Short-term cooling increases serum angiopoietin-like 4 levels in healthy lean men

Background: Cold exposure enhances sympathetic outflow to peripheral tissues, thereby stimulating intracellular lipolysis in white adipose tissue and increasing the lipoprotein lipase-dependent uptake and combustion of triglyceride-derived fatty acids (FAs) by brown adipose tissue. Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase and can be regulated by cold exposure, at least in mice.

Objective: In the present study, we examined the effect of short-term mild cooling on serum ANGPTL4 levels in healthy lean men of White Caucasian and South Asian descent.

Methods: Healthy, lean White Caucasian (n = 12) and South Asian (n = 12) men were exposed to an individualized cooling protocol for 2 hours. Serum ANGPTL4 levels were measured before and after cooling, and its relation with previously measured parameters (ie, free fatty acid [FFA] levels, body fat percentage, and resting energy expenditure) was determined.

Results: Short-term cooling increased ANGPTL4 levels (+17%, P < .001). Thermoneutral ANGPTL4 levels positively correlated with FFA levels (R² = 0.250, P < .05) and body fat percentage (R² = 0.338, P < .05). Furthermore, ANGPTL4 negatively correlated with resting energy expenditure (R² = 0.235, P < .05). The relative increase in ANGPTL4 levels was higher in White Caucasians compared with South Asians (25 ± 4 vs 9 ± 4%, P < .05).

Conclusion: Short-term cooling increases ANGPTL4 levels in healthy lean men. We anticipate that FFA liberated from white adipose tissue during cooling increases ANGPTL4 to limit uptake of triglyceride-derived FA by this tissue.