Loss of Adipose GHR in Mice Enhances Local Fatty Acid Trapping and Impairs BAT Thermogenesis
44 Pages Posted: 9 Feb 2019 Publication Status: PublishedMore...
Growth hormone (GH) binds to its receptor GHR to exert its pleiotropic effects on growth and metabolism. Disproportionate GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific GHR deficiency and clinical observations. Here we constructed an adipose-specific GHR knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose GHR accelerated the dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing BAT burning and WAT browning induced by cold were retarded in absence of adipose GHR but was recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signalling emulates a healthy obesity situation which has metabolic advantages against HFD.
Keywords: GHR, Adipose tissues specific knockout, Lipid metabolism, Thermogenesis, Stromal vascular fractions
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