title: Targeted loss of GHR signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Vijayakumar
authors.forename: YingJie
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Li
authors.forename: Zuha
authors.initials: Z
authors.lastname: Jeddy
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019610:Cytoprotection / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D017353:Gene Deletion; D018390:Gene Targeting; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C051815:somatotropin-binding protein