Thoracic aortic aneurysms leading to type A dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. The first genes identified to cause TAAD were FBN1, TGFBR2, and TGFBR1. The identification and characterization of these genes suggested that increased TGF-beta signaling plays a role in pathogenesis. The recent discovery that mutations in the vascular smooth muscle cell (SMC)-specific beta-myosin (MYH11) and alpha-actin (ACTA2) can also cause this disorder has focused attention on the importance of the maintenance of SMC contractile function in preserving aortic structure and preventing TAAD.

Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here, we demonstrate that plasma asprosin crosses the blood-brain-barrier and directly activates orexigenic AgRP + neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic POMC + neurons in a GABA-dependent manner, resulting in appetite stimulation and a drive to accumulate adiposity and body weight. Genetic deficiency of asprosin in humans results in a syndrome characterized by low appetite and extreme leanness, which is phenocopied by mice carrying similar mutations, and one that can be fully rescued by Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

No abstract