycemic Control, Enhanced Insulin Signaling, and Increased Abdominal fat Mass in Females.
Vermehren-Schmaedick, Anke; Joshi, Sonali; Wagoner, Wendy; Norgard, Mason A; Packwood, William; Diba, Parham; Mendez, Heike; Fedorov, Lev M; Rakshe, Shauna; Park, Byung; Marks, Daniel L; Grossberg, Aaron; Luoh, Shiuh-Wen.
Afiliación
  • Vermehren-Schmaedick A; Veterans Administration Portland Health Care System, Division of Hospital and Specialty Medicine, Portland, OR 97239, USA.
  • Joshi S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Wagoner W; Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Norgard MA; Veterans Administration Portland Health Care System, Division of Hospital and Specialty Medicine, Portland, OR 97239, USA.
  • Packwood W; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Oregon Health & Science University and Knight Cancer Institute, Portland, OR 97239, USA.
  • Diba P; Veterans Administration Portland Health Care System, Division of Hospital and Specialty Medicine, Portland, OR 97239, USA.
  • Mendez H; Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239, USA.
  • Fedorov LM; Small Animal Research Imaging Core, USR Program, Oregon Health & Science University, Portland, OR 97239, USA.
  • Rakshe S; Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239, USA.
  • Park B; Medical Scientist Training Program, Oregon Health & Science University, Portland, OR 97239, USA.
  • Marks DL; Brenden Colson Center for Pancreatic Care, Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Grossberg A; Transgenic Mouse Models Shared Resource, USR Program, Oregon Health & Science University, Portland, OR 97239, USA.
  • Luoh SW; Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Endocrinology ; 165(5)2024 Mar 29.
Article en En | MEDLINE | ID: mdl-38578949
ABSTRACT

OBJECTIVES:

Growth factor receptor bound protein 7 (GRB7) is a multidomain signaling adaptor. Members of the Grb7/10/14 family, specifically Gbrb10/14, have important roles in metabolism. We ablated the Grb7 gene in mice to examine its metabolic function.

METHODS:

Global ablation of Grb7 in FVB/NJ mice was generated. Growth, organ weight, food intake, and glucose homeostasis were measured. Insulin signaling was examined by Western blotting. Fat and lean body mass was measured by nuclear magnetic resonance, and body composition after fasting or high-fat diet was assessed. Energy expenditure was measured by indirect calorimetry. Expression of adiposity and lipid metabolism genes was measured by quantitative PCR.

RESULTS:

Grb7-null mice were viable, fertile, and without obvious phenotype. Grb7 ablation improved glycemic control and displayed sensitization to insulin signaling in the liver. Grb7-null females but not males had increased gonadal white adipose tissue mass. Following a 12-week high-fat diet, Grb7-null female mice gained fat body mass and developed relative insulin resistance. With fasting, there was less decrease in fat body mass in Grb7-null female mice. Female mice with Grb7 ablation had increased baseline food intake, less energy expenditure, and displayed a decrease in the expression of lipolysis and adipose browning genes in gonadal white adipose tissue by transcript and protein analysis.

CONCLUSION:

Our study suggests that Grb7 is a negative regulator of glycemic control. Our results reveal a role for Grb7 in female mice in the regulation of the visceral adipose tissue mass, a powerful predictor of metabolic dysfunction in obesity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Ratones Noqueados / Metabolismo Energético / Grasa Abdominal / Proteína Adaptadora GRB7 / Insulina Límite: Animals Idioma: En Revista: Endocrinology Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Ratones Noqueados / Metabolismo Energético / Grasa Abdominal / Proteína Adaptadora GRB7 / Insulina Límite: Animals Idioma: En Revista: Endocrinology Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos