Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free...Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.展开更多
The macronutrient composition of food supply in China has altered dramatically in the past 70 years.Fat(oil)has increased more than 4.2-times while the carbohydrate content has declined by 34%.Vegetable oils are the m...The macronutrient composition of food supply in China has altered dramatically in the past 70 years.Fat(oil)has increased more than 4.2-times while the carbohydrate content has declined by 34%.Vegetable oils are the major component of the fat intake and since these oils are rich in linoleic acid,there has been a significant rise in the consumption of this fatty acid(as much as a 4-fold rise).Linoleic acid has essential functions in the body in skin and as a precursor of prostaglandins and related compounds.The current intakes of linoleic acid are well in excess of the minimum requirements.In this review,the effects of a food supply rich in linoleic acid on pain in arthritis and headache,non-alcoholic fatty liver and neural function are explored,with emphasis on lipid mediators derived from linoleic acid and other long chain polyunsaturated fatty acids.The current world food systems have created an imbalance of dietary linoleic acid in relation to n-3 polyunsaturated fatty acids,and an imbalance in the lipid mediators derived from these polyunsaturated fatty acids which may be contributing to sub-optimal health status.展开更多
Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excess...Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excessive LA on colon cancer in human is not conclusive,making it difficult to make dietary recommendations for optimal intake of LA.Understanding the molecular mechanisms of LA on colon tumorigenesis could help to clarify its health effect,and facilitate development of mechanismbased strategies for preventing colon cancer.Recent studies show that the previously unappreciated cytochrome P450 monooxygenase-mediated eicosanoid pathway is upregulated in colon cancer and plays critical roles in its pathogenesis,and could contribute to the effects of dietary LA,as well asω-3 fatty acids,on colon tumorigenesis.In this review,we will discuss recent studies about the roles of cytochrome P450 monooxygenases in fatty acid metabolism and its roles in colonic inflammation and colon cancer,and how this information could help us to clarify the health impacts of dietary fatty acids.展开更多
基金Supported by Grant from Department of Education of Liaoning Province (2008810)
文摘Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.
文摘The macronutrient composition of food supply in China has altered dramatically in the past 70 years.Fat(oil)has increased more than 4.2-times while the carbohydrate content has declined by 34%.Vegetable oils are the major component of the fat intake and since these oils are rich in linoleic acid,there has been a significant rise in the consumption of this fatty acid(as much as a 4-fold rise).Linoleic acid has essential functions in the body in skin and as a precursor of prostaglandins and related compounds.The current intakes of linoleic acid are well in excess of the minimum requirements.In this review,the effects of a food supply rich in linoleic acid on pain in arthritis and headache,non-alcoholic fatty liver and neural function are explored,with emphasis on lipid mediators derived from linoleic acid and other long chain polyunsaturated fatty acids.The current world food systems have created an imbalance of dietary linoleic acid in relation to n-3 polyunsaturated fatty acids,and an imbalance in the lipid mediators derived from these polyunsaturated fatty acids which may be contributing to sub-optimal health status.
基金This research is supported by a new faculty start-up from the University of Massachusetts Amherst,USDA NIFA2016-67017-24423,USDA NIFA 2019-67017-29248,USDA/HatchMAS00492,and NIH/NCIR03 CA218520(to G.Z.).
文摘Human consumption of linoleic acid(LA,18:2ω-6,abundant in vegetable oils)is very high.Animal experiments showed that excessive LA intake increased azoxymethane-induced colon tumorigenesis,however,the impact of excessive LA on colon cancer in human is not conclusive,making it difficult to make dietary recommendations for optimal intake of LA.Understanding the molecular mechanisms of LA on colon tumorigenesis could help to clarify its health effect,and facilitate development of mechanismbased strategies for preventing colon cancer.Recent studies show that the previously unappreciated cytochrome P450 monooxygenase-mediated eicosanoid pathway is upregulated in colon cancer and plays critical roles in its pathogenesis,and could contribute to the effects of dietary LA,as well asω-3 fatty acids,on colon tumorigenesis.In this review,we will discuss recent studies about the roles of cytochrome P450 monooxygenases in fatty acid metabolism and its roles in colonic inflammation and colon cancer,and how this information could help us to clarify the health impacts of dietary fatty acids.
