Progranulin, a New Adipokine at the Crossroads of Metabolic Syndrome, Diabetes, Dyslipidemia and Hypertension.

Abstract

Progranulin is a multifunctional regulatory protein with growth-promoting, neuroprotective and antiinflammatory activities. Recent studies indicate that progranulin is one of the adipose tissue hormones (adipokines). Progranulin expression in visceral adipose tissue and circulating progranulin concentration are increased in obesity and hyperprogranulinemia is involved in the pathogenesis of obesity-associated insulin resistance. Progranulin impairs insulin signaling and reduces insulin-induced glucose uptake both in vitro and in vivo whereas progranulin deficiency protects from high fat diet-induced insulin resistance. Several studies, including some prospective ones, have demonstrated the association between high progranulin and type 2 diabetes and its complications such as nephro- and retinopathy as well as non-alcoholic fatty liver disease. It is quite well established that progranulin contributes to insulin resistance and resulting deterioration of carbohydrate metabolism. In addition, progranulin may be associated with the development of diabetic microangiopathy, fatty liver disease and possibly with the increased risk of cancer in subjects with the metabolic syndrome. On the other hand, progranulin augments vasorelaxation, inhibits inflammatory reaction, is neuroprotective and reduces ischemiareperfusion injury. Progranulin has both detrimental and beneficial effects. More clinical studies including prospective ones are needed to clarify the role of progranulin in obesity-associated pathologies such as diabetes, hyperlipidemia, hypertension and atherosclerosis.