OBJECTIVE Peroxisome proliferator–activated receptor (PPAR)-α/γ dual agonists have been developed to alleviate metabolic disorders. However, several PPARα/γ dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARα/γ dual agonist, CG301269, on metabolic disorders both in vitro and in vivo. RESEARCH DESIGN AND METHODS Function of CG301269 as a PPARα/γ dual agonist was assessed in vitro by luciferase reporter assay, mammalian one-hybrid assay, and analyses of PPAR target genes. In vitro profiles on fatty acid oxidation and inflammatory responses were acquired by fatty acid oxidation assay and quantitative (q)RT-PCR of proinflammatory genes. In vivo effect of CG301269 was examined in db/db mice. Total body weight and various tissue weights were measured, and hepatic lipid profiles were analyzed. Systemic glucose and insulin tolerance were measured, and the in vivo effect of CG301269 on metabolic genes and proinflammatory genes was examined by qRT-PCR. RESULTS CG301269 selectively stimulated the transcriptional activities of PPARα and PPARγ. CG301269 enhanced fatty acid oxidation in vitro and ameliorated insulin resistance and hyperlipidemia in vivo. In db/db mice, CG301269 reduced inflammatory responses and fatty liver, without body weight gain. CONCLUSIONS We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders.

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Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex‐matched non‐IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD‐specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non‐IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.

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