title: Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways.
abstract: Menopause is associated with increased adiposity and greater risk of metabolic disease. In the ovariectomized (OVX) rodent model of menopause, increased adiposity is prevented by estrogen (E2) replacement, reflecting both anorexigenic and potentially metabolic actions of E2. To elucidate metabolic and molecular mechanisms by which E2 regulates fat storage and fat mobilization independently of reduced energy intake, C57 BL/6 mice were ovariectomized, randomized to estrogen (OVX-E2) or control pellet implants (OVX-C), and pairfed for 40 days. E2 treatment was associated with reduced adipose mass and adipocyte size and down-regulation of lipogenic genes in adipocytes under the control of sterol-regulatory element-binding protein 1c. Adipocytes of OVX-E2 mice contained >3-fold more perilipin protein than adipocytes of pairfed control (OVX) mice, and this difference was associated with enhanced ex vivo lipolytic response to catecholamines and with greater levels of serum-free fatty acids following fasting. As in adipose tissue, E2 decreased the expression of lipogenic genes in liver and skeletal muscle. In the latter, E2 appears to promote the partitioning of free fatty acids toward oxidation and away from triglyceride storage by up-regulating the expression of peroxisome proliferation activator receptor-delta and its downstream targets and also by directly and rapidly activating AMP-activated protein kinase. Thus, novel genomic and non-genomic actions of E2 promote leanness in OVX mice independently of reduced energy intake.
authors.affiliation: Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: D'Eon
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Souza
authors.forename: Mark
authors.initials: M
authors.lastname: Aronovitz
authors.forename: Martin S
authors.initials: MS
authors.lastname: Obin
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fried
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
mesh_terms: D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D002352:Carrier Proteins; D002395:Catecholamines / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D016678:Genome; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000378:metabolism; D008055:Lipids; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D002352:Carrier Proteins; D002395:Catecholamines; D016895:Culture Media, Serum-Free; D004967:Estrogens; D007328:Insulin; D020738:Leptin; D008055:Lipids; D009097:Multienzyme Complexes; D047494:PPAR delta; D000070778:Perilipin-1; D010750:Phosphoproteins; D052243:Resistin; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen