Trace Elements, PPARs, and Metabolic Syndrome

Abstract

Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.

Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma

“…However, in primary biliary cirrhosis, the supplementation of selenium did not show any antioxidant activities, while the renal excretion was increased, suggesting that a cirrhotic liver could not take advantage of selenium adequately [121]. Although selenium administration helps in the recovery of hepatic steatosis via PPAR-α activation in some diabetic mouse models [122], selenium supplementation to humans has been cautioned to increase the risk of type 2 diabetes [123]. It therefore remains difficult to draw any definite conclusions about selenium supplementation as an antioxidant.…”

Bioinformatics Analyses Reveal the Prognostic Value and Biological Roles of SEPHS2 in Various Cancers

“…Recent studies have reported that selenoproteins modify the mode of action of PPAR-γ. 56 , 57 Se deficiency inhibits PPAR-γ activity, promotes nuclear factor-κB (NF-κB) activation in tumor cells, and increases tumor invasiveness and immunosuppression. 58 As mentioned earlier, SEPHS2 is a selenoprotein that is required for the synthesis of selenoproteins.…”

Effects of Lactobacillus fermentum CQPC04 on Lipid Reduction in C57BL/6J Mice

“…PPAR-γ is a nuclear receptor protein that induces adipocyte differentiation by stimulating the expression of several genes involved in preadipocyte proliferation. Activated PPAR-γ terminates the cell differentiation cycle and stimulates the expression of adipocyte-specific genes, resulting in increased cellular energy uptake (Shi et al, 2020). CPT1 is a rate-limiting enzyme in the beta oxidation process of fatty acids.…”