title: Female mice lacking p47phox have altered adipose tissue gene expression and are protected against high fat-induced obesity.
abstract: The current study was designed to determine if the NADPH-oxidase NOX2 plays a role in development of obesity after high fat feeding. Wild-type (WT) mice and mice lacking the essential cytosolic NOX2 system component p47(phox) (P47KO mice) were fed AIN-93G diets or high-fat diets (HFD) containing 45% fat and 0.5% cholesterol for 13 wk from weaning. Fat mass was increased to a similar degree by HFD in males of both genotypes (P < 0.05). However, female P47KO-HFD mice had no increase in adiposity or adipocyte size relative to female WT-HFD mice. Resistance to HFD-driven obesity in P47KO females was associated with increased expression of hepatic TFAM and UCP-2 mRNA, markers of mitochondrial number and uncoupling, and increased expression of hepatic mitochondrial respiratory complexes and whole body energy expenditure in response to HFD. Microarray analysis revealed significantly lower expression of mRNA encoding genes linked to energy metabolism, adipocyte differentiation (PPARγ), and fatty acid uptake (CD36, lipoprotein lipase), in fat pads from female P47KO-HFD mice compared with WT-HFD females. Moreover, differentiation of preadipocytes ex vivo was suppressed more by 17β-estradiol in cells from P47KO compared with cells from WT females in conjunction with overexpression of mRNA for Pref-1 (P < 0.05). HFD mice of both sexes were resistant to the development of hyperglycemia and hepatic steatosis (P < 0.05) and had reduced serum triglycerides, leptin, and adiponectin relative to WT-HFD mice (P < 0.05). These data suggest that NOX2 is an important regulator of metabolic homeostasis and diet-induced obesity.
authors.affiliation: Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, USA. RonisMartinJ@uams.edu
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Neha
authors.initials: N
authors.lastname: Sharma
authors.forename: Jamie
authors.initials: J
authors.lastname: Vantrease
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Borengasser
authors.forename: Matthew
authors.initials: M
authors.lastname: Ferguson
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mercer
authors.forename: Mario A
authors.initials: MA
authors.lastname: Cleves
authors.forename: Horacio
authors.initials: H
authors.lastname: Gomez-Acevedo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D002469:Cell Separation; D059305:Diet, High-Fat / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D048788:Growth and Development / Q000187:drug effects / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000172:deficiency* / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D012727:Sex Characteristics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D004958:Estradiol; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D013755:Tetradecanoylphorbol Acetate
keywords: NADPH-oxidase; adipose; metabolism; obesity; p47phox