title: Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice.
abstract: BACKGROUND
  Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance.
  
  
  OBJECTIVE
  We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism.
  
  
  METHODS
  Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured.
  
  
  RESULTS
  By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation.
  
  
  CONCLUSIONS
  These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss.
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Laura J
authors.identifier: http://orcid.org/0000-0002-6789-5916
authors.initials: LJ
authors.lastname: den Hartigh
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Shari
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Leela
authors.initials: L
authors.lastname: Goodspeed
authors.affiliation: Department of Medicine, Cardiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wietecha
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Houston
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omer
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Savitha
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: G A Nagana
authors.initials: GA
authors.lastname: Gowda
authors.affiliation: Department of Medicine, Cardiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.affiliation: Department of Oral Health Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.affiliation: Department of Medicine, Metabolism, University of Washington, Seattle, Washington, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
chemical_list: D044243:Linoleic Acids, Conjugated; D005947:Glucose