Il processo coinvolge una proteina chiamata PGC-1beta
Alcuni ricercatori del Dana-Farber Cancer Institute di Boston hanno identificato un meccanismo molecolare nel fegato che spiega, per la prima volta, come il consumo di cibi ricchi di grassi saturi e acidi grassi idrogenati causi livelli elevati di colesterolo e trigliceridi nel sangue e aumenti il rischio di attacco cardiaco e di alcuni tipi di tumore. In un articolo pubblicato sul numero del 28 gennaio della rivista "Cell", Bruce Spiegelman e colleghi scrivono che gli effetti dannosi dei grassi saturi e idrogenati vengono messi in moto nelle cellule del fegato da un interruttore biochimico, o co-attivatore, chiamato PGC-1beta.
Finora agli scienziati mancava una spiegazione dettagliata del modo in cui i grassi saturi e idrogenati provocano un aumento del colesterolo e dei trigliceridi nel sangue. Gli indizi suggerivano che fosse coinvolto il fegato, che è responsabile della sintesi di queste sostanze nel corpo, ma la catena molecolare degli eventi dal consumo di cibi grassi fino all'accumulo di colesterolo nel sangue era sconosciuta.
"Abbiamo trovato l'anello mancante, - spiega Spiegelman - un meccanismo tramite il quale agiscono i grassi saturi e idrogenati". Quando viene attivata dai grassi dannosi, la proteina PGC1-beta alterna il metabolismo del fegato attraverso una cascata di segnali biochimici. Il risultato è un aumento improvviso della produzione di lipoproteine a bassissima densità (VLDL) - precursori delle lipoproteine a bassa densità (LDL), quelle del cosiddetto "colesterolo cattivo" - che vengono rilasciate nel flusso sanguigno.
J. Lin, R. Yang, P.T. Tarr, P.-H. Wu, C. Handschin, S. Li, W. Yang, L. Pei, M. Uldry, P. Tontonoz, C.B. Newgard, B.M. Spiegelman, “Hyperlipidemic Effects of Dietary Saturated Fats Mediated Through PGC-1b Coactivation of SREBP”. Cell (28 gennaio 2005).
Showing posts with label Calorie. Show all posts
Showing posts with label Calorie. Show all posts
Saturday, December 17, 2011
DFCI - Scientists discover molecular "switch" in liver that triggers harmful effects of saturated and trans fats - 2005 Press Releases
DFCI - Scientists discover molecular "switch" in liver that triggers harmful effects of saturated and trans fats - 2005 Press Releases.
Dana-Farber Cancer Institute researchers have identified a molecular mechanism in the liver that explains, for the first time, how consuming foods rich in saturated fats and trans-fatty acids causes elevated blood levels of cholesterol and triglycerides and increases one's risk of heart disease and certain cancers.
In the Jan. 28 issue of Cell, scientists led by Bruce Spiegelman, PhD, report that the harmful effects of saturated and trans fats are set in motion by a biochemical switch, or co-activator, in liver cells called PGC-1beta.
Until now, scientists lacked a detailed explanation of how saturated and trans fats caused an increase in blood cholesterol and triglycerides, while diets high in unsaturated and polyunsaturated fats did not. Evidence pointed to the liver, which is responsible for the body's synthesis of triglycerides and cholesterol, but the molecular chain of events from eating fats to the buildup of cholesterol and triglycerides in the blood were unknown.
"What we have found is a missing link, a mechanism by which saturated fats and trans fats can do their dirty work," said Spiegelman, who carries out basic research on fat cells and metabolic pathways in diabetes and cancer at Dana-Farber. "It offers the opportunity to try to understand what makes these fatty acids so deleterious, and what we need to avoid."
Moreover, it is possible that in the future, drug therapy might be used to "turn down" the mechanism, decreasing cholesterol levels and heart disease risk, explained Spiegelman, who is also a professor of cell biology at Harvard Medical School.
Saturated fats are found in fatty cuts of meat, whole-milk dairy products, butter, and palm and coconut oils; they are associated with higher risk of coronary disease. The healthier polyunsaturated fats are those that remain liquid at room temperature, such as various types of vegetable oils.
Trans-unsaturated fatty acids, or trans fats, are artificially produced solid fats used in shortening and margarine, baked goods, and the oils used to cook french fries and other fast food. Studies have shown that trans fats not only raise LDL levels in the bloodstream but lower high-density lipoproteins (HDL, or "good" cholesterol) and may have even stronger adverse effects than do saturated fats.
The researchers report that when activated by harmful fats, PGC-1beta alters liver metabolism through a cascade of biochemical signals. The result is an upsurge in the liver's production of very low-density lipoprotein (VLDL) cholesterol, the precursor of low-density lipoprotein (LDL) cholesterol (known as the "bad" form of cholesterol) and triglycerides – another fatty substance – that are secreted into the bloodstream.
PGC-1beta belongs to a specific family of co-activators, proteins that interact with other proteins to turn genes on and off and adjust their activity, like a dimmer switch that varies the brightness of a light. Co-activators join with other regulatory proteins called transcription factors in controlling the expression of genes. Spiegelman and Jiandie Lin, PhD, the paper's lead author and a researcher at Dana-Farber, have previously discovered the PGC-1 co-activator family and several of its biochemical activities.
The Dana-Farber researchers made the discovery in searching for the function of PGC-1beta co-activator that was isolated in 2002. Experiments including the measurement of gene activity by microarrays showed that saturated and trans fats caused greater activity of the gene that makes PGC-1beta co-activator than did unsaturated fats.
