Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats

Abstract

ObjectiveMetformin 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.MethodsIn 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.ResultsPost-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.ConclusionFrom 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.

Of mice and men: Is there a future for metformin in the treatment of hepatic steatosis?

“…These findings suggest that either (a) metformin does not robustly activate AMPK, or (b) metformin increases FAO independently of AMPK. Other studies have reported elevated gene expression of markers of FAO and increased mitochondrial biogenesis in mice fed an HFD and treated with metformin, which would potentially lead to greater oxidative capacity. Metformin has also been shown to prevent HFD‐induced loss of PPAR‐α expression in mice, which may be indicative of enhanced FAO .…”

“…Metformin has also been shown to prevent HFD‐induced loss of PPAR‐α expression in mice, which may be indicative of enhanced FAO . Tokubuchi et al investigated the effects of 2 weeks' treatment with metformin on energy metabolism in healthy people and people with T2DM and concluded that metformin reduced fasting respiratory quotient, suggesting a shift in the utilisation of fat as a fuel after metformin treatment, which may be indicative of enhanced FAO. However, metformin also increased the postprandial respiratory quotient in both healthy and T2DM groups, suggesting enhanced aerobic glycolysis, which does not support enhanced FAO via AMPK …”

“…However, metformin also increased the postprandial respiratory quotient in both healthy and T2DM groups, suggesting enhanced aerobic glycolysis, which does not support enhanced FAO via AMPK. 60…”

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

“…Metformin's beneficial effects on energy metabolism include enhanced activity of carnitine palmitoyltransferase 1, an essential component of mitochondrial fatty acid oxidation. 48 Metformin also promoted restoration of mitochondrial membrane potential and reversal of mutationassociated alterations in energy metabolism in a model of Parkinson disease 49 and contributed toward the restoration of cellular energy by activating adenosine monophosphate-activated protein kinase. 50 Our preliminary data have indicated that the coadministration of metformin with cisplatin prevents the neuronal mitochondrial dysfunction that results from cisplatin treatment in a mouse model of CIPN.…”

“…Although the exact mechanisms underlying these protective effects need to be delineated, it is likely that metformin acts via modulation of mitochondria‐dependent cellular metabolism. Metformin's beneficial effects on energy metabolism include enhanced activity of carnitine palmitoyltransferase 1, an essential component of mitochondrial fatty acid oxidation . Metformin also promoted restoration of mitochondrial membrane potential and reversal of mutation‐associated alterations in energy metabolism in a model of Parkinson disease and contributed toward the restoration of cellular energy by activating adenosine monophosphate‐activated protein kinase .…”