title: Hypothalamic regulation of adiposity: the role of 11beta-hydroxysteroid dehydrogenase type 1.
abstract: Following extensive suprasellar operations for excision of hypothalamic tumors, some patients develop morbid obesity despite receiving replacement doses of glucocorticoids. Urine analysis of cortisol and cortisone metabolites show that 11-OH/11-oxo ratios are significantly higher in patients with hypothalamic obesity, indicating enhanced 11beta-HSD1 activity. This correlates with the visceral-to-subcutaneous fat ratio. The consequence of increased 11beta-HSD1 activity and a shift of the steroid inter-conversion towards cortisol may contribute to the effects of the latter in adipose tissue. The message from the hypothalamus to adipocyte 11beta-HSD-1 involves hormones, the sympathetic nervous system and cytokines. CRH and ACTH downregulate 11beta-HSD-1 activity and induce lipolysis. Tumor necrosis factor-alpha and interleukin-1beta upregulate 11beta-HSD-1 expression and activity, while enhancing lipolysis. The sympathetic nervous system exerts its effects through beta-adrenergic upregulation and alpha-adrenergic downregulation of 11beta-HSD-1 activity. Inhibition of 11beta-HSD-1 suppresses preadipocyte differentiation into mature adipocytes, and may provide a therapeutic tool.
authors.affiliation: Division of Endocrinology, Meyer Children's Hospital, PO Box 9602, Rambam Medical Center, Haifa 31096, Israel. z_hochberg@rambam.health.gov.il
authors.forename: Z
authors.initials: Z
authors.lastname: Hochberg
authors.forename: M
authors.initials: M
authors.lastname: Friedberg
authors.forename: L
authors.initials: L
authors.lastname: Yaniv
authors.forename: T
authors.initials: T
authors.lastname: Bader
authors.forename: D
authors.initials: D
authors.lastname: Tiosano
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000031:analogs & derivatives* / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D003348:Cortisone / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007031:Hypothalamus / Q000503:physiopathology*; D007375:Interleukin-1 / Q000502:physiology; D053583:Interleukin-1beta; D008066:Lipolysis / Q000502:physiology; D009765:Obesity / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D003348:Cortisone; D006854:Hydrocortisone