Endocrine Abstracts

High level of triglycerides (TG) in plasma is a risk factor for cardiovascular disease. Various treatment strategies aimed at decreasing plasma TG concentrations affect synthesis of lipoproteins in the liver and/or increase clearance of TG by peripheral tissues. Lipid-lowering effects of fibrates reflects modulation of the liver metabolism. Antidiabetic agents thiazolidinediones (TZD) lower plasma TG by enhancing lipoprotein lipase activity in white adipose tissue (WAT). Long-chain polyunsaturated fatty acids of n-3 series, namely eicosapentaenoic (EPA; 20:5 n-3) and docosahexaenoic (DHA; 22:6 n-3) acids, that are abundant in sea fish, act as hypolipidemics, while decreasing the production of lipoproteins. EPA and DHA may also affect the TG clearance. Most of the above mentioned treatments induce expression of mitochondrial uncoupling proteins (UCPs) in WAT. The aims of our studies were to characterize: (i) the potency of WAT to decrease plasma TG levels; and (ii) the involvement of WAT in the hypolipidemic effects of EPA and DHA. A large potency of WAT to decrease plasma TG was demonstrated using transgenic mice with ectopic expression of UCP1 in WAT (aP2-Ucp1 mice). The ectopic UCP1 induces respiratory uncoupling in WAT, hence stimulating in situ lipid oxidation and mitochondrial biogenesis, and clearance of plasma TG. Moreover, aP2-Ucp1 mice were resistant to high-fat diet induced obesity and showed higher whole body lipid oxidation. The obesity in wild type mice was also prevented by replacing only 9% of the dietary lipids by EPA and DHA. This dietary treatment lowered plasma TG, while inducing lipid oxidation and mitochondrial biogenesis in WAT. These results supported a possibility to induce a metabolic switch in WAT, which may change whole body phenotype, including the lowering of plasma TG. Further studies are required to assess the importance of this switch for the effectiveness of the lipid-lowering treatments.