title: Activation of classical brown adipocytes in the adult human perirenal depot is highly correlated with PRDM16-EHMT1 complex expression.
abstract: Brown fat generates heat to protect against cold and obesity. Adrenergic stimulation activates the thermogenic program of brown adipocytes. Although the bioactivity of brown adipose tissue in adult humans had been assumed to very low, several studies using positron emission tomography-computed tomography (PET-CT) have detected bioactive brown adipose tissue in adult humans under cold exposure. In this study, we collected adipose tissues obtained from the perirenal regions of adult patients with pheochromocytoma (PHEO) or non-functioning adrenal tumors (NF). We demonstrated that perirenal brown adipocytes were activated in adult patients with PHEO. These cells had the molecular characteristics of classical brown fat rather than those of beige/brite fat. Expression of brown adipose tissue markers such as uncoupling protein 1 (UCP1) and cell death-inducing DFFA-like effector A (CIDEA) was highly correlated with the amounts of PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16) - euchromatic histone-lysine N-methyltransferase 1 (EHMT1) complex, the key transcriptional switch for brown fat development. These results provide novel insights into the reconstruction of human brown adipocytes and their therapeutic application against obesity and its complications such as type 2 diabetes.
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Gaku
authors: G
authors: Nagano
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Haruya
authors: H
authors: Ohno
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Kenji
authors: K
authors: Oki
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Kazuhiro
authors: K
authors: Kobuke
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Tsuguka
authors: T
authors: Shiwa
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Masayasu
authors: M
authors: Yoneda
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors: Nobuoki
authors: N
authors: Kohno
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors; C455847:EHMT1 protein, human; D011495:Histone-Lysine N-Methyltransferase