Metformin inhibits catecholamine-stimulated lipolysis in obese, hyperinsulinemic, hypertensive subjects in subcutaneous adipose tissue: an in situ microdialysis study.
OBJECTIVE
Metformin has been reported to decrease the plasma concentrations of non-esterified fatty acids in Type 2 diabetic subjects. This study investigated the effects of metformin on basal and catecholamine-stimulated lipolysis in abdominal subcutaneous adipose tissue of obese, hyperinsulinaemic, hypertensive subjects.


METHODS
Fourteen subjects with severe obesity (12 female, twomale, age 35.4 +/- 4 years, body mass index 48.2 +/- 2 kg/m2, body fat mass 63.3 +/- 5 kg) were recruited. Glycerol and lactate concentrations were determined in the presence of metformin and after administration of catecholamines using microdialysis. Simultaneously, blood flow was assessed with the ethanol escape method.


RESULTS
Glycerol release was lowered by metformin during the 3-h experiment (P<0.01). The lipolytic activity of catecholamines was suppressed when adipose tissue was pre-treated with metformin (P<0.001). Lactate concentration increased after application of metformin (P<0.01) and catecholamines (P<0.001). Blood flow was decreased in the presence of adrenaline (P < 0.01), but this effect was abolished by metformin.


CONCLUSIONS
The present data demonstrate the effects of metformin on lipolysis in subcutaneous adipose tissue in vivo. In the large body fat mass of obese subjects, a reduction of lipolysis in adipose tissue may contribute to a decrease of VLDL synthesis in the liver resulting in a lowered plasma triglyceride concentration.
Flechtner-Mors
M
M
Department of Internal Medicine, University of Ulm, Germany. marion.mors@medizin.uni-ulm.de
Ditschuneit
H H
HH
Jenkinson
C P
CP
Alt
A
A
Adler
G
G
D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D017097:Electric Impedance; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D017551:Microdialysis; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000150:complications / Q000378:metabolism*
D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin; D005990:Glycerol; D009638:Norepinephrine; D004837:Epinephrine