Insulin Resistance by Adiponectin Deficiency: Is the Action in Skeletal Muscle?

  1. Fredrik Karpe
  1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
  1. Corresponding author: Fredrik Karpe, fredrik.karpe{at}

Adiponectin is rapidly approaching its 20th anniversary, but it is still unclear how this apparently potent adipokine exerts its actions. The link to obesity and insulin resistance is obvious; the negative associations between plasma adiponectin concentrations and increasing fat mass or insulin sensitivity are reproducible and strong. The high abundance of adiponectin in plasma also implies a biological purpose. Adiponectin deficiency in mice gives rise to a reasonably mild insulin resistance upon high-fat feeding in most (13) but not all (4) models. Obviously, this fits well with the relative absence of adiponectin seen in insulin-resistant obese humans, but human monogenic causes of adiponectin deficiency are yet to be described. To further explore potential mechanisms of insulin resistance in response to adiponectin deficiency, Sweeney and colleagues (5) have used the most classic of endocrine approaches, i.e., to supplement a missing hormone or signal and observe the metabolic effect. The focus is on skeletal muscle and in particular the metabolomic patterns emerging in skeletal muscle after high-fat feeding and controlled adiponectin replenishment. Mice deficient for adiponectin were given a chow or high-fat diet …

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