PPARs Link Early Life Nutritional Insults to Later Programmed Hypertension and Metabolic Syndrome

Abstract

Hypertension is an important component of metabolic syndrome. Adulthood hypertension and metabolic syndrome can be programmed in response to nutritional insults in early life. Peroxisome proliferator-activated receptors (PPARs) serve as a nutrient-sensing signaling linking nutritional programming to hypertension and metabolic syndrome. All three members of PPARs, PPARα, PPARβ/δ, and PPARγ, are expressed in the kidney and involved in blood pressure control. This review provides an overview of potential clinical applications of targeting on the PPARs in the kidney to prevent programmed hypertension and metabolic syndrome, with an emphasis on the following areas: mechanistic insights to interpret programmed hypertension; the link between the PPARs, nutritional insults, and programmed hypertension and metabolic syndrome; the impact of PPAR signaling pathway in a maternal high-fructose model; and current experimental studies on early intervention by PPAR modulators to prevent programmed hypertension and metabolic syndrome. Animal studies employing a reprogramming strategy via targeting PPARs to prevent hypertension have demonstrated interesting results. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies, to halt the globally-growing epidemic of metabolic syndrome-related diseases.

Keywords: developmental programming; hypertension; kidney; metabolic syndrome; nutrient sensing; peroxisome proliferator-activated receptor.

Figure 1

A schema showing the link between maternal nutritional insults and programmed hypertension via PPAR signaling pathway. P, phosphorylation; Ac, acetylation.

Figure 2

Gene members (green rectangle) in the PPAR signaling pathway that are regulated by maternal high fructose in the male offspring kidney at one day of age (red stars). Data were analyzed using the KEGG pathway feature of the DAVID software [45]. Solid line, downstream signal and PPAR target genes; Dotted line, PPARs regulated mechanisms.