Targeted Loss of GHR Signaling in Mouse Skeletal Muscle Protects Against High-Fat Diet–Induced Metabolic Deterioration
| Autor: | Zuha Jeddy, Hui Sun, Archana Vijayakumar, Xiaosong Li, Yingjie Wu, Shoshana Yakar, Chengyu Liu, Derek LeRoith, Gary J. Schwartz |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Adipose tissue 030209 endocrinology & metabolism Growth hormone receptor Myostatin Biology Diet High-Fat Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Metabolic Diseases Internal medicine Internal Medicine medicine Animals Obesity Muscle Skeletal SOCS2 030304 developmental biology Mice Knockout 2. Zero hunger 0303 health sciences Skeletal muscle Receptor Cross-Talk medicine.disease Mice Inbred C57BL Metabolism Endocrinology Cytokine medicine.anatomical_structure Cytoprotection Gene Targeting biology.protein Insulin Resistance Signal transduction Carrier Proteins Gene Deletion Signal Transduction |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Growth hormone (GH) exerts diverse tissue-specific metabolic effects that are not revealed by global alteration of GH action. To study the direct metabolic effects of GH in the muscle, we specifically inactivated the growth hormone receptor (ghr) gene in postnatal mouse skeletal muscle using the Cre/loxP system (mGHRKO model). The metabolic state of the mGHRKO mice was characterized under lean and obese states. High-fat diet feeding in the mGHRKO mice was associated with reduced adiposity, improved insulin sensitivity, lower systemic inflammation, decreased muscle and hepatic triglyceride content, and greater energy expenditure compared with control mice. The obese mGHRKO mice also had an increased respiratory exchange ratio, suggesting increased carbohydrate utilization. GH-regulated suppressor of cytokine signaling-2 (socs2) expression was decreased in obese mGHRKO mice. Interestingly, muscles of both lean and obese mGHRKO mice demonstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a possible mechanism whereby GHR signaling in muscle could affect liver and adipose tissue function. Thus, our study implicates skeletal muscle GHR signaling in mediating insulin resistance in obesity and, more importantly, reveals a novel role of muscle GHR signaling in facilitating cross-talk between muscle and other metabolic tissues. |
| Databáze: | OpenAIRE |
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