Adenosine and adenosine-5′-monophosphate ingestion ameliorates abnormal glucose metabolism in mice fed a high-fat diet

Abstract

BackgroundWe have previously reported that ingestion of adenosine (ADN) and adenosine-5′-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of non-obesity-associated insulin resistance. In this study, we investigated the effect of ADN and AMP ingestion on glucose metabolism in mice with high-fat diet-induced obesity.MethodsSeven-week-old C57BL/6 J mice were administered distilled water (as a control), 10 mg/L ADN, or 13 mg/L AMP via their drinking water for 14 or 25 weeks, during which they were fed a high-fat diet. Oral glucose tolerance test (OGTT) was conducted on 21-week-old mice fasted for 16 h. Insulin tolerance test (ITT) was performed on 22-week-old mice fasted for 3 h. Blood and muscle were collected for further analysis of serum parameters, gene and protein expression levels, respectively.ResultsGlucose metabolism in the ADN and AMP groups was significantly improved compared with the control. OGTT and ITT showed that ADN and AMP groups lower than control group. Furthermore, phosphorylation of AMP-activated protein kinase (AMPK) and mRNA levels of genes involved in lipid oxidation were enhanced in the skeletal muscle of ADN- and AMP-treated mice.ConclusionThese results indicate that ingestion of ADN or AMP induces activation of AMPK in skeletal muscle and mitigates insulin resistance in mice with high-fat diet-induced diabetes.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2367-6) contains supplementary material, which is available to authorized users.

Gut microbiota affects obesity susceptibility in mice through gut metabolites

“…This may be due to higher levels of circulating fatty acids and systemic inflammation, including fat and intestinal inflammation, in OP mice than in OR mice. As a result, OP mice exhibit higher serine phosphorylation of insulin receptor substrate 1 (IRS-1) and more severe insulin signaling blocking (Johnson and Olefsky, 2013 ; Ardiansyah et al, 2018 ). In addition, different metabolites produced by the gut microbiota of OP and OR mice, such as SCFAs and bile acids, enter the circulation and pass through G-protein coupled receptors (GPCRs), nuclear hormone receptors or host proteins post-translational modifications (such as lysine acetylation), thereby affecting whole-body insulin sensitivity (Johnson and Olefsky, 2013 ).…”

Dietary adenosine 5’-monophosphate supplementation increases food intake and remodels energy expenditure in mice

“…In the current study, dietary AMP supplementation was shown to increase the food intake by promoting the expression of AgRP and shortening the feeding interval, which is consistent with a previous study in aquatic ( 18 ), which reported that dietary 0.1% AMP supplementation contributed to the food intake of red sea bream ( 18 ). This can be attributed to the reason that the adenosine in food AMP can be absorbed into the body and reduce the concentration of glucose after meal ( 33 , 34 ). Studies have also shown that high levels of glucose after a meal reduce the AMP/ATP ratio in rats ( 35 ), or also reduce the level of AgRP in isolated hypothalamic cultures ( 36 ).…”

“…AMP is known as a purine nucleotide and participant in ATP metabolism. Studies have proved that AMP can be absorbed into the circulatory system and participate in metabolism ( 33 , 37 ). Here, we also found that AMP can be absorbed into the blood from the serum kinetic curve, which is consistent with the previous studies ( 33 ).…”

“…Studies have proved that AMP can be absorbed into the circulatory system and participate in metabolism ( 33 , 37 ). Here, we also found that AMP can be absorbed into the blood from the serum kinetic curve, which is consistent with the previous studies ( 33 ). A possible explanation for this phenomenon is that AMP is absorbed into the blood and enriched in the adipose tissue to play a subsequent regulatory role.…”

Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent

“…Adenosine is an important regulator of cellular metabolism that is produced from adenosine triphosphate (ATP) in the intracellular space [15] . Studies have suggested adenosine to mediate anti-inflammatory, anti-oxidative and energy homeostatic effects via enhancement of glucose uptake and inhibition of lipolysis [16] , [17] , [18] . Adenosine receptors, expressed on various cells including hepatocytes modulate metabolic and inflammatory processes such as glutathione synthesis, glucose production and liver control of renal Na+/water balance [19] .…”