title: Pioglitazone increases non-esterified fatty acid clearance in upper body obesity.
abstract: OBJECTIVE
  Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control.
  
  
  METHODS
  We measured plasma oleate concentration and flux ([(3)H]oleate), glucose kinetics ([6-(2)H(2)]glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for approximately 20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention.
  
  
  RESULTS
  Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02).
  
  
  CONCLUSIONS
  In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, 5-194 Joseph, 200 1st Street SW, Rochester, MN 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shadid
authors.forename: M D
authors.initials: MD
authors.lastname: Jensen
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D004038:Diet, Reducing; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy; D000077205:Pioglitazone; D012727:Sex Characteristics; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone