A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss.

ABSTRACT: The emergence of glucagon-like peptide-1 agonists represents a notable advancement in the pharmacological treatment of obesity, yet complementary approaches are essential. Through phenotypic drug discovery, we developed promising nitroalkene-containing small molecules for obesity-related metabolic dysfunctions. Here, we present SANA, a nitroalkene derivative of salicylate, demonstrating notable efficacy in preclinical models of diet-induced obesity. SANA reduces liver steatosis and insulin resistance by enhancing mitochondrial respiration and increasing creatine-dependent energy expenditure in adipose tissue, functioning effectively in thermoneutral conditions and independently of uncoupling protein 1 and AMPK activity. Finally, we conducted a randomized, double-blind, placebo-controlled p

SUBMITTER: Cal K 

PROVIDER: S-EPMC12373507 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature