title: Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
abstract: To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.
authors.affiliation: Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel; Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Irit
authors.initials: I
authors.lastname: Hochberg
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Tran
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, United States of America.
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Barkan
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States of America; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Saltiel
authors.affiliation: Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, United States of America.
authors.forename: William F
authors.initials: WF
authors.lastname: Chandler
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States of America; Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, United States of America; Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Dave
authors.initials: D
authors.lastname: Bridges
mesh_terms: D000172:Acromegaly / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D000090943:Delta-5 Fatty Acid Desaturase; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics*; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D001786:Blood Glucose; D000090943:Delta-5 Fatty Acid Desaturase; C515497:IGFBP3 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; C000716847:FADS1 protein, human