title: Reducing the dietary omega-6:omega-3 utilizing α-linolenic acid; not a sufficient therapy for attenuating high-fat-diet-induced obesity development nor related detrimental metabolic and adipose tissue inflammatory outcomes.
abstract: OBJECTIVE
  To examine the effect of manipulating the omega-6:omega-3 (1∶1, 5∶1, 10∶1, and 20∶1) utilizing only α-linolenic and linoleic acid within a clinically-relevant high-fat diet (HFD) composed of up to seven sources of fat and designed to be similar to the standard American diet (MUFA∶PUFA of 2∶1, 12% and 40% of calories from saturated and total fat, respectively) on body composition, macrophage polarization, inflammation, and metabolic dysfunction in mice.
  
  
  METHODS
  Diets were administered for 20 weeks. Body composition and metabolism (HOMA index and lipid profile) were examined monthly. GC-MS was utilized to determine the eicosapentaenoic acid (EPA):arachidonic acid (AA) and the docosahexaenoic acid (DHA):AA in AT phospholipids. Adipose tissue (AT) mRNA expression of chemokines (MCP-1, Fetuin-A, CXCL14), marker genes for M1 and M2 macrophages (CD11c and CD206, respectively) and inflammatory markers (TNF-α, IL-6, IL-1β, TLR-2, TLR-4, IL-10, GPR120) were measured along with activation of NFκB, JNK, and STAT-3. Macrophage infiltration into AT was examined using F4/80 immunohistochemistry.
  
  
  RESULTS
  Any therapeutic benefit produced by reducing the omega-6:omega-3 was evident only when comparing the 1∶1 to 20∶1 HFD; the 1∶1 HFD resulted in a lower TC:HDL-C and decreased AT CXCL14 gene expression and AT macrophage infiltration, which was linked to a higher EPA:AA and DHA:AA in AT phospholipids. However, despite these effects, and independent of the omega-6:omega-3, all HFDs, in general, led to similar levels of adiposity, insulin resistance, and AT inflammation.
  
  
  CONCLUSIONS
  Reducing the omega-6:omega-3 using α-linolenic acid is not an effective therapy for attenuating obesity and type II diabetes mellitus development.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Kandy T
authors.initials: KT
authors.lastname: Velázquez
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: McClellan
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Cranford
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walla
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D050154:Adiposity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat; D005215:Fasting / Q000097:blood / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010743:Phospholipids / Q000378:metabolism; D016896:Treatment Outcome; D017962:alpha-Linolenic Acid / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D043371:Fatty Acids, Omega-6; D008055:Lipids; D010743:Phospholipids; D017962:alpha-Linolenic Acid
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