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- Skeletal muscle expression of adipose-specific phospholipase in peripheral artery diseasePublication . Parmer, Caitlin; De Sousa-Coelho, Ana Luísa; Cheng, Henry S.; Daher, Grace; Burkart, Alison; Dreyfuss, Jonathan M.; Pan, Hui; Prenner, Joshua C.; Keilson, Jessica M.; Pande, Reena; Henkin, Stanislav; Feinberg, Mark W.; Patti, Mary Elizabeth; Creager, Mark A.Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) wasPLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR;PLA2G16was downregulated by 68% in patients with PAD (p< 0.001). Expression ofPla2g16was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression ofPla2g16in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.
- Editorial: FGF21 as a therapeutic target for obesity and insulin resistance: from rodent models to humansPublication . De Sousa-Coelho, Ana Luísa; Rodriguez-Rodriguez, R.; Softic, S.; Jonker, J. W.; Relat, J.Obesity is a global pandemic that requires the urgent development of therapies and prevention strategies. To define new pharmacologic therapies or nutritional approaches it is mandatory to find new targets. Fibroblast growth factor 21 (FGF21) is considered a potential target to treat obesity, due to its favorable metabolic activity, signalling pathways and regulatory mechanisms. It is well-documented that FGF21 is induced by a wide range of biological stress conditions and a key signal that communicates and coordinates the physiologic response to restore the metabolic homeostasis in different tissues (1). FGF21 is elevated in pathological conditions such as obesity, insulin resistance, or fatty liver disease where an impairment of its signalling has been described (2). On the other hand, FGF21 analogues tested in overweight/obese patients with type 2 diabetes or NAFLD/NASH can reduce dyslipidaemia and steatosis, but improvements in glycaemic control or body weight were not globally restored (3). This suggests that pharmacologic effects of FGF21 are different from its physiological effects. In this Research Topic “FGF21 as a therapeutic target for obesity and insulin resistance: from rodent models to humans”, we include publications related to new advances involving FGF21, its signalling pathway, and its potential as a target to treat obesity