Incorporation of conjugated linoleic acid into brain lipids is not necessary for conjugated linoleic acid-induced reductions in feed intake or body fat in mice.

Dietary conjugated linoleic acid (CLA) causes reduced feed intake (FI) and body fat (BF). It is unknown, though, if CLA incorporation into tissues, alterations in serum hormones, and/or appetite-regulating neuropeptides are involved. We hypothesized that CLA incorporation into brain lipids would be correlated with changes in appetite-regulating neuropeptide expression and reductions in FI and BF. Male mice (n = 150; 9 weeks old, ICR) received the control diet ad libitum (CON), 2% CLA diet ad libitum (CLA), or control diet pair-fed to the intake of CLA-fed mice for 1, 2, 3, 5, or 7 days. Both FI and body weight were measured daily, and a BF index was calculated. Liver, adipose, and brain fatty acids; serum insulin, leptin, and peptide YY; and arcuate nucleus neuropeptide Y, agouti-related protein, and α-melanocyte-stimulating hormone protein were determined. Mice fed CLA ate less (P < .05) than did the CON on days 1, 2, 3, and 7 but were leaner (P < .05) only on day 7. Mice that received the control diet pair-fed to the intake of CLA-fed mice did not differ in BF from the CON. By days 1 and 2, CLA isomers were incorporated into the liver and adipose but not in the brain. Insulin was increased in CLA-fed mice on days 5 and 7, and leptin was decreased on day 7. Peptide YY and the neuropeptides did not differ. Tissue CLA was not correlated with FI, body weight, or BF but was positively correlated with insulin and negatively correlated with leptin. The reduction in FI is not sufficient to cause the reduction in BF, and tissue CLA accumulation does not appear to be required.

Conjugated linoleic acid-induced fat loss dependence on Delta6-desaturase or cyclooxygenase.

OBJECTIVE: To determine whether conjugated linoleic acid (CLA)-induced body fat loss is dependent upon metabolism of CLA by Delta6-desaturase, cyclooxygenase, or lipoxygenase. METHODS AND PROCEDURES: Mice were fed diets with or without CLA and inhibitors to either Delta6-desaturase (SC-26196), cyclooxygenase (aspirin), or lipoxygenase (nordihydroguaiaretic acid (NDGA)) for 2 weeks. Body fat percent, lean mass, fat pad weights, liver weight, and fatty acid concentrations were determined. A Delta6-desaturase index was calculated, and adipose tissue prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) concentrations were determined to confirm enzyme inhibition. RESULTS: Inhibition of Delta6-desaturase and cyclooxygenase were confirmed. CLA caused a loss of body fat (P < 0.001). The body fat loss was blocked (P = 0.08) by the Delta6-desaturase inhibitor at a dose that decreased (P < 0.05) the calculated index. Aspirin and NDGA had no effect on body fat and did not interact with CLA. DISCUSSION: Inhibition of Delta6-desaturase prevented CLA from being able to cause a body fat loss. Therefore, a desaturated metabolite of CLA appears to be involved in the CLA antiobesity effect. This effect of CLA does not seem dependent upon cyclooxygenase. Because lipoxygenase activity was not blocked by NDGA, we cannot draw conclusions about its importance in mediating the antiobesity effect of CLA.