title: Metabolic effects of intra-abdominal fat in GHRKO mice.
abstract: Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are growth hormone (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate the unexpected coexistence of adiposity with improved insulin sensitivity and extended longevity, we examined effects of surgical removal of visceral (epididymal and perinephric) fat on metabolic traits related to insulin signaling and longevity. Comparison of results obtained in GHRKO mice and in normal animals from the same strain revealed disparate effects of visceral fat removal (VFR) on insulin and glucose tolerance, adiponectin levels, accumulation of ectopic fat, phosphorylation of insulin signaling intermediates, body temperature, and respiratory quotient (RQ). Overall, VFR produced the expected improvements in insulin sensitivity and reduced body temperature and RQ in normal mice and had opposite effects in GHRKO mice. Some of the examined parameters were altered by VFR in opposite directions in GHRKO and normal mice, and others were affected in only one genotype or exhibited significant genotype × treatment interactions. Functional differences between visceral fat of GHRKO and normal mice were confirmed by measurements of adipokine secretion, lipolysis, and expression of genes related to fat metabolism. We conclude that in the absence of GH signaling, the secretory activity of visceral fat is profoundly altered and unexpectedly promotes enhanced insulin sensitivity. The apparent beneficial effects of visceral fat in GHRKO mice may also explain why reducing adiposity by calorie restriction fails to improve insulin signaling or further extend longevity in these animals.
authors: College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA. michal.masternak@ucf.edu
authors: Michal M
authors: MM
authors: Masternak
authors: Andrzej
authors: A
authors: Bartke
authors: Feiya
authors: F
authors: Wang
authors: Adam
authors: A
authors: Spong
authors: Adam
authors: A
authors: Gesing
authors: Yimin
authors: Y
authors: Fang
authors: Adam B
authors: AB
authors: Salmon
authors: Larry F
authors: LF
authors: Hughes
authors: Teresa
authors: T
authors: Liberati
authors: Ravneet
authors: R
authors: Boparai
authors: John J
authors: JJ
authors: Kopchick
authors: Reyhan
authors: R
authors: Westbrook
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001831:Body Temperature; D031204:Caloric Restriction; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000601:surgery; D050356:Lipid Metabolism / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011986:Receptors, Somatotropin / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D007328:Insulin; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D005947:Glucose