The research also showed that when the fats triggered PGC-1beta, the co-activator interacted physically and turned up the function of sterol responsive element binding proteins. These important parts of the mechanism activate many key genes of lipid biosynthesis involving the pathways of cholesterol and triglycerides; these genes directed the liver to manufacture more cholesterol, which it does in the form of very low-density lipoproteins. The investigators noted that in mice fed high-fat diets, the PCG-1beta mechanism actually decreased cholesterol in the liver while increasing it in the bloodstream.
"Before this report, it wasn't clear what the differences were between saturated fats and unsaturated fats in their ability to raise cholesterol blood levels," commented Jeffrey Flier, MD, an obesity specialist at Beth Israel Deaconess Medical Center. "These are important findings in a long-established area of medicine."
Grants from the National Institutes of Health supported the research.
The paper's other authors are based at Dana-Farber, Duke University Medical Center, and the University of California, Los Angeles.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
(Note: A copy of the paper can be obtained through Cell's press office (617) 397-2879) or via EurekAlert! (http://www.eurekalert.org/jrnls/cell/pages/index.php). Reporters who do not have access to EurekAlert! can e-mail Heidi Hardman at Cell, hhardman@cell.com, to request a PDF of the article.)
Dana-Farber Cancer Institute researchers have identified a molecular mechanism in the liver that explains, for the first time, how consuming foods rich in saturated fats and trans-fatty acids causes elevated blood levels of cholesterol and triglycerides and increases one's risk of heart disease and certain cancers.
In the Jan. 28 issue of Cell, scientists led by Bruce Spiegelman, PhD, report that the harmful effects of saturated and trans fats are set in motion by a biochemical switch, or co-activator, in liver cells called PGC-1beta.
Until now, scientists lacked a detailed explanation of how saturated and trans fats caused an increase in blood cholesterol and triglycerides, while diets high in unsaturated and polyunsaturated fats did not. Evidence pointed to the liver, which is responsible for the body's synthesis of triglycerides and cholesterol, but the molecular chain of events from eating fats to the buildup of cholesterol and triglycerides in the blood were unknown.
"What we have found is a missing link, a mechanism by which saturated fats and trans fats can do their dirty work," said Spiegelman, who carries out basic research on fat cells and metabolic pathways in diabetes and cancer at Dana-Farber. "It offers the opportunity to try to understand what makes these fatty acids so deleterious, and what we need to avoid."
Moreover, it is possible that in the future, drug therapy might be used to "turn down" the mechanism, decreasing cholesterol levels and heart disease risk, explained Spiegelman, who is also a professor of cell biology at Harvard Medical School.
Saturated fats are found in fatty cuts of meat, whole-milk dairy products, butter, and palm and coconut oils; they are associated with higher risk of coronary disease. The healthier polyunsaturated fats are those that remain liquid at room temperature, such as various types of vegetable oils.
Trans-unsaturated fatty acids, or trans fats, are artificially produced solid fats used in shortening and margarine, baked goods, and the oils used to cook french fries and other fast food. Studies have shown that trans fats not only raise LDL levels in the bloodstream but lower high-density lipoproteins (HDL, or "good" cholesterol) and may have even stronger adverse effects than do saturated fats.
The researchers report that when activated by harmful fats, PGC-1beta alters liver metabolism through a cascade of biochemical signals. The result is an upsurge in the liver's production of very low-density lipoprotein (VLDL) cholesterol, the precursor of low-density lipoprotein (LDL) cholesterol (known as the "bad" form of cholesterol) and triglycerides – another fatty substance – that are secreted into the bloodstream.
PGC-1beta belongs to a specific family of co-activators, proteins that interact with other proteins to turn genes on and off and adjust their activity, like a dimmer switch that varies the brightness of a light. Co-activators join with other regulatory proteins called transcription factors in controlling the expression of genes. Spiegelman and Jiandie Lin, PhD, the paper's lead author and a researcher at Dana-Farber, have previously discovered the PGC-1 co-activator family and several of its biochemical activities.
The Dana-Farber researchers made the discovery in searching for the function of PGC-1beta co-activator that was isolated in 2002. Experiments including the measurement of gene activity by microarrays showed that saturated and trans fats caused greater activity of the gene that makes PGC-1beta co-activator than did unsaturated fats.
The research also showed that when the fats triggered PGC-1beta, the co-activator interacted physically and turned up the function of sterol responsive element binding proteins. These important parts of the mechanism activate many key genes of lipid biosynthesis involving the pathways of cholesterol and triglycerides; these genes directed the liver to manufacture more cholesterol, which it does in the form of very low-density lipoproteins. The investigators noted that in mice fed high-fat diets, the PCG-1beta mechanism actually decreased cholesterol in the liver while increasing it in the bloodstream.
"Before this report, it wasn't clear what the differences were between saturated fats and unsaturated fats in their ability to raise cholesterol blood levels," commented Jeffrey Flier, MD, an obesity specialist at Beth Israel Deaconess Medical Center. "These are important findings in a long-established area of medicine."
Grants from the National Institutes of Health supported the research.
The paper's other authors are based at Dana-Farber, Duke University Medical Center, and the University of California, Los Angeles.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
(Note: A copy of the paper can be obtained through Cell's press office (617) 397-2879) or via EurekAlert! (http://www.eurekalert.org/jrnls/cell/pages/index.php). Reporters who do not have access to EurekAlert! can e-mail Heidi Hardman at Cell, hhardman@cell.com, to request a PDF of the article.)
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