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

Int J Mol Sci. 2015 Dec 24;17(1):20. doi: 10.3390/ijms17010020.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / therapeutic use
  • Dietary Carbohydrates / adverse effects*
  • Female
  • Fructose / adverse effects
  • Gene Expression Regulation
  • Humans
  • Hypertension / etiology
  • Hypertension / genetics*
  • Hypertension / pathology
  • Hypertension / prevention & control
  • Kidney / metabolism
  • Kidney / pathology
  • Maternal Exposure
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / pathology
  • Metabolic Syndrome / prevention & control
  • Nutritional Status
  • Peroxisome Proliferator-Activated Receptors / antagonists & inhibitors
  • Peroxisome Proliferator-Activated Receptors / genetics*
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / pathology
  • Prenatal Exposure Delayed Effects / prevention & control
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction

Substances

  • Antihypertensive Agents
  • Dietary Carbohydrates
  • Peroxisome Proliferator-Activated Receptors
  • Protein Isoforms
  • Fructose