Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the imm...Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.展开更多
Background: Since 1984 UK citizens have been advised to reduce total dietary fat intake to 30% of total energy and saturated fat intake to 10%. The National Institute of Clinical Excellence [NICE] suggests a further b...Background: Since 1984 UK citizens have been advised to reduce total dietary fat intake to 30% of total energy and saturated fat intake to 10%. The National Institute of Clinical Excellence [NICE] suggests a further benefit for Coronary Heart Disease [CHD] prevention by reducing saturated fat [SFA] intake to 6% - 7% of total energy and that 30,000 lives could be saved by replacing SFAs with Polyunsaturated fats [PUFAs]. Methods: 20 volumes of the Seven Countries Study, the seminal work behind the 1984 nutritional guidelines, were assessed. The evidence upon which the NICE guidance was based was reviewed. Nutritional facts about fat and the UK intake of fat are presented and the impact of macronutrient confusion on public health dietary advice is discussed. Findings: The Seven Countries study classified processed foods, primarily carbohydrates, as saturated fats. The UK government and NICE do the same, listing biscuits, cakes, pastries and savoury snacks as saturated fats. Processed foods should be the target of public health advice but not natural fats, in which the UK diet is deficient. With reference to the macro and micro nutrient composition of meat, fish, eggs, and dairy foods the article demonstrates that dietary trials cannot change one type of fat for another in a controlled study. Interpretation: The evidence suggests that processed food is strongly associated with the increase in obesity, diabetes, CHD, and other modern illness in our society. The macro and micro nutrients found in meat, fish, eggs and dairy products, are vital for human health and consumption of these nutritious foods should be encouraged.展开更多
The effects on finishing pigs(80-100 kg BW) fed diets supplemented with oil sources containing different ratios of unsaturated to saturated fatty acids(UFA:SFA ratio) were evaluated in 15 barrows and15 gilts(Duroc ...The effects on finishing pigs(80-100 kg BW) fed diets supplemented with oil sources containing different ratios of unsaturated to saturated fatty acids(UFA:SFA ratio) were evaluated in 15 barrows and15 gilts(Duroc × Large White × Landrace). Three experimental diets were evaluated using a randomized complete block design, with broken rice, soybean meal and rice bran as the main feedstuffs in the control diet. Diets 2 and 3 consisted of the control diet supplemented with 3% oil, with UFA:SFA ratios of 2.5:1 and 5:1, respectively. Overall, there was no significant difference(P> 0.05) found in the average daily gain(ADG) of the pigs fed the treatment diets; however, the pigs fed the control diet and diet 3 had better(P < 0.05) feed conversion ratios(FCR) than the pigs fed diet 2. The pigs fed diets 2 and 3, which were supplemented with oil at UFA:SFA ratios of 2.5:1 and 5:1, had greater(P < 0.05) average daily feed intakes(ADFI) than the pigs in the control group. Additionally, it was found that the gender of the pigs had an effect(P < 0.05) on the FCR. Interaction effects between the experimental diets and the gender of the pigs(P < 0.05) were found in the ADFI and FCR. There were no significance differences(P > 0.05)among the treatment groups with regard to the carcass quality of the pigs; however, it was found that the gilts had greater(P < 0.01) loin eye areas than the barrows fed diets 2 and 3 and the loin eye area of pig fed diet 2 was the largest(P < 0.05); In the case of the meat quality parameters, it was clearly found that the pigs fed the control diet had a greater(P < 0.05) lightness(L~*) in the meat colour, and the lowest cooking loss was found in the pigs fed the diet supplemented with fat containing the UFA:SFA ratio of 5:1.Overall, the dietary treatment did not significantly affect the drip loss, thawing loss and shear force of the pork. In conclusion, the supplementation of oil with UFA:SFA ratios of 2.5:1 and 5:1 has the potential to improve pork quality.展开更多
As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a...As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a mod-erate(10 weeks) and a prolonged(30 weeks) high fructose and saturated fatty acid(HFS) diet on plasma FA com-position in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to es-tablish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7)(decreased) and 20:4(n-6)(increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.展开更多
