Effects Of Dietary AMP On Feed Intake And Lipid Metabolism And Its Mechanism In Mice

Feed intake is essential for animals to obtain nutrients to promote growth and development,but excessive energy intake will lead to overweight or obesity,which will seriously affect the health of animals.In the production of livestock,the excessive deposition of body fat not only wastes limited feed resources and increases the cost of breeding,but also reduces the meat quality.Nucleotides play an important role in animal metabolism.Our previous study has shown that dietary supplementation of nucleotides increased feed intake of sows during lactation.However,there is a lack of knowledge about the effects of single nucleotides on feed intake and lipid metabolism.The objective of the present study was to investigate the effects and mechanisms of dietary supplementation of adenosine 5’-monophosphate(AMP)on feed intake and lipid metabolism in mice.Experiment 1: Screening the type and concentration of nucleotide that can increase feed intake.Dietary supplementation with 0.1%,0.25% of AMP or uridine monophosphate,and statistics and analysis the cumulative feed intake and weekly body weight of the mice.The results showed that dietary supplementation with 0.1% AMP could significantly and stably increase the feed intake of mice(P<0.01).Experiment 2: Investigating the mechanism of AMP on feed intake and lipid metabolism in mice.Dietary supplementation with 0.1% AMP,and accurately record the feed intake and weekly body weight of mice.Before the end of the test,measuring the meal pattern,locomotor activity(beam breaks)and energy metabolism by metabolic cage;meanwhile,measuring the body composition by nuclear magnetic resonance and determining the temperature of brown adipose tissue(brown adipose tissue,BAT)by infrared detector,and conducting glucose tolerance test.At the end of the experiment,the blood of 0,2,4h after meals were collected to determine the nutrient substrate;the hypothalamus was collected to detect the expression of appetite peptide;and tissues such as fat,muscle,liver and other viscera were collected and weighed.Then determined the expression of genes and proteins related to lipid metabolism in BAT and determined the contents of AMP and adenosine in serum at 0,15,30,60 and 120 min after gavage of AMP by LC-MS.The results showed that:(1)The contents of AMP and adenosine in serum reached the maximum value at 60 min after gavage of AMP,and then began to decline.The dynamic curve showed that AMP could be absorbed into the blood and metabolized to produce adenosine in mice.(2)Dietary supplementation with AMP was significantly increased the cumulative feed intake of mice within 4 weeks of the trial(P<0.01).Meal pattern data showed that the AMP group had a tendency to shorten the mean intermeal bout length in mice(P=0.08),and increased the feed intake at night(P=0.05)and at day(P=0.10).In addition,the AMP group has reduced the blood glucose concentration at 4 h after meal(P<0.05)and up-regulated the Ag RP protein expression level in the hypothalamus(P<0.05),but no effect on POMC(P>0.10).(3)Although the diet had no effect on the body weight of the mice(P>0.10),the body composition in the AMP group was changed,which is increased the lean mass(P<0.01)and decreased the fat mass(P<0.05).Meanwhile,the AMP group has reduced the cell size in BAT and epididymal white adipose tissue(P<0.001),increased the rectal temperature(P<0.001)and BAT core temperature(P<0.05),and increased the energy expenditure of mice(P<0.05).Accordingly,the AMP group has reduced the m RNA expression of anti-lipid adenosine receptor A1(P<0.05),increased the m RNA expression levels of ATGL(P<0.05),LPL(P<0.05)and the regulation genes of fatty acid oxidation PPARα(P<0.01)and CPT-1β(P<0.05),and increased the m RNA and protein expression levels of UCP1(P<0.05)in BAT.In summary,dietary AMP showed a higher feed intake associated with an upregulation in the protein and m RNA level of Ag RP neurons in the hypothalamus attributed to a lower concentration of postprandial glucose in mice.Meanwhile,dietary AMP promoted lipid mobilization by up-regulating the lipolytic gene expression,and induced thermogenesis in BAT,which eventually leading to increase energy expenditure and prevention weight gain.