Just Along for the Ride?
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Adiponectin is the most adipocyte-specific of all secretory factors described to date. Despite its exclusive expression at the level of the fat cell, adiponectin concentrations in plasma are generally inversely proportional to fat mass.1,2 More detailed studies reveal that it is not fat mass, but rather fat quality that is the driving force for adiponectin expression. Comparing metabolically healthy and metabolically unhealthy obese individuals, the metabolically healthy individuals display higher levels of adiponectin despite identical body mass indices.3,4 This reflects the close relationship between adiponectin and insulin sensitivity. Mouse models that maintain high adiponectin levels similar to lean mice, despite gaining weight,5,6 retain full metabolic flexibility. Positive changes in adiponectin levels are also a reflection of therapeutic improvements in systemic insulin sensitivity, such as on exposure to a PPARγ (peroxisome proliferator-activated receptor gamma) agonists.7 We and many others concluded, therefore, that adiponectin levels are excellent integrators of adipose tissue health and systemic metabolic flexibility,8 including as a direct driving force for positive effects exerted on cardiovascular disease states.9
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Borges et al10 now undertook a Mendelian randomization study using data from several different genome-wide association studies consortia. The authors used …