Hepatitis C virus(HCV)is a major cause of chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma(HCC)worldwide.Among the structural proteins of HCV,the HCV core protein has the ability to regulate gene transcr...Hepatitis C virus(HCV)is a major cause of chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma(HCC)worldwide.Among the structural proteins of HCV,the HCV core protein has the ability to regulate gene transcription,lipid metabolism,cell proliferation,apoptosis,and autophagy,all of which are closely related to the development of HCC.Transgenic mice carrying the HCV core gene exhibited age-dependent insulin resistance,hepatic steatosis,and HCC that resembled the clinical characteristics of chronic hepatitis C patients.Several dietary modifications,including calorie restriction and diets rich in saturated fatty acids,trans fatty acids,or cholesterol,were found to influence hepatic steatogenesis and tumorigenesis in HCV core gene transgenic mice.These strategies modulated hepatocellular stress and proliferation,in addition to hepatic fibrotic processes and the microenvironment,thereby corroborating a close interconnection between dietary habits and steatosis-related hepatocarcinogenesis.In this review,we summarize the findings obtained from mouse models transgenic for the HCV genome,with a special focus on HCV core gene transgenic mice,and discuss the mechanisms of steatogenesis and hepatocarcinogenesis induced by the HCV core protein and the impact of dietary habits on steatosis-derived HCC development.展开更多
In recent years,coconut oil has emerged as a potential‘miracle’food.Some media vehicles and health specialists assure that this fat is capable of promoting health benefits,such as weight reduction,cholesterol loweri...In recent years,coconut oil has emerged as a potential‘miracle’food.Some media vehicles and health specialists assure that this fat is capable of promoting health benefits,such as weight reduction,cholesterol lowering,prevention of cardiovascular diseases,and anti-inflammatory effect,among others.These claims are used to market the product and boost its sales by coconut oil companies.However,governmental regulatory agencies in many countries are still sceptical about the benefits obtained by the consumption of coconut oil due to its high-saturated fatty acid content.In light of such controversy,this review focused on analysing the published literature on the alleged health claims,in order to investigate if there is enough scientific evidence to support them.It was verified that the metabolism of lauric acid,the major fatty acid in coconut oil,remains unclear.Many studies reported that the product was not efficient in weight loss.Also,it has been reported that the consumption of coconut oil increased low-density lipoprotein cholesterol,consequently increasing the risk of cardiovascular diseases.In general,the studies present conflicting results and there is a lack of long-term human-based clinical trials.Therefore,as a saturated fat,coconut oil should be consumed with moderation and the health allegations should not be used to market the product,once they are not scientifically proven so far.展开更多
This study was to evaluate the effects of the supplementation of saturated fatty acids with different chain lengths on growth performance,intestinal morphology,epithelial cell proliferation,differentiation and apoptos...This study was to evaluate the effects of the supplementation of saturated fatty acids with different chain lengths on growth performance,intestinal morphology,epithelial cell proliferation,differentiation and apoptosis in weaned piglets.Thirty-two weaned piglets(Duroc×Landrace×Yorkshire,BW=7.81±0.26 kg)were weaned at 21 d and randomly assigned to 1 of 4 experimental treatments:(1)a basal diet(control);(2)control+0.3% butyrate(BT);(3)control+0.3%lauric acid(LA);(4)control+0.3% stearic acid(SA).All piglets were then slaughtered for tissue sampling after having been fed experimental diets for 28 d after weaning.Supplementation of BT increased the gain-to-feed ratio(G:F)(P<0.05)compared to piglets fed the control diet from 14 to 28 d.In addition,the villus height(VH)to crypt depth(CD)ratio(VH:CD ratio)of the ileum were higher in the BT and LA diets than that of the control diet(P<0.05).The SA-supplemented diet increased ileal VH(P<0.05),whereas the BT-supplemented diet increased jejunal CD(P<0.05).Compared to the control,diets supplemented with BT,LA,or SA all tended to increase jejunal proliferation(Ki67/crypt positive cells)(P=0.190);diets supplemented with BT or SA significantly increased the number of ki67-positive cells in the ileal crypt(P<0.05).Furthermore,in the jejunum,the protein expression of activated caspase 3 and villin were increased in piglets fed BT,LA,or SA diets compared to those on the control diet(P<0.05).In the ileum,compared with the control diet,the BT diet tended to increase the protein level of mammalian phosphorylation target of rapamycin(p-m TOR,P<0.10);LA or SA diets significantly increased p-m TOR protein expression(P<0.05).These results show that dietary supplementation of BT,LA,or SA promotes jejunal cell renewal in weaned piglets.At the same time,increased proliferation of ileal crypt cells by promoting p-m TOR expression has beneficial effects on ileal morphology in weaned piglets.展开更多
基金supported by the National Key Research and Development Program of China(No.2021YFA1201102)Henan Medical Science and Technology Joint Building Program(No.SBGJ202102132)+2 种基金Henan Province Youth Talent Promoting Project(No.2022HYTP047)the National Natural Science Foundation of China(Nos.82003255,82101385 and 82073231)Key Research and Development Project of Henan Province(No.232102311224)and First-Class Clinical Medicine Discipline Construction Talents Cultivation Project of Zhengzhou University.
