Heavy metal-induced lipogenic gene aberration, lipid dysregulation and obesogenic effect: a review

Abstract

Lipids are high energy, complex biomolecular compounds essential for cellular and organellar membrane formation. Accumulation of circulatory lipids is however associated with pathophysiological conditions including cardiometabolic disorders, diabetic dyslipidemia and obesity. Epidemiological studies have correlated heavy-metal exposure with dyslipidemias and metabolic syndrome. Here, we review the role of cadmium, lead, mercury and arsenic on inducing dyslipidemias through lipid metabolism dysregulation, with focus on metal effects on lipogenic genes, gut microbiome and endocrine secretion. The main gene transcription factors impaired by heavy metals are CCAAT-enhancer binding protein, peroxisome proliferative-activated receptor, sterol regulatory element binding protein, carbohydrate responsive element binding protein and liver × receptor. These factors regulate genes responsible for β-oxidation, de novo lipogenesis, and the synthesis and transport of fatty acids, cholesterol, phospholipids and triglycerides. Dysregulated lipid profiles in organisms exposed to metals show higher cholesterol and triglycerides, very low-density lipoprotein and non-high density lipoprotein cholesterol levels, with a corresponding low high-density lipoprotein cholesterol. Hormones and gut microbiome are also impaired by heavy-metal exposure.