Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic Agents

Figure 3

(A) During obesity, the adipocytes will have reduced lipid storage capacity, leading to increased lipolysis and release of free fatty acids (FFAs), inflammatory agents, and disturbed adipokine release. The FFAs will be repackaged to triglycerides (TGs) in the liver where they are released as very low-density lipoprotein particles (VLDL). Together this has secondary effects on organs such as skeletal muscle and pancreas, as well as liver, and can result in hyperlipidemia, tissue lipid deposition, mitochondrial malfunction, insulin resistance, increased insulin production, and pancreatic β-cell disruption. (B) The effect of tetradecylthioacetic acid-(TTA-) treatment on metabolic syndrome. In the liver, TTA treatment will increase the degradation of FFA, by the induction of both mitochondrial and peroxisomal genes involved in β-oxidation. The excess FFA released from adipose tissue during metabolic syndrome (hyperlipidemia) is drained from the blood, thereby reducing TG, cholesterol, and FFA levels. In addition the TTA-induced increase in uncoupling protein 3 (UCP3) could increase energy expenditure, as well as function as a protection from the excess ROS production observed with obesity and high levels of FA degradation. The effect of TTA on liver is probably due to PPARα-mediated mechanisms, while the effect on adipose tissue may arrive from PPARγ as well as PPARα activation. In adipose tissue, the main effect of TTA is an increase in the brown adipose tissue marker Ucp1 in visceral adipose tissue (VAT) indicating higher energy expenditure and heat production. The higher metabolic activity of VAT compared to SAT will cause it to be the major source of FFA during increased hepatic β-oxidation. Together, this may explain the specific reduction of these risk-linked adipose depots with TTA-treatment.