title: Regulators of mitochondrial quality control differ in subcutaneous fat of metabolically healthy and unhealthy obese monkeys.
abstract: Obesity exists with and without accompanying cardiometabolic disease, termed metabolically unhealthy obesity (MUO) and healthy obesity (MHO), respectively. Underlying differences in the ability of subcutaneous (SQ) fat to respond to nutrient excess are emerging as a key pathway. This study aimed to document the first spontaneous animal model of MHO and MUO and differences in SQ adipose tissue.
  
  
  
  Vervet monkeys (Chlorocebus aethiops; N = 171) were screened for metabolic syndrome. A subset of MHO and MUO monkeys (n = 6/group) had SQ fat biopsies collected for histological evaluations and examination of key mitochondrial proteins.
  
  
  
  Obesity was seen in 20% of monkeys, and within this population, 31% were healthy, which mirrors human prevalence estimates. MUO monkeys had more than 60% lower adiponectin concentrations despite similar fat cell size, uncoupling protein 3, and activated macrophage abundance. However, alternatively activated/anti-inflammatory macrophages were 70% lower. Deficiencies of 50% or more in mitochondrial quality control regulators and selected mitochondrial fission and fusion markers were observed in the SQ fat of MUO monkeys despite comparable mitochondrial content.
  
  
  
  A novel and translatable spontaneously obese animal model of MHO and MUO, occurring independently of dietary factors, was characterized. Differences in mitochondrial quality and inflammatory cell populations of subcutaneous fat may underpin divergent metabolic health.
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
authors.forename: Kylie
authors.initials: K
authors.lastname: Kavanagh
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Davis
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Peters
authors.affiliation: Animal Resources Program, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
authors.forename: Andre C
authors.initials: AC
authors.lastname: LeGrand
authors.affiliation: Sticht Center on Aging and Department of Internal Medicine, Section on Gerontology and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Manish S
authors.initials: MS
authors.lastname: Bharadwaj
authors.affiliation: Sticht Center on Aging and Department of Internal Medicine, Section on Gerontology and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Anthony J A
authors.initials: AJ
authors.lastname: Molina
mesh_terms: D052242:Adiponectin / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism*; D000071247:Uncoupling Protein 3 / Q000032:analysis
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D000071247:Uncoupling Protein 3