Treatment With Dietary trans10cis12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With the Metabolic Syndrome

Abstract

OBJECTIVE -Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome.RESEARCH DESIGN AND METHODS -In a randomized, double-blind controlled trial, abdominally obese men (n ϭ 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment.RESULTS -Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P Ͻ 0.01) and glycemia (4%; P Ͻ 0.001) and reduced HDL cholesterol (Ϫ4%; P Ͻ 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (Ϫ2%; P Ͻ 0.05).CONCLUSIONS -These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.

Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity

“…Of the 60 men, 57 completed the intervention. Reasons for dropping out have been reported elsewhere [6]. Insulin sensitivity decreased and fasting glucose increased, but insulin concentrations did not significantly change after t10c12CLA when compared with control subjects (Table 2) [6].…”

“…This study is a re-analysis of a controlled study. As previously described [6], non-diabetic, obese Swedish men were included (Table 1). Subjects on antidiabetic and/or lipidlowering drugs or with diagnosed metabolic diseases were excluded.…”

“…Insulin sensitivity, intact proinsulin, specific insulin, glucose, C-peptide and plasma adiponectin concentrations were determined before and after the intervention. The data on insulin sensitivity and the protocol have been described [6]. A total of 60 men were randomly assigned (double-blind) to a 3-month-long supplementation of 3.4 g of purified t10c12CLA, 3.4 g CLA-isomer mixture or 3.4 g olive oil (control).…”

“…Insulin sensitivity was determined by euglycaemic-hyperinsulinaemic clamp as previously described [6]. Insulin sensitivity (M) was the glucose infusion rate (mg·kg bw −1 ·min −1 ).…”

“…We recently reported that trans10cis12 (t10c12)-conjugated linoleic acid (CLA) causes isomer-specific insulin resistance in obese men [6]. The insulin resis-tance thus induced by t10c12CLA gave us a unique possibility to study the longitudinal relationships between insulin resistance and changes in insulin-like peptides.…”