Question

Which of the following is a Proliferator-Activated Receptor-Alpha (PPAR-α) agonist?

• A. Sulfonylurea
• B. Metformin
• C. Acarbose
• D. Pioglitazone

Hint:

PPAR-α agonists mainly affect lipid metabolism (fibrates), PPAR-γ agonists improve insulin sensitivity (thiazolidinediones like pioglitazone).

Answer 1

The Correct Option is D

Proliferator-Activated Receptors (PPARs) are nuclear receptor proteins that function as transcription factors regulating the expression of genes. There are three subtypes: PPAR-$α$, PPAR-$γ$, and PPAR-$β/δ$, each with distinct roles in metabolism. - PPAR$α$ agonists mainly regulate lipid metabolism, increasing fatty acid oxidation, and are primarily targeted by fibrates (e.g., fenofibrate). - PPAR-$γ$ agonists regulate glucose metabolism and insulin sensitivity and are the targets of thiazolidinediones (TZDs) such as pioglitazone and rosiglitazone. - Although the question mentions PPAR-$α$, pioglitazone primarily acts as a PPAR-$γ$ agonist; however, pioglitazone also exhibits some affinity for PPAR-$α$, contributing to its beneficial effects on lipid metabolism besides glucose control. - Sulfonylureas stimulate insulin release from pancreatic $β$-cells. - Metformin acts by reducing hepatic glucose production and increasing insulin sensitivity but does not act via PPARs. - Acarbose is an alpha-glucosidase inhibitor delaying carbohydrate absorption in the intestine. Thus, among the given options, pioglitazone is the closest PPAR agonist, specifically PPAR-$γ$, but also with some PPAR $α$ activity, making it the correct answer.