Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats.
OBJECTIVE
Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats.


METHODS
In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old.


RESULTS
Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.


CONCLUSIONS
From the results obtained, beneficial effects of metformin on visceral fat reduction has been demonstrated probably through a mechanism for a potential shift of fuel resource into fat oxidation and an upregulation of adaptive thermogenesis independent of an anorexigenic effect of this drug.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Ichiro
I
Tokubuchi
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Yuji
Y
Tajiri
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Shimpei
S
Iwata
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Kento
K
Hara
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Nobuhiko
N
Wada
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Toshihiko
T
Hashinaga
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Hitomi
H
Nakayama
Institute of Animal Experimentation, Kurume University School of Medicine, Kurume, Japan.
Hiroharu
H
Mifune
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Kentaro
K
Yamada
D000328:Adult; D000818:Animals; D015415:Biomarkers; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology* / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects*; D019518:Postprandial Period; D051381:Rats
D015415:Biomarkers; D005227:Fatty Acids; D008687:Metformin