Date Published: February 3, 2017
Publisher: Public Library of Science
Author(s): Ichiro Tokubuchi, Yuji Tajiri, Shimpei Iwata, Kento Hara, Nobuhiko Wada, Toshihiko Hashinaga, Hitomi Nakayama, Hiroharu Mifune, Kentaro Yamada, M. Faadiel Essop.
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.
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.
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.
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.
In the 2013 issue of the International Diabetes Federation (IDF) Diabetes Atlas, the prevalence of diabetes in the Western Pacific (WP) Region was reported to be 8.6% in 2013, or 138 million adults, and was estimated to rise to 11.1%, or 201 million adults, in 2035 . Type 2 diabetes accounts for 95% of the diabetes in Japanese diabetic patients and the number of patients is still increasing along with the number of overweight/obesity individuals reflecting environmental factors, including overeating and a lack of exercise. However, it is of interest that the prevalence of diabetes in Asian people is almost the same as that in Caucasian despite of their much lower BMI. The reason is probably genetic and is likely due to their lower capacity for insulin secretion in comparison to Caucasian’s . Asian people, including Japanese, are therefore thought be much more likely to be affected by diabetes than people in western countries in the era of satiety.
The principal results of the present study are as follows. First, lactate and pyruvate concentrations increased, reflecting the enhancement of anaerobic glycolysis by metformin treatment . Second, metformin decreased RQ, suggesting that fat oxidation was accelerated by this drug. Third, metformin reduced visceral fat in rats, independent of its anorexigenic effect. Finally, metformin was found to upregulate enzymes related to fat oxidation and adaptive thermogenesis, in line with a lower RQ and visceral fat mass reduction.