title: Novel genes of visceral adiposity: identification of mouse and human mesenteric estrogen-dependent adipose (MEDA)-4 gene and its adipogenic function.
abstract: Visceral adiposity represents a high risk factor for type 2 diabetes, metabolic syndrome, and cardiovascular disease as well as various cancers. While studying sex hormone imbalance-induced early obesity and late onset of insulin resistance in FSH receptor knock out female mice, we identified a novel mesenteric estrogen-dependent adipose gene (MEDA-4) selectively up-regulated in a depot-specific manner in mesenteric adipose tissue. Meda-4 cloned from both mouse and human adipose tissue codes for a 34-kDa cytosolic protein with 91% homology. Mouse Meda-4 mRNA is expressed highest in visceral adipose tissue and localizes predominantly in the adipocyte fraction. Human MEDA-4 is also more abundant in omental fat than sc depot in obese patients. In 3T3-L1 cells endogenous Meda-4 expression increases early during differentiation, and its overexpression promotes differentiation of preadipocytes into adipocytes and enhances glucose uptake. Conversely, short hairpin RNA-mediated knockdown of Meda-4 reduces both adipogenic and glucose uptake potential. In promoting adipogenesis, Meda-4 up-regulates transcription factor peroxisome proliferator-activated receptor-γ2. Meda-4 promotes lipid accumulation in adipocytes, regulating adipocyte fatty acid-binding protein 2, CD36, lipoprotein lipase, hormone-sensitive lipase, acyl-Coenzyme A oxidase-1, perilipin-1, and fatty acid synthase expression. 17β-Estradiol reduced Meda-4 expression in mesenteric adipose tissue of ovariectomized mice and in 3T3-L1 adipocytes. Thus our study identifies Meda-4 as a novel adipogenic gene, capable of promoting differentiation of preadipocytes into adipocytes, increasing lipid content and glucose uptake in adipocytes. Therefore it might play an important role in adipose tissue expansion in normal and aberrant hormonal conditions and pathophysiological states.
authors.affiliation: Molecular Endocrinology Laboratory, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada H2W 1R7.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: M R
authors.initials: MR
authors.lastname: Sairam
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D050154:Adiposity / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D003001:Cloning, Molecular; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D059467:Transcriptome
chemical_list: C574228:MEDA-4 protein, mouse; D036361:Peptide Hormones