title: Pmch-deficiency in rats is associated with normal adipocyte differentiation and lower sympathetic adipose drive.
abstract: The orexigenic neuropeptide melanin-concentrating hormone (MCH), a product of Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch is expressed in hypothalamic neurons that ultimately are components in the sympathetic nervous system (SNS) drive to white and interscapular brown adipose tissue (WAT, iBAT, respectively). MCH binds to MCH receptor 1 (MCH1R), which is present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal WAT mass and adipocyte morphology (size and number) throughout development, and indices of sympathetic activation in WAT and iBAT during adulthood. Moreover, using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1 adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and perirenal WAT mass by reducing adipocyte size, but not number. In line with this, in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic adipose drive) in WAT and iBAT than wild-type rats. Collectively, our data indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation, whereas Pmch-deficiency in laboratory rats lowers adiposity throughout development and sympathetic adipose drive during adulthood.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joram D
authors.initials: JD
authors.lastname: Mul
authors.forename: Eoghan
authors.initials: E
authors.lastname: O'Duibhir
authors.forename: Yogendra B
authors.initials: YB
authors.lastname: Shrestha
authors.forename: Arjen
authors.initials: A
authors.lastname: Koppen
authors.forename: Peter
authors.initials: P
authors.lastname: Vargoviç
authors.forename: Pim W
authors.initials: PW
authors.lastname: Toonen
authors.forename: Eleen
authors.initials: E
authors.lastname: Zarebidaki
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnansky
authors.forename: Eric
authors.initials: E
authors.lastname: Kalkhoven
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bartness
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000172:deficiency* / Q000235:genetics; D008543:Melanins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D010907:Pituitary Hormones / Q000172:deficiency* / Q000235:genetics; D051381:Rats; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
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