文摘Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.
文摘Background: Since 1984 UK citizens have been advised to reduce total dietary fat intake to 30% of total energy and saturated fat intake to 10%. The National Institute of Clinical Excellence [NICE] suggests a further benefit for Coronary Heart Disease [CHD] prevention by reducing saturated fat [SFA] intake to 6% - 7% of total energy and that 30,000 lives could be saved by replacing SFAs with Polyunsaturated fats [PUFAs]. Methods: 20 volumes of the Seven Countries Study, the seminal work behind the 1984 nutritional guidelines, were assessed. The evidence upon which the NICE guidance was based was reviewed. Nutritional facts about fat and the UK intake of fat are presented and the impact of macronutrient confusion on public health dietary advice is discussed. Findings: The Seven Countries study classified processed foods, primarily carbohydrates, as saturated fats. The UK government and NICE do the same, listing biscuits, cakes, pastries and savoury snacks as saturated fats. Processed foods should be the target of public health advice but not natural fats, in which the UK diet is deficient. With reference to the macro and micro nutrient composition of meat, fish, eggs, and dairy foods the article demonstrates that dietary trials cannot change one type of fat for another in a controlled study. Interpretation: The evidence suggests that processed food is strongly associated with the increase in obesity, diabetes, CHD, and other modern illness in our society. The macro and micro nutrients found in meat, fish, eggs and dairy products, are vital for human health and consumption of these nutritious foods should be encouraged.
基金supported by Division of Research Administration, Naresuan University
文摘The effects on finishing pigs(80-100 kg BW) fed diets supplemented with oil sources containing different ratios of unsaturated to saturated fatty acids(UFA:SFA ratio) were evaluated in 15 barrows and15 gilts(Duroc × Large White × Landrace). Three experimental diets were evaluated using a randomized complete block design, with broken rice, soybean meal and rice bran as the main feedstuffs in the control diet. Diets 2 and 3 consisted of the control diet supplemented with 3% oil, with UFA:SFA ratios of 2.5:1 and 5:1, respectively. Overall, there was no significant difference(P> 0.05) found in the average daily gain(ADG) of the pigs fed the treatment diets; however, the pigs fed the control diet and diet 3 had better(P < 0.05) feed conversion ratios(FCR) than the pigs fed diet 2. The pigs fed diets 2 and 3, which were supplemented with oil at UFA:SFA ratios of 2.5:1 and 5:1, had greater(P < 0.05) average daily feed intakes(ADFI) than the pigs in the control group. Additionally, it was found that the gender of the pigs had an effect(P < 0.05) on the FCR. Interaction effects between the experimental diets and the gender of the pigs(P < 0.05) were found in the ADFI and FCR. There were no significance differences(P > 0.05)among the treatment groups with regard to the carcass quality of the pigs; however, it was found that the gilts had greater(P < 0.01) loin eye areas than the barrows fed diets 2 and 3 and the loin eye area of pig fed diet 2 was the largest(P < 0.05); In the case of the meat quality parameters, it was clearly found that the pigs fed the control diet had a greater(P < 0.05) lightness(L~*) in the meat colour, and the lowest cooking loss was found in the pigs fed the diet supplemented with fat containing the UFA:SFA ratio of 5:1.Overall, the dietary treatment did not significantly affect the drip loss, thawing loss and shear force of the pork. In conclusion, the supplementation of oil with UFA:SFA ratios of 2.5:1 and 5:1 has the potential to improve pork quality.
文摘As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a mod-erate(10 weeks) and a prolonged(30 weeks) high fructose and saturated fatty acid(HFS) diet on plasma FA com-position in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to es-tablish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7)(decreased) and 20:4(n-6)(increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.
基金This review has partially supported by JSPS Grants-in-Aid for Scientific Research(C)(KAKENHI,16K08616,16K08734,and 19K07383).
文摘Hepatitis C virus(HCV)is a major cause of chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma(HCC)worldwide.Among the structural proteins of HCV,the HCV core protein has the ability to regulate gene transcription,lipid metabolism,cell proliferation,apoptosis,and autophagy,all of which are closely related to the development of HCC.Transgenic mice carrying the HCV core gene exhibited age-dependent insulin resistance,hepatic steatosis,and HCC that resembled the clinical characteristics of chronic hepatitis C patients.Several dietary modifications,including calorie restriction and diets rich in saturated fatty acids,trans fatty acids,or cholesterol,were found to influence hepatic steatogenesis and tumorigenesis in HCV core gene transgenic mice.These strategies modulated hepatocellular stress and proliferation,in addition to hepatic fibrotic processes and the microenvironment,thereby corroborating a close interconnection between dietary habits and steatosis-related hepatocarcinogenesis.In this review,we summarize the findings obtained from mouse models transgenic for the HCV genome,with a special focus on HCV core gene transgenic mice,and discuss the mechanisms of steatogenesis and hepatocarcinogenesis induced by the HCV core protein and the impact of dietary habits on steatosis-derived HCC development.
文摘In recent years,coconut oil has emerged as a potential‘miracle’food.Some media vehicles and health specialists assure that this fat is capable of promoting health benefits,such as weight reduction,cholesterol lowering,prevention of cardiovascular diseases,and anti-inflammatory effect,among others.These claims are used to market the product and boost its sales by coconut oil companies.However,governmental regulatory agencies in many countries are still sceptical about the benefits obtained by the consumption of coconut oil due to its high-saturated fatty acid content.In light of such controversy,this review focused on analysing the published literature on the alleged health claims,in order to investigate if there is enough scientific evidence to support them.It was verified that the metabolism of lauric acid,the major fatty acid in coconut oil,remains unclear.Many studies reported that the product was not efficient in weight loss.Also,it has been reported that the consumption of coconut oil increased low-density lipoprotein cholesterol,consequently increasing the risk of cardiovascular diseases.In general,the studies present conflicting results and there is a lack of long-term human-based clinical trials.Therefore,as a saturated fat,coconut oil should be consumed with moderation and the health allegations should not be used to market the product,once they are not scientifically proven so far.
基金supported by National Natural Science Foundation of China(Grant No.32130099)Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process open fund projects(Grant No.ISA2020113)。
文摘This study was to evaluate the effects of the supplementation of saturated fatty acids with different chain lengths on growth performance,intestinal morphology,epithelial cell proliferation,differentiation and apoptosis in weaned piglets.Thirty-two weaned piglets(Duroc×Landrace×Yorkshire,BW=7.81±0.26 kg)were weaned at 21 d and randomly assigned to 1 of 4 experimental treatments:(1)a basal diet(control);(2)control+0.3% butyrate(BT);(3)control+0.3%lauric acid(LA);(4)control+0.3% stearic acid(SA).All piglets were then slaughtered for tissue sampling after having been fed experimental diets for 28 d after weaning.Supplementation of BT increased the gain-to-feed ratio(G:F)(P<0.05)compared to piglets fed the control diet from 14 to 28 d.In addition,the villus height(VH)to crypt depth(CD)ratio(VH:CD ratio)of the ileum were higher in the BT and LA diets than that of the control diet(P<0.05).The SA-supplemented diet increased ileal VH(P<0.05),whereas the BT-supplemented diet increased jejunal CD(P<0.05).Compared to the control,diets supplemented with BT,LA,or SA all tended to increase jejunal proliferation(Ki67/crypt positive cells)(P=0.190);diets supplemented with BT or SA significantly increased the number of ki67-positive cells in the ileal crypt(P<0.05).Furthermore,in the jejunum,the protein expression of activated caspase 3 and villin were increased in piglets fed BT,LA,or SA diets compared to those on the control diet(P<0.05).In the ileum,compared with the control diet,the BT diet tended to increase the protein level of mammalian phosphorylation target of rapamycin(p-m TOR,P<0.10);LA or SA diets significantly increased p-m TOR protein expression(P<0.05).These results show that dietary supplementation of BT,LA,or SA promotes jejunal cell renewal in weaned piglets.At the same time,increased proliferation of ileal crypt cells by promoting p-m TOR expression has beneficial effects on ileal morphology in weaned piglets.
