Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice.
Conjugated linoleic acid (CLA) induces insulin resistance preceded by rapid depletion of the adipokines leptin and adiponectin, increased inflammation, and hepatic steatosis in mice. To determine the role of leptin in CLA-mediated insulin resistance and hepatic steatosis, recombinant leptin was coadministered with dietary CLA in ob/ob mice to control leptin levels and to, in effect, negate the leptin depletion effect of CLA. In a 2 x 2 factorial design, 6 week old male ob/ob mice were fed either a control diet or a diet supplemented with CLA and received daily intraperitoneal injections of either leptin or vehicle for 4 weeks. In the absence of leptin, CLA significantly depleted adiponectin and induced insulin resistance, but it did not increase hepatic triglyceride concentrations or adipose inflammation, marked by interleukin-6 and tumor necrosis factor-alpha mRNA expression. Insulin resistance, however, was accompanied by increased macrophage infiltration (F4/80 mRNA) in adipose tissue. In the presence of leptin, CLA depleted adiponectin but did not induce insulin resistance or macrophage infiltration. Despite this, CLA induced hepatic steatosis. In summary, CLA worsened insulin resistance without evidence of inflammation or hepatic steatosis in mice after 4 weeks. In the presence of leptin, CLA failed to worsen insulin resistance but induced hepatic steatosis in ob/ob mice.
Wendel
Angela A
AA
Department of Human Nutrition, Ohio State University, Columbus, OH 43210, USA.
Purushotham
Aparna
A
Liu
Li-Fen
LF
Belury
Martha A
MA
D052242:Adiponectin / Q000097:blood*; D000818:Animals; D001835:Body Weight; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism; D005947:Glucose / Q000032:analysis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage*; D050356:Lipid Metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D052242:Adiponectin; D004042:Dietary Fats, Unsaturated; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D044243:Linoleic Acids, Conjugated; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose