title: Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure.
abstract: OBJECTIVE
  Recent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis.
  
  
  METHODS
  We investigated the in vitro role of AHNAK in adipogenesis using adipose-derived mesenchymal stem cells (ADSCs) and C3H10T1/2 cells. AHNAK-KO male mice were fed a high-fat diet (HFD; 60% calories from fat) and examined for glucose and insulin tolerances, for body fat compositions, and by hyperinsulinemic-euglycemic clamping. Energy expenditures were assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in white or brown adipose tissues.
  
  
  RESULTS
  Adipogenesis in ADSCs was impaired in AHNAK-KO mice. The loss of AHNAK led to decreased BMP4/SMAD1 signaling, resulting in the downregulation of key regulators of adipocyte differentiation (P<0.05). AHNAK directly interacted with SMAD1 on the Pparγ2 promoter. Concomitantly, HFD-fed AHNAK-KO mice displayed reduced hepatosteatosis and improved metabolic profiles, including improved glucose tolerance (P<0.001), enhanced insulin sensitivity (P<0.001), and increased energy expenditure (P<0.05), without undergoing alterations in food intake and physical activity.
  
  
  CONCLUSIONS
  AHNAK plays a crucial role in body fat accumulation by regulating adipose tissue development via interaction with the SMAD1 protein and can be involved in metabolic homeostasis.
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Il Yong
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Yo Na
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Ewha Womans University, Seoul, South Korea.
authors.forename: Sun Mee
authors.initials: SM
authors.lastname: Shin
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute and Division of Endocrinology Gil Medical Center, Gachon University of Medicine and Science, Incheon, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Roh
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Life Sciences, Ewha Womans University, Seoul, South Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Ewha Research Center for Systems Biology, Ewha Womans University, Seoul, South Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Institute of Medical Engineering, Yonsei University, Wonju, South Korea.
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Ko
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute and Division of Endocrinology Gil Medical Center, Gachon University of Medicine and Science, Incheon, South Korea.
authors.forename: Cheol Soo
authors.initials: CS
authors.lastname: Choi
authors.affiliation: Division of Life Sciences, Ewha Womans University, Seoul, South Korea.
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; Korea Mouse Phenotyping Center (KMPC), Seoul National University, Seoul, South Korea; Interdisciplinary Program for Bioinformatics, Program for Cancer Biology and BIO-MAX Institute, Seoul National University, Seoul, South Korea.
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D002454:Cell Differentiation; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D051898:Smad1 Protein / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology
chemical_list: C489572:Ahnak protein, mouse; D007328:Insulin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D005947:Glucose