Anke Vermehren-Schmaedick, Sonali Joshi, Wendy Wagoner, Mason A. Norgard, William Packwood, Parham Diba, Heike Mendez, Lev M Fedorov, Shauna Rakshe, Byung Park, Daniel L Marks, A. Grossberg, S. Luoh
{"title":"在小鼠体内消融 Grb7 可改善血糖控制、增强胰岛素信号传导并增加雌性小鼠的腹部脂肪量。","authors":"Anke Vermehren-Schmaedick, Sonali Joshi, Wendy Wagoner, Mason A. Norgard, William Packwood, Parham Diba, Heike Mendez, Lev M Fedorov, Shauna Rakshe, Byung Park, Daniel L Marks, A. Grossberg, S. Luoh","doi":"10.1210/endocr/bqae045","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\nGrowth Factor Receptor Bound Protein 7 (GRB7) is a multi-domain 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.\n\n\nMETHODS\nGlobal 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 qPCR.\n\n\nRESULTS\nGrb7-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.\n\n\nCONCLUSIONS\nOur 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.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Grb7 ablation in mice improved glycemic control, enhanced insulin signaling and increased abdominal fat mass in females.\",\"authors\":\"Anke Vermehren-Schmaedick, Sonali Joshi, Wendy Wagoner, Mason A. Norgard, William Packwood, Parham Diba, Heike Mendez, Lev M Fedorov, Shauna Rakshe, Byung Park, Daniel L Marks, A. Grossberg, S. Luoh\",\"doi\":\"10.1210/endocr/bqae045\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE\\nGrowth Factor Receptor Bound Protein 7 (GRB7) is a multi-domain 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.\\n\\n\\nMETHODS\\nGlobal 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 qPCR.\\n\\n\\nRESULTS\\nGrb7-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.\\n\\n\\nCONCLUSIONS\\nOur 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.\",\"PeriodicalId\":11819,\"journal\":{\"name\":\"Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1210/endocr/bqae045\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/endocr/bqae045","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Grb7 ablation in mice improved glycemic control, enhanced insulin signaling and increased abdominal fat mass in females.
OBJECTIVE
Growth Factor Receptor Bound Protein 7 (GRB7) is a multi-domain 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 qPCR.
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.
CONCLUSIONS
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.
期刊介绍:
